Hemodialysis.com Kidney Disease Interviews March 24 2013

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Hemodialysis research, author interviews, dialysis updates and information on chronic kidney disease and end stage renal failure.

Editor: Marie Benz, [email protected]

March 24 2013

For Informational Purposes Only: Not for Specific Medical Advice.

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Hemodialysis.com InterviewsMarch 24 2013

For Informational Purposes Only. Not for Specific Medical Advice


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Effects of Cholecalciferol on Functional, Biochemical, Vascular, and Quality of Life Outcomes in Hemodialysis PatientsHemodialysis.com Interview with Dr. Grahame J. ElderClinical A/Professor (Sydney and UNDA)Department of Renal Medicine,

Westmead HospitalOsteoporosis and Bone Biology Programme, Garvan Institute Sydney

• Hemodialysis.com: What are the main findings of the study?• Dr. Elder: This study is one of very few randomized controlled trials in patients on hemodialysis.assessing

the effect of cholecalciferol use to improve levels of 25-hydroxyvitamin D After 6 months, patients treated with cholecalciferol had higher values of both 25-hydroxyvitamin D and calcitriol (1,25-dihydroxyvitamin D), the most active form of vitamin D than patients treated with placebo. This was achieved without adverse effects on calcium or phosphorus levels.

• However, after 6 months treatment we could not discern any effect of supplementation on muscle strength or function, pulse wave velocity (an indicator of vascular stiffness and surrogate for vascular calcification) or on quality of life Whether this is because the period of supplementation was too short, the patients selected had higher values of 25-hydroxyvitamin D than many patients on dialysis, or because cholecalciferol will not influence these outcomes are questions that cannot be answered by our data.

• Hemodialysis.com: Were any of the findings unexpected?• Dr. Elder: We were interested to see that phosphorus levels and phosphate binder use were lower at 6

months in patients treated with cholecalciferol. Also the rise in the TRAcP-5b, an osteoclast marker, was a surprise because we had thought that if anything, cholecalciferol might reduce parathyroid hormone levels, osteoclast activation and bone turnover. However, recent human and animal studies have reported that both osteoblasts and osteoclasts can metabolize 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D, so perhaps this might have been expected. We were of course surprised to find no effect on muscle strength, which we had designated the primary outcome for the study, or on functional testing,


http://hemodialysis.com/effects-of-cholecalciferol-on-functional-biochemical-vascular-and-quality-of-life-outcomes-in-hemodialysis-patients/
















Effects of Cholecalciferol on Functional, Biochemical, Vascular, and Quality of Life Outcomes in Hemodialysis PatientsHemodialysis.com Interview with Dr. Grahame J. ElderClinical A/Professor (Sydney and UNDA)

Department of Renal Medicine, Westmead HospitalOsteoporosis and Bone Biology Programme, Garvan Institute Sydney(cont)

• Hemodialysis.com: What should clinicians and patients take away from this study?• Dr. Elder: Cholecalciferol treatment increased levels of 25-hydroxyvitamin D in patients on hemodialysis. Patients

receiving this treatment have higher levels of calcitriol than those who do not and the treatment is unlikely to cause adverse effects on levels of calcium or phosphorus. The baseline data indicating positive associations of 25-hydroxyvitamin D and functional testing and an inverse relationship or 25-hydroxyvitamin D to pulse wave velocity, although of course this does not prove any benefit will derive from treatment. But on the other hand, it certainly supports the contention that treatment will do no harm.

• Hemodialysis.com: What recommendations do you have for future research as a result of your study?• Dr. Elder: At baseline we found positive associations of 25-hydroxyvitamin D values and distance covered in a 6 minute

walk and an inverse relationship of 25-hydroxyvitamin D values and pulse wave velocity. These findings are consistent with associations reported in a number of other studies, so it remains possible that longer studies, or studies recruiting patients with lower levels of vitamin D in the ‘deficient’ range, might find that functional tests and vascular stiffness improve over time. A number of cross sectional and some longitudinal studies have now reported that hemodialysis patients with higher 25-hydroxyvitamin D levels or calciferol (cholecalciferol or ergocalciferol) supplementation have higher levels of calcitriol as we also reported In turn, improved calcitriol levels may have positive influences on vascular tissue and cardiovascular outcomes, providing hypercalcemia and hyperphosphatemia are avoided. A longer and much larger study to assess the influence of calciferol supplementation on cardiovascular events and mortality is long overdue.

• Citation:• Effects of Cholecalciferol on Functional, Biochemical, Vascular, and Quality of Life Outcomes in Hemodialysis Patients• Nathan A. Hewitt, Alicia A. O’Connor, Denise V. O’Shaughnessy, and Grahame J. Elder• CJASN CJN.02840312; published ahead of print March 14, 2013, doi:10.2215/CJN.02840312








Demographic, metabolic, and blood pressure characteristics of living kidney donors spanning five decades.Hemodialysis.com Author Interview with Sandra J. Taler, M.D. Consultant, Division of Nephrology/Hypertension

Associate Professor of Medicine | College of Medicine |Mayo Clinic | 200 First Street SW | Rochester, MN 55905

• Hemodialysis.com: What are the main findings of the study?

• Dr. Taler: We reviewed the medical records of all living kidney donors (8951 total) from 3 large transplant centers (Mayo Clinic, University of Alabama in Birmingham and University of Minnesota) since the beginning of living donation in 1963 through 2007.

• We examined trends in the metabolic profile of accepted living donors by quartiles of this 44 year timespan. We saw a trend to higher donor age with fewer donors in their 20s but only 4% of donors were older than age 60 years at the time of donation. Using a consistent definition for hypertension, we found the percentage of donors with hypertension remained low and was stable over time. We did find an increasing proportion of donors were obese or had glucose intolerance in the more recent time quartiles however most had mild elevations in glucose that met acceptance criteria. There was greater tolerance for one or more metabolic abnormalities in older donors but the percentage of older donor remained quite low.

• Hemodialysis.com: Were any of the findings unexpected?

• Dr. Taler: Yes. We thought we might find a higher rate of hypertensive donors accepted in the more recent time quartiles. However, using the same numerical cutoffs, this was not the case. The difference relates to changes to a more strict definition for hypertension over time.


http://hemodialysis.com/demographic-metabolic-and-blood-pressure-characteristics-of-living-kidney-donors-spanning-five-decades/










Demographic, metabolic, and blood pressure characteristics of living kidney donors spanning five decades.Hemodialysis.com Author Interview with Sandra J. Taler, M.D. Consultant, Division of Nephrology/Hypertension

Associate Professor of Medicine | College of Medicine |Mayo Clinic | 200 First Street SW | Rochester, MN 55905(cont)

• Hemodialysis.com: What should clinicians and patients take away from this study?

• Dr. Taler: As the entire United States population is aging and becoming more obese, accepted kidney donors also reflect these trends.

• Hemodialysis.com: What recommendations do you have for future research as a result of your study?

Dr. Taler: We are looking at outcomes for the donors in this study. It is important that living kidney donors have access to medical care so they can be evaluated and treated for hypertension, diabetes or other metabolic abnormalities should they develop.

• Citation:• Demographic, metabolic, and blood pressure characteristics of living kidney donors spanning five

decades.• Taler SJ, Messersmith EE, Leichtman AB, Gillespie BW, Kew CE, Stegall MD, Merion RM, Matas AJ,

Ibrahim HN; RELIVE Study Group.• Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA• Am J Transplant. 2013 Feb;13(2):390-8. doi: 10.1111/j.1600-6143.2012.04321.x. Epub 2012 Nov 8.









Single Pediatric Kidney Transplantation in Adult Recipients: Comparable Outcomes With Standard-Criteria Deceased Donor Kidney TransplantationHemodialysis.com Interview with: Dr

Amit Sharma MD. MPhilAssistant Professor Director, Transplant Surgery Fellowship ProgramHume-Lee Transplant CenterVirginia Commonwealth University Richmond, Virginia, USA

• Hemodialysis.com: What are the main findings of the study?• Dr. Sharma: Single pediatric kidney transplantation (SKT) in to adult recipients has traditionally been considered high risk

due to concerns of technical complications leading to poor graft outcomes. As a result many transplant centers hesitate to utilize these kidneys for transplantation. We retrospectively compared outcomes in adult recipients after SKT (n=31), standard criteria deceased donor kidney transplantation (SCDKT, n=283), pediatric en bloc, (EBKT, n=21), living donor (LDKT, n=275) and extended criteria donor, (ECD, n=100) kidney transplantation.

• The mean donor age and weight for pediatric single kidney donors were 6.3 years and 27.6 kg. The recipients selected for SKT weighed significantly less (67.6 ± 21.4 kg), p<0.0001) compared to the SCDKT recipients. There were no re-transplant candidates in SKT group while 14.5% of SCDKT recipients had previous kidney transplants. The superior quality of single pediatric kidneys was reflected by the serum creatinine which at 1-year was significantly lower than ECD, and by 5-years was lower than both SCDKT and ECD (p<0.0001). Compared to standard criteria donors (SCDKT), the single pediatric kidney transplant (SKT) group had a higher incidence of renal arterial anastomotic stenosis (6.8% vs. 0.4%, p=0.02), hydronephrosis (12.9% vs. 5.3%, p=0.02) and a higher incidence of acute rejection (9.7% vs. 6.0%, p=0.03). Subgroup analysis of the SKT cohort by donor age below 5 vs. 6-10 years (mean weight 16.4 kg vs. 32.7 kg) revealed that there were no differences in serum creatinine, patient survival or death-censured graft survival.

• Hemodialysis.com: Were any of the findings unexpected?• Dr. Sharma: We did not see any significant difference in the incidence of delayed graft function between SKT (45.2%) and

SCDKT (50.5%) groups. This indicates good donor-recipient weight matching that may have prevented problems due to low nephron mass. Patient survival at 1- and 5-years after single pediatric kidney transplants (SKT) was lower than SCDKT at both time points (p=0.02). Despite the higher rate of vascular and urological complications, the 5- year death-censored graft survival after SKT (81.4 ± 7.6%) was significantly superior to both SCDKT (74.5 ± 3.4%) and ECD (74.6 ± 5.8%, p=0.02).


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Single Pediatric Kidney Transplantation in Adult Recipients: Comparable Outcomes With Standard-Criteria Deceased Donor Kidney TransplantationHemodialysis.com Interview with: Dr

Amit Sharma MD. MPhilAssistant Professor Director, Transplant Surgery Fellowship ProgramHume-Lee Transplant CenterVirginia Commonwealth University Richmond, Virginia, USA(cont)


Dr. Sharma: With careful donor and recipient selection, single pediatric kidney transplantation in to adult recipients offers superior long-term graft outcomes compared to standard criteria deceased donor kidney transplantation. Kidneys from pediatric donors who weigh more than 15 kg or with kidney size greater than 6 cm should be split and transplanted singly in order to optimize resource utilization. Recipients with certain high-risk criteria should be avoided to ensure successful graft outcomes after SKT. Post-transplant management of SKT recipients should include strict control of hypertension, aspirin for at least one year and vigilant immunosuppression monitoring to prevent rejections. In our experience, complications like arterial stenosis and hydronephrosis can be successfully managed by experienced interventional radiologists. Use of pediatric donor kidneys needs to be continuously encouraged to address the problem of organ shortage.


• Dr. Sharma: We have proposed a few strategies to optimize both the utilization and outcomes after transplantation of single pediatric kidneys in to adult recipients. These include the need for policies to expedite pediatric kidney placement in order to minimize cold ischemia times. Facilitating organ procurement and transplantation by experienced operators could reduce the technical complications. Future research should also focus on newer immunosuppressive strategies to lower rejection rates and further improve pediatric kidney allograft survival.

• Citation:• Single Pediatric Kidney Transplantation in Adult Recipients: Comparable Outcomes With Standard-Criteria Deceased-Donor Kidney

Transplantation• Sharma, Amit; Ramanathan, Rajesh; Behnke, Martha;

Fisher, Robert; Posner, Marc• Transplantation:• POST AUTHOR CORRECTIONS, 15 March 2013 doi: 10.1097/TP.0b013e31828a9493

















Modifiable Patient Characteristics and Racial Disparities in Evaluation Completion and Living Donor TransplantHemodialysis.com Interview with: Dr. Amy D. WatermanGeneral Medical Sciences, Washington University School of Medicine

Campus Box 8005, 660 S. Euclid Avenue, St. Louis, MO 6311

• Hemodialysis.com: What are the main findings of the study?• Dr. Waterman:• In an analysis of 695 Black and White patients in kidney failure who presented for

transplant and were followed over 6 years, Black patients initially presented for evaluation having received less transplant education, being less knowledgeable about transplantation, and less willing to pursue deceased or living donor transplantation than Whites.

• Patients who began their transplant evaluation process with a greater knowledge of transplantation and greater motivation to receive living donor transplants were ultimately more successful at receiving a living donor transplant six year later.

• Hemodialysis.com: Were any of the findings unexpected?• Dr. Waterman:• Though we knew that modifiable patient characteristics, like how much knowledge or

education of transplant a patient has, were important in understanding whether patients will pursue or get a transplant, we were surprised to see that, in our analysis, these were some of the most important predictors of whether patients would pursue or get a transplant.


http://hemodialysis.com/modifiable-patient-characteristics-and-racial-disparities-in-evaluation-completion-and-living-donor-transplant/






Modifiable Patient Characteristics and Racial Disparities in Evaluation Completion and Living Donor TransplantHemodialysis.com Interview with: Dr. Amy D. WatermanGeneral Medical Sciences, Washington University School of Medicine

Campus Box 8005, 660 S. Euclid Avenue, St. Louis, MO 6311(cont)

• Hemodialysis.com: What should clinicians and patients take away from this study?• Dr. Waterman:• These findings suggest that improved education, especially for patients of color, may help more patients

successfully get transplants. Educational interventions focused on helping improve patients’ transplant knowledge and motivation when patients’ kidneys are starting to fail or afterwards may reduce or overcome racial disparities in transplantation. Education in dialysis centers about transplant could be incredibly beneficial to patients’ transplant success years later.

• Hemodialysis.com: What recommendations do you have for future research as a result of your study?• Dr. Waterman:• Future research should compare the potential for different educational interventions in dialysis centers and

community nephrologists’ offices to help patients, especially patients of color, obtain more knowledge of transplant and become more willing to get a transplant. Research should also look at the best ways to deliver these interventions so that they can help all patients move toward transplant more quickly, easily, and cost-effectively.

• Citation:• Modifiable Patient Characteristics and Racial Disparities in Evaluation Completion and Living Donor

Transplant• Amy D. Waterman, John D. Peipert, Shelley S. Hyland, Melanie S. McCabe,

Emily A. Schenk, and Jingxia Liu• CJASN CJN.08880812; published ahead of print March 21, 2013, doi:10.2215/CJN.08880812







Estimated GFR reporting is associated with decreased NSAID drug prescribing and increased renal functionHemodialysis.com Author Interview: Dr Li WeiSenior Lecturer Department of Practice and PolicyUCL School of Pharmacy Tavistock

Square London WC1H 9JP


• Dr. Li: The study was a population-based longitudinal analysis using a record-linkage database in Tayside, Scotland, UK. The aim of the study was to determine NSAID prescribing before and after the implementation of estimated eGFR reporting and to evaluate renal function in patients who used NSAIDs but stopped these after the first eGFR report. The study found that prescriptions for NSAIDs significantly decreased after the implementation of eGFR reporting. eGFR reporting was associated with reduced NSAID prescriptions (adjusted OR, 0.78 95%CI 0.75-0.82). NSAID prescribing rates in the 6 months prior to April 2006 were 18.8%, 15.4% and 7.0% in patients with CKD stages 3, 4, and 5 and 15.5%, 10.7% and 6.3% respectively, after eGFR reporting commenced. In patients who stopped NSAID treatment, eGFR significantly increased from 45.9 to 46.9, 23.9 to 27.1, and 12.4 to 26.4 ml/min per 1.73m2 in 1340 stage 3 patients, 162 stage 4 patients, and 9 stage 5 patients, respectively.


• Dr. Li: no• Hemodialysis.com: What should clinicians and patients take away from this study?

• Dr. Li: GFR reporting may result in safer prescribing. The study shows the enormous benefit to the NHS of the processing of routinely captured data. Careful monitoring of eGFR in patients taking NSAIDs is the key component of safe clinical practice.


• Dr. Li: The study was confined to a single NHS region, and a further study on different populations and a further questionnaire survey of physician behavior would strengthen the study finding.

• Citation:• Estimated GFR reporting is associated with decreased nonsteroidal anti-inflammatory drug prescribing and increased renal function• Wei L, Macdonald TM, Jennings C, Sheng X, Flynn RW, Murphy MJ.• of Practice and Policy, UCL School of Pharmacy, London, UK [2] Medicines Monitoring Unit, Division of Medical Sciences, University of Dundee,

Ninewells Hospital and Medical School, Dundee, Scotland, UK.Kidney Int. 2013 Mar 13. doi: 10.1038/ki.2013.76. [Epub ahead of print]


http://hemodialysis.com/estimated-gfr-reporting-is-associated-with-decreased-nsaid-drug-prescribing-and-increased-renal-function/










Effect of serum FGF-23, MGP and fetuin-A on calcium-phosphate metabolism in maintenance hemodialysis patientsHemodialysis.com Interview with Jian-Ying NiuDivision of Nephrologythe Fifth People’s Hospital of Shanghai 200240 China

• Hemodialysis.com: What are the main findings of the study?• Answer: In this study, we enrolled 64 patients (30 males,34 females, 60.6+-

11.3 years of age) who received an average dialysis vintage of 6.88+-2.94 years, and evaluated the serum level of FGF-23, MGP and fetuin-A, as well as the coronary artery calcification score (CACS) with coronary artery computed tomography scan.

• There were 13 (20.31%), 16 (25%), and 35 (54.69%) patients exhibited a CACS of 0–100, 100–400, and >400, respectively. The dialysis vintage, serum FGF-23, fetuin-A, phosphorus and high-density lipoprotein-C levels were identified as independent variables of CACS by stepwise multiple regression analysis. The area under receiver operating characteristic curve indicated that serum FGF-23 and fetuin-A were useful for identifying CAC in MHD patients. The cut-off value corresponding to the highest Youden’s index was serum FGF-23 ≥ 256 pg/mL and fetuin-A ≤ 85mg/mL, which was defined as the optimal predictors of CAC.


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Effect of serum FGF-23, MGP and fetuin-A on calcium-phosphate metabolism in maintenance hemodialysis patientsHemodialysis.com Interview with Jian-Ying NiuDivision of Nephrologythe Fifth People’s Hospital of Shanghai 200240 China(cont)

• Hemodialysis.com: Were any of the findings unexpected?• Answer: Our study did not find that MGP was closely related to CAC in MHD patients. This may

be due to small sample size, measurement of overall serum MGP without differentiation between ucMGP and active MGP, and unknown vitamin K status in MHD patients.

• It is reported in literature[1] that increased serum uncarboxylated MGP (ucMGP) is associated with the severity of aorta calcification.

• ucMGP can be used as a surrogate marker of vascular calcification in CKD patients. The ucMGP level is inversely correlated with CAC. A study in 53 MHD patients[2] documented that the baseline ucMGP level in MHD patients was 4.5 times higher than that in normal subjects. This confirms that vitamin K deficiency is prevalent in MHD patients. Daily supplementation of exogenous vitamin K can reduce ucMGP level, which provides support for improving vascular calcification in MHD patients.

• [1]Schurgers LJ, Barreto DV, Barreto FC, et al. The circulating inactive form of matrix gla protein is a surrogate marker for vascular calcification in chronic kidney disease: a preliminary report.Clin J Am Soc Nephrol..2010; 5:568–575.

• [2]Westenfeld R, Schafer C, Smeets R, et al. Fetuin-A(AHSG) prevents extraosseous calci fication induced by uraemia and phosphate challenge in mice.Nephrol Dial Transplant. 2007; 22:1537–1546.







Effect of serum FGF-23, MGP and fetuin-A on calcium-phosphate metabolism in maintenance hemodialysis patientsHemodialysis.com Interview with Jian-Ying NiuDivision of Nephrologythe Fifth People’s Hospital of Shanghai 200240 China(cont)

• Hemodialysis.com: What should clinicians and patients take away from this study?• Answer: CAC is prevalent in MHD patients. In this study, stepwise multiple regression analysis found that

serum FGF-23 and fetuin-A levels are closely associated with the severity of CAC in MHD patients. ROC curve also confirmed that both serum FGF-23 and Fetuin-A are biomarkers for identifying CAC in MHD patient with good sensitivity and specificity. These two markers are useful for clinical prediction of CAC, especially in combination or in series.They are expected to be used as promising diagnostic markers for predicting CAC in MHD patients.

• Hemodialysis.com: What recommendations do you have for future research as a result of your study?• Answer: As mentioned before, our study did not find that MGP was closely related to CAC in MHD patients.

This may be due to small sample size, measurement of overall serum MGP without differentiation between ucMGP and active MGP, and unknown vitamin K status in MHD patients. Therefore, further study is required to clarify the exact role of MGP in CAC in MHD patients.

• Citation:• Effect of serum FGF-23, MGP and fetuin-A on calcium-phosphate metabolism in maintenance hemodialysis

patients• Xiao DM, Wu Q, Fan WF, Ye XW, Niu JY, Gu Y.• Division of Nephrology, the Fifth People’s Hospital of Shanghai, Fudan University, Shanghai, China; Division

of Internal Medicine,Ningbo First Hospital, Medical School of Ningbo University, Ningbo, China.Hemodial Int. 2013 Mar 12. doi: 10.1111/hdi.12033. [Epub ahead of print]







High incidence of mild hypernatremia in females using ecstasy at a rave partyHemodialysis.com Interview with Geetruida D. van Dijken

Department of Nephrology and Hypertension, University Medical Centre Utrecht, Utrecht, the Netherlands


• Answer: We decided to study the incidence of hypernatremia in subjects using 3, 4–methylenedioxymethamphetamine (MDMA) at an indoor rave party. Only 3% of males, but no less than ~25% of females attending a rave party and using MDMA developed mild hypernatremia during the event. Especially females are therefore probably also at risk of developing severe symptomatic hypernatremia. Not using MDMA is obviously the best option to prevent MDMA–induced hypernatremia. However, accepting the fact that millions use the drug every weekend, strategies should also be developed to prevent hypernatremia in subjects choosing to take MDMA. This would include matching the electrolyte content of the fluids and food ingested to that of the fluids that are lost during the use of MDMA, mainly by perspiration. Users of MDMA and emergency health care workers should become more aware of the relatively high incidence of MDMA–induced hypernatremia and of potential strategies to prevent this complication.


http://hemodialysis.com/high-incidence-of-mild-hyponatraemia-in-females-using-ecstasy-at-a-rave-party/








Department of Nephrology and Hypertension, University Medical Centre Utrecht, Utrecht, the Netherlands(cont)

• Hemodialysis.com: Were any of the findings unexpected?• Answer: An intriguing observation is that the mean plasma sodium concentration in

females not using MDMA at the rave party was significantly lower than in males not taking the drug, although there were no frank cases of hypernatremia in these females. Due to the design of the study, the plasma sodium concentrations at entry are not known, and it cannot be excluded that the initial values in females were already lower than in males.

• Although the plasma sodium concentration appears to be slightly lower in females in the luteal phase compared with males, there is no gender specific normal range for the plasma sodium concentration in females not stratified for the phase of the luteal cycle and males. Consequently, it is possible that exercise and stress-induced ADH secretion combined with intake of hypotonic fluids caused the reduction in plasma sodium concentration in female ravers not using MDMA. In this respect, the situation may be similar to the hypernatremia induced by long distance running, which also occurs more frequently in females than males and may have a similar pathophysiology.









Department of Nephrology and Hypertension, University Medical Centre Utrecht, Utrecht, the Netherlands(cont)

• Hemodialysis.com: What should clinicians and patients take away from this study?• Answer: When you see a patient in your hospital that feels unwell after using ecstasy / MDMA

please remember that hyponatremia could be a cause.

• Even a low dose of ecstasy can cause hyponatremia and after a short time of ingestion. Especially in women we found a high percentage of hyponatremia. Advising users to drink a lot of fluids seems unwise. Normal saline should not be administered readily by healthcare workers. If necessary for resuscitation hypertonic fluids can be considered.


• Answer: We would like to research preventative measurements, for instance drinking soup when using MDMA.

• Citation: • High incidence of mild hypernatremia in females using ecstasy at a rave party• Geetruida D. van Dijken, Renske E. Blom, Ronald J. Hené,

and Walther H. Boer• Nephrol. Dial. Transplant. first published online March 8, 2013 doi:10.1093/ndt/gft023








Association Between Aristolochic Acid and CKD: A Cross-sectional Survey in China.Hemodialysis.com Interview with Authors Wenke Wang and Jian ZhangHospital Authority Toxicology Reference Laboratory

Princess Margaret Hospital, Hong Kong SAR, China

• Hemodialysis.com: What are the main findings of the study?• Response: Altogether, 467 participants reported long-term AA intake, with an adjusted

prevalence of 1.5% (95% CI, 1.2%-1.7%).• After adjusting for age and sex, long-term AA intake was associated with eGFR < 60 mL/min/1.73

m2 and albuminuria, with ORs of 2.20 (95% CI, 1.51-3.12) and 1.67 (95% CI, 1.27-2.20), respectively.

• Adjusting for other covariates attenuated the ORs, which were 1.83 (95% CI, 1.22-2.74) and 1.39 (95% CI, 1.03-1.87) for eGFR < 60 mL/min/1.73m2 and albuminuria, respectively.

• A positive association between accumulated time of AA intake and kidney damage also was observed, with fully adjusted ORs of 1.07 (95% CI, 1.03-1.12) per 6-month longer intake for eGFR < 60 mL/min/1.73 m2 and 1.04 (95% CI, 1.01-1.08) per 6-month longer intake for albuminuria.


• Response: AA has been shown to be associated with urothelial cancer in many studies, which might be related to the formation of AA-DNA adducts. Hematuria is one of the major clinical manifestations of urothelial cancer. However, we did not observe an association between long-term AA intake and hematuria in our study.


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Association Between Aristolochic Acid and CKD: A Cross-sectional Survey in China.Hemodialysis.com Interview with Authors Wenke Wang and Jian ZhangHospital Authority Toxicology Reference Laboratory

Princess Margaret Hospital, Hong Kong SAR, China(cont)

• Hemodialysis.com: What should clinicians and patients take away from your report?

• Response: Our nationwide study showed long-term intake of medications containing AA is prevalent in China and is associated with the presence of CKD.

• Strategies to eliminate those medications from the market should be strengthened, which could constitute a cost-effective way to cope with the challenge of CKD in China.

• Hemodialysis.com: What recommendations do you have for future research as a result of this study?

• First, if use of medications containing AA information can be reported from prescriptions would be more reliable.• Second, we would get more information about more and more herbs containing AA, and try our best to estimate the

mean dose of AA, so that the dose-related effects may be assessed.• Third, we would get more information on markers of tubular injury.• Finally, the cross-sectional design of the study makes inference of a causal relationship between CKD and AA

impossible. Maybe we can carry out a cohort study or A case-control study to reveal the causal relationship between CKD and AA.

• Citation:• Association Between Aristolochic Acid and CKD: A Cross-sectional Survey in China.• Zhang J, Zhang L, Wang W, Wang H; China National Survey of Chronic Kidney Disease Working Group.• Division of Nephrology, Chifeng Second Hospital; Chifeng, China.

Am J Kidney Dis. 2013 Mar 2. pii: S0272-6386(13)00032-2. doi: 10.1053/j.ajkd.2012.12.027.[Epub ahead of print]







Stress and Burnout Among Nephrology Dialysis StaffHemodialysis.com Author Interview: Macaulay Onuigbo MD MSc FWACP FASN MBA

Associate Professor of Medicine, College of Medicine, Mayo Clinic, Rochester, MN.Nephrologist, Mayo Clinic Health System, Eau Claire, WIVice Chairman, Nephrology department, MCHSEC. MBA Executive.(cont)

• Hemodialysis.com: Why was the study carried out in the first place?• Dr. Onuigbo: The concept of burnout in the workplace was introduced in the late 1970s,

mainly in a US context. Healthcare delivery is generally acknowledged to be a stressful industry but few studies in this area are available. Even far less reported is stress or burnout in nephrology and/or dialysis practices.

• The potential impact of the recent increasing role of the EMR in the healthcare workplace was also investigated here especially with reference to the effects of an EMR on provider perceptions of work stress and burnout. This was even more pertinent following our recent report in the Wisconsin Medical Journal of the new unrecognized syndrome of “Physician Cognitive Drift” as it relates to some unintended consequences of the EMR and as a major source of physician stress in the healthcare workplace.

• Hemodialysis.com: What is the Methodology of the study?• Dr. Onuigbo: This was a cross-sectional hand delivered questionnaire-based survey of

physicians, nurses, dialysis technicians, social workers and dieticians in a nephrology-dialysis practice in a Northwestern Wisconsin Mayo Clinic Dialysis Unit. The questionnaire used for this survey is the Oldenburg Burnout Inventory (OLBI) and the survey was carried out in January 2012.


http://hemodialysis.com/stress-and-burnout-among-nephrology-dialysis-staff/










• Hemodialysis.com: What are the main findings of the study?• Dr. Onuigbo: Eighteen survey questionnaires were distributed across the clinic and 16 (89%)

were returned in a completed form, giving a response rate of 89%. The participating staff was mostly female nurses, age range 30-60, average age about 40 years.

• The average emotional exhaustion score on the OLBI was 2.66, consistent with a low level of emotional exhaustion. The average disengagement score was 2.45, consistent with a low level of disengagement.

• One recurring source of stressors for the staff revolved around the non user-friendliness of the EMR system(s) – the so-called EMR-induced stresses – including too much time spent on data entry, the simultaneous use of multiple and non-interlined EMR systems, slow EMR systems and so on.

• Hemodialysis.com: Were any of the findings unexpected?• Dr. Onuigbo: We were surprised at the low level of stress and burnout, in general, evident

from this dialysis staff survey. The low level of emotional exhaustion and disengagement reported amongst was pleasantly surprising. Higher levels had been anticipated, especially with the inclusion of the dialysis nurses who have often expressed higher levels of anxiety about work-related stressors.










• Hemodialysis.com: What should clinicians and patients take away from your report?• Dr. Onuigbo: The urgent need for solutions to healthcare related stress and burnout

calls for more studies. Stress and burnout among healthcare personnel is an understudied phenomenon and demands more studies. Staff stress and burnout could lead to reduced staff retention, medical and other errors and overall poor employee productivity. Furthermore, the mixture of both clerical staff and clinical staff may have diluted down the average stress and burnout scores obtained from this dialysis staff survey. Moreover, the near absent participation of physicians may have also affected the study results,

• The addition of the EMR has often led to an escalation of staff stress and burnout and requires close monitoring. Some solutions offered by participating staff to ease EMR-induced stress included the following:

• v More robust, user-friendly, fast, agile, nimble and flexible EMR (No Cognitive Drift).• v Reduced redundancy of multiple EMRs requiring multiple data entry procedures.• v The involvement of providers early in the IT design, implementation and ongoing

review of the EMR.








Stress and Burnout Among Nephrology Dialysis StaffHemodialysis.com Author Interview: Macaulay Onuigbo MD MSc FWACP FASN MBAAssociate Professor of Medicine, College of Medicine, Mayo Clinic, Rochester, MN.

Nephrologist, Mayo Clinic Health System, Eau Claire, WIVice Chairman, Nephrology department, MCHSEC.MBA Executive.


• Dr. Onuigbo: Larger studies, focused on specific healthcare professionals with significant emphasis on stressful work-arounds for nurses, EMR-induced stress for physicians and other providers, and better EMR training to reduce staff stress and burnout would be necessary.












Associate Professor of Medicine, College of Medicine, Mayo Clinic, Rochester, MN.Nephrologist, Mayo Clinic Health System, Eau Claire, WIVice Chairman, Nephrology department, MCHSEC.MBA Executive.

• REFERENCES• Onuigbo MA. Physician ‘cognitive drift’ and medication errors–

unintended consequences of the modern EMR. WMJ. 2012 Oct;111(5):198.

• Halbesleben JRB, Wakefield DS, Wakefield BJ. Work-arounds in health care settings: Literature review and research agenda. Health Care Management Review: January/March 2008 – Volume 33 – Issue 1 – pp 2-12

• Dahlin M, Runeson B, Jönsson M, Öjehagen A. Stress in medical students at KI and Lund University. What do we have in common and what is different? http://ki.se/ki/jsp/polopoly.jsp?d=1274&a=2274&cid=1289&l=en.








http://ki.se/ki/jsp/polopoly.jsp?d=1274&a=2274&cid=1289&l=en


Experience of HeRO Dialysis Graft Placement in a Challenging PopulationHemodialysis.com Interview with: Harry Schanzer, M.D., F.A.C.S.Clinical Professor of SurgeryDivision of Vascular SurgeryMount Sinai School of Medicine

• Hemodialysis.com: What are the main findings of the study?• Dr. Schanzer: Eleven patients with central venous occlusive disease underwent 12

HeRO placements as a last ditch effort for long-term hemodialysis access. At one year, primary and secondary patencies were 9.1% and 45.5%. Four HeRO grafts were never cannulated, and the remaining 11 had a functional patency of an average of 14 months

• Hemodialysis.com: Were any of the findings unexpected?• Dr. Schanzer: These findings were surprising for us, since recent published studies

demonstrated a secondary patency at 24 months as high as 86.7%.1 It is possible that our subset of patients had more severe central venous occlusive disease than in the other studies, although it is difficult to compare since detailed descriptions of the patient population in the studies with higher patency were not included. Our inferior results may also be due to the small sample size and less than aggressive approach to maintaining secondary patency with declotting procedures.


http://hemodialysis.com/experience-of-hero-dialysis-graft-placement-in-a-challenging-population/










Experience of HeRO Dialysis Graft Placement in a Challenging PopulationHemodialysis.com Interview with: Harry Schanzer, M.D., F.A.C.S.Clinical Professor of SurgeryDivision of Vascular Surgery

Mount Sinai School of Medicine(cont)

• Hemodialysis.com: What should clinicians and patients take away from this study?• Dr. Schanzer: The group of patients who require the HeRO graft for dialysis is especially

challenging. In order for the HeRO to be a consideration, all other upper extremity hemodialysis accesses excluding catheters, must have been exhausted.2 Furthermore, each of these patients is unique, and we believe that the range in patency rates is likely due to the variety of anatomic hurdles that must be overcome. The most important concept to be taken away from this study is that even if the HeRO only remains functional for 1 year, that is one year without a catheter. Studies have reported tunneled dialysis catheter rates of infection-associated mortality up to 34%,3 thus fewer days with a catheter may reduce morbidity and mortality. Finally, in order to maintain secondary patency in these devices, close follow-up and aggressive declotting is necessary.


• Dr. Schanzer: Prospective studies with larger samples of patients need to be conducted. It is imperative that the patients be stratified according to their anatomic difficulty of creating a successful permanent hemodialysis access. Consequently, determining which patients will benefit the most from the HeRO may contribute to improved patency rates and longer functionality.








Experience of HeRO Dialysis Graft Placement in a Challenging PopulationHemodialysis.com Interview with: Harry Schanzer, M.D., F.A.C.S.Clinical Professor of SurgeryDivision of Vascular Surgery

Mount Sinai School of Medicine(cont)

• Citation:• Experience of HeRO Dialysis Graft Placement in a Challenging Population.• Kokkosis AA, Abramowitz SD, Schwitzer J, Schanzer H, Teodorescu VJ.

Vasc Endovascular Surg. 2013 Mar 10. [Epub ahead of print]• References:• 1. Gage SM, Katzman HE, Ross JR, Hohmann SE, Sharpe CA, Butterly DW, Lawson JH.

Multi-center experience of 164 consecutive Hemodialysis Reliable Outflow [HeRO] graft implants for hemodialysis treatment. Eur J Vasc Endovasc Surg. 2012 Jul;44(1):93-9

• 2. Steerman SN, Wagner J, Higgins JA, Kim C, Mirza A, Pavela J, Panneton JM, Glickman MH. Outcomes comparison of HeRO and lower extremity arteriovenous grafts in patients with long-standing renal failure. J Vasc Surg. 2013 Mar;57(3):776-83. doi: 10.1016/j.jvs.2012.09.040. Epub 2013 Jan 11.

• 3. Danese M, Griffiths R, Dylan M, Yu H, Dubois R, Nissenson A. Mortality differences among organisms causing septicemia in haemodialysis patients. Hemodial Int, 10 (2006), pp. 56–62








he Associations between Race and Geographic Area and Quality-of-Care Indicators in Patients Approaching ESRDHemodialysis.com: Interview withGuofen Yan, Ph.D.Associate Professor

Department of Public Health Sciences, School of MedicineUniversity of Virginia Charlottesville, Virginia 22908-07

• Hemodialysis.com: What are the main findings of the study?• Dr. Yan: A body of evidence has established that timely receipt of care from a kidney specialist over the

course of chronic kidney disease (CKD) is important for receiving optimal kidney care, including slowing the disease, improving survival while on long-term dialysis, and increasing the likelihood of receiving a kidney transplant. While clinical guidelines recommend that all patients in later stages of CKD be under the care of kidney specialists, 25% to 50% of patients on dialysis in the United States had not received such care before they developed kidney failure, or end-stage renal disease (ESRD).

• We undertook a national study to examine whether geography plays any role in access to pre–ESRD care among black and white CKD patients. We analyzed information from 404,622 white and black adult patients receiving dialysis between 2005 and 2010 and residing in 3,076 counties across the United States. The counties were grouped into large metropolitan, medium/small metropolitan, suburban, and rural counties.

• We found that pre-ESRD care measures are highly variable among geographic areas defined by urban/rural characteristics. Fewer patients received nephrologist care for more than 12 months before developing ESRD in large-metro (25.7%) and rural (26.9%) counties than in medium/small-metro counties (31.6%). In all four geographic areas, black patients received less pre-ESRD care than their white counterparts. In large-metro counties, black patients were 27% less likely than whites to receive nephrologist care for more than 12 months before developing ESRD. In rural counties, they were 16% less likely. In suburban and rural counties, black patients were 30% to 52% less likely than whites to see a dietitian before developing ESRD.


http://hemodialysis.com/the-associations-between-race-and-geographic-area-and-quality-of-care-indicators-in-patients-approaching-esrd/%23more-531









he Associations between Race and Geographic Area and Quality-of-Care Indicators in Patients Approaching ESRDHemodialysis.com: Interview withGuofen Yan, Ph.D. Associate Professor

Department of Public Health Sciences, School of MedicineUniversity of Virginia Charlottesville, Virginia 22908-07(cont)

• Hemodialysis.com: Were any of the findings unexpected?• Dr. Yan: We found that for all the pre-ESRD care measures examined, the difference across the four

types of geographic areas was much greater for black patients than white patients. For example, in large-metro counties, the proportions of receiving dietitian care for white and black patients were both about 19%; however, in rural counties, only 8% of rural black patients (more than a 50% reduction from 19% in large-metro) received such care, compared with 16.8% of rural white patients. Consequently, in certain geographic areas black patients were substantially less likely to have received kidney specialist care than white patients, such as very limited access to dietitian care for black patients living in rural counties.

• Hemodialysis.com: What should clinicians and patients take away from this study?• Dr. Yan: A Healthy People 2020 objective is to increase the proportion of CKD patients who receive

nephrologist care at least 12 months before the start of renal replacement therapy. Our study shows that currently the proportion ranges from 21% to 33%, depending on the geographic location and race. Possible explanations for the lower proportions include differences in referral patterns between healthcare providers in different geographic areas, noncompliance of patients to the referral, limited access to kidney specialists in some geographic areas, or financial constraints for patients with low socioeconomic status. We need national concerted efforts, from health care providers, policy makers, and patients, to identify and remove the barriers to access to kidney specialists.














• Dr. Yan: The significant geographic differences in receiving pre-kidney failure care and the substantially large racial differences in certain geographic areas highlight the complexity of the issue. Many health care policies are driven by the degree of urbanization of a given county, but the recommendations are often based on limited data. Our findings suggest improving receipt of key pre-ESRD indicators will require more refined regional characterization of health care needs and resources, working with kidney organizations around employment opportunities for new graduates. Healthcare polices directed at eliminating pre-ESRD care disparities must take these complexities and granular data into consideration. Future studies to delineate the factors that are responsible for urban-rural differences as well as variations within counties may allow for more strategic and public health oriented approaches to improve care for all Americans with CKD.











• Citation:• The Associations between Race and Geographic Area and Quality-of-

Care Indicators in Patients Approaching ESRD• Yan G, Cheung AK, Ma JZ, Yu AJ, Greene T, Oliver MN, Yu W, Norris KC.• Department of Public Health Sciences and , ‖Department of Family

Medicine, University of Virginia School of Medicine, Charlottesville, Virginia;, †Division of Nephrology & Hypertension and, §Division of Epidemiology, University of Utah, Salt Lake City, Utah;, ‡Dornsife College of Letters, Arts, and Sciences and Keck School of Medicine, University of Southern California, Los Angeles, California, ¶Charles R. Drew University of Medicine and Science, Los Angeles, California.Clin J Am Soc Nephrol. 2013 Mar 14. [Epub ahead of print]









The CKD Enigma – Statistics and Myths about CKD: Conflicting ESRD and Death Rates in the LiteratureHemodialysis.com Interview with Macaulay Onuigbo MD MSc FWACP FASN MBAAssociate Professor of Medicine, College of Medicine, Mayo Clinic, Rochester, MN.

Nephrologist, Mayo Clinic Health System, Eau Claire, WIVice Chairman, Nephrology department, MCHSEC.MBA Executive

• Hemodialysis.com: Why was the study carried out in the first place?• Dr. Onuigbo: Over the years, the CKD literature had demonstrated a huge disparity in the

reported annual death rates and annual ESRD rates among different CKD cohorts both here in the USA and around the world. There is this unproven yet commonly accepted consensus that “most CKD patients die (of CV events) before they reach ESRD”. Yet there are reports out there in the nephrology literature showing much higher ESRD rates than death rates in CKD cohort studies. Keith et al (2004) reported an ESRD Rate of 20% and a higher Death Rate of 50% after 5 years, among a CKD cohort of 27,998 patients in a managed care organization. Quite the opposite, Menon et al (2008) demonstrated a higher ESRD Rate of 60% and a Death Rate of 15% after 88 months in 1,666 patients in the Modification of Diet in Renal Disease (MDRD) study. Onuigbo & Onuigbo (2009), in a single-center Mayo Clinic study revealed an ESRD Rate of 18% and a Death Rate of 13% after 4 years among a 100-patient high risk CKD cohort in an angiotensin inhibition withdrawal study.

• We therefore set out to compare projected annual ESRD incidence among the general US CKD population based on current literature versus actual US ESRD incidence as reported in the United States Renal Data System (USRDS) for the year ending December 2008.


http://hemodialysis.com/the-ckd-enigma-statistics-and-myths-about-ckd-conflicting-esrd-and-death-rates-in-the-literature/%23more-520











Nephrologist, Mayo Clinic Health System, Eau Claire, WIVice Chairman, Nephrology department, MCHSEC.MBA Executive(cont)

• Hemodialysis.com: What was the Methodology of the study?• Dr. Onuigbo: In mid-2012, we carried out a snap shot cross-sectional US 2007 CKD

population-wide analysis of projected annualized ESRD incidence based on the weighted rates from the three cited sources. We then compared these estimates with actual US ESRD incidence as reported in USRDS 2010 report for 2008.

• A 2007 US CDC report indicated that 16.5% of the U.S. population 20 years of age and older had CKD with eGFR <60 ml/min/1.73 sq m BSA, thus affecting >20 million adult Americans.

• The above 3 cited studies combined, give a weighted average annualized ESRD Rate of ~4.2% among the US CKD population.

• Hemodialysis.com: What are the main findings of the study?• Dr. Onuigbo: Projections for new ESRD resulted in an estimated 840,000 new ESRD cases

in 2008.• According to the 2010 USRDS Annual Data Report, the actual reported new ESRD

incidence in 2008 was in fact only 112,476 (FIGURE). This represented a gross overestimation by about 650% of the ESRD incidence in the US for the year ending 2008 – clearly a colossal failure of epidemiological analysis.










• Hemodialysis.com: Were any of the findings unexpected?• Dr. Onuigbo: The magnitude of the disparity between estimated ESRD

rates and the actual ESRD incidence for 2008 was mind-boggling. Similar results would be obtained for annual death rates comparisons. Thus, the natural history of CKD remains unclear and the nephrology literature is rife with very dissimilar and conflicting data regarding ESRD Rates and Death Rates among different reported CKD cohorts.

• Moreover, these results simply confirm the conclusions of the recently released (August 2012) US Preventive Services Task Force (USPSTF) Report on CKD screening which concluded that we know surprisingly little about whether screening adults with no signs or symptoms of CKD will improve health outcomes and that clinicians and patients deserve better information on CKD.










• Hemodialysis.com: What should clinicians and patients take away from your report?• Dr. Onuigbo: That we as physicians in general, and nephrologists in particular, still do not understand the true natural

history of CKD, its prognostication, ESRD prediction, and the true ESRD Rates and Death Rates among CKD cohorts.• The clear heterogeneity of the so-called “CKD patient” is brought into prominence as we review the very misleading

concept of classifying and prognosticating all CKD patients as if CKD represented one homogenous patient population.• Current consensus that ‘most CKD patients all die of cardiovascular events before reaching ESRD’ is simply a myth, is

unfounded, and untrue.• Bansal and Hsu in a 2008 analysis of the long-term outcomes of patients with chronic kidney disease echoed the

observation that the disparate ESRD and mortality rates in various CKD populations as reported by various studies in the literature only emphasized the heterogeneity of CKD populations.

• No one-size-fits-all approach in medicine can be dangerous.• Patient care, more so CKD care, MUST be individualized, one CKD patient at a time.• More studies into the ramifications of these findings as they relate to CKD care, CKD planning and management call for

more studies.• Hemodialysis.com: What recommendations do you have for future research as a result of this study?• More critical investigation of longitudinal patient-level analysis of renal, morbidity and mortality outcomes among CKD

patients is needed here in the USA and worldwide.• Furthermore, the notion that CKD represented a single disease entity is dangerous and must be abandoned.• The role of the nephrologist in enhancing CKD outcomes and the role of CKD screening, we as nephrologists must

acknowledge, remain unclear and unknown, respectively, and these questions urgently demand further objective dispassionate study.

• Finally, in a recent publication, we had introduced the new concept of “Symptomatic” versus “Asymptomatic” CKD – this again calls for more studies and validation.










• REFERENCES• 1. Keith DS, Nichols GA, Gullion CM, Brown JB, Smith DH. Longitudinal follow-up and outcomes among a

population with chronic kidney disease in a large managed care organization. Arch Intern Med 2004;164:659–63.

• 2. Centers for Disease Control and Prevention (CDC): Prevalence of chronic kidney disease and associated risk factors – United States, 1999–2004. MMWR Morb Mortal Wkly Rep 2007; 56: 161–165.

• 3. Menon V, Wang X, Sarnak MJ, et al. Long-term outcomes in nondiabetic chronic kidney disease. Kidney Int 2008;73:1310–15.

• 4. Bansal N, Hsu CY. Long-term outcomes of patients with chronic kidney disease. Nat Clin Pract Nephrol 2008;4:532–3.

• 5. Onuigbo MA. The natural history of chronic kidney disease revisited–a 72-month Mayo Health System Hypertension Clinic practice-based research network prospective report on end-stage renal disease and death rates in 100 high-risk chronic kidney disease patients: a call for circumspection. Adv Perit Dial. 2009;25:85-8.

• 6. Editorial on this article. Ian H de Boer. Chronic Kidney Disease – A Challenge for all ages. JAMA 2012;308(22):2401-2402.

• 7. Moyer VA; on behalf of the U.S. Preventive Services Task Force. Screening for Chronic Kidney Disease: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2012 Aug 28. doi: 10.7326/0003-4819-157-8-201210160-00533. [Epub ahead of print].

• 8. Onuigbo MA. The CKD Enigma with Misleading Statistics and Myths about CKD, and Conflicting ESRD and Death Rates in the Literature: Results of a 2008 US Population-Based Cross-Sectional CKD Outcomes Analysis. State-of-the-Art-Review. Ren Fail. 2013 Feb 8. [Epub ahead of print].








Disentangling the Ultrafiltration Rate–Mortality Association: The Respective Roles of Session Length and Weight GainHemodialysis.com Author Interview: Dr. Jennifer E. Flythe

Renal Division, Department of Medicine, Brigham and Women’s Hospital75 Francis Street, MRB-4, Boston, MA 02115

• Hemodialysis.com: What are the main findings of the study?• Dr. Flythe: High ultrafiltration rates during hemodialysis (HD) have been

associated with increased all-cause and cardiovascular mortality. The ultrafiltration rate, however, is determined by both dialysis session length (DSL) and interdialytic weight gain (IDWG). Both short DSL and high IDWG have been linked to increased mortality, but these variables are often collinear so their independent associations with mortality have not been adequately investigated. We undertook this study to determine the associations of DSL and IDWG (independently of each other) with mortality in a population of chronic HD patients with adequate clearance.

• Our study results demonstrate that among chronic HD patients, both short DSL and high IDWG play important roles in the UFR–mortality association. Short DSL is associated with increased mortality independently of IDWG, and high IDWG is associated with increased mortality, independently of DSL. We also showed that these relationships follow dose-response patterns.


http://hemodialysis.com/disentangling-the-ultrafiltration-rate-mortality-association-the-respective-roles-of-session-length-and-weight-gain/







Renal Division, Department of Medicine, Brigham and Women’s Hospital75 Francis Street, MRB-4, Boston, MA 02115(cont)

• Hemodialysis.com: Were any of the findings unexpected?• Dr. Flythe: Interestingly, our analyses showed no statistical interaction

between DSL and IDWG, suggesting that the extension of DSL (to at least 240 minutes) would be favorable regardless of the patient’s IDWG and that limiting IDWG (to <3 kg) would be favorable regardless of the patient’s session length.


• Dr. Flythe: Since both IDWG and DSL are independently associated with mortality, targeting either (or both) may be favorable for patients. Extending DSL to at least 240 minutes and reducing weight gain to <3kg should be considered for all patients regardless of baseline adequate clearance and ambient IDWG (or DSL). One potential intervention is to titrate DSL on a session-to-session basis based on interval IDWG.








Renal Division, Department of Medicine, Brigham and Women’s Hospital75 Francis Street, MRB-4, Boston, MA 02115(cont)


• Dr. Flythe: Prospective studies of the efficacy of targeted interventions are needed. Assessment of patient opinion regarding potential interventions is also needed.

• Citation:• Disentangling the Ultrafiltration Rate–Mortality Association: The

Respective Roles of Session Length and Weight Gain• Jennifer E. Flythe, Gary C. Curhan, and Steven M. Brunelli• Disentangling the Ultrafiltration Rate–Mortality Association: The

Respective Roles of Session Length and Weight GainCJASN CJN.09460912; published ahead of print March 14, 2013, doi:10.2215/CJN.09460912







Value of Myocardial Perfusion Imaging in Renal Transplant EvaluationAngina.com Interview with: Dr. Chong Ghee ChewDepartment of Nuclear Medicine, PET and Bone Mineral Densitometry, Royal Adelaide Hospital, Adelaide, SA

• Angina.com: What are the main findings of the study?• Answer: This is a retrospective audit of the cardiac outcomes of renal failure

patients who had been transplanted in South Australia between 1999 to 2009, who had myocardial perfusion SPECT scan for the transplant assessment. The results represent ”real world” outcomes as the scans were performed in the 3 major teaching hospitals in SA. 2 endpoints – “soft” = inpatient care with angina +/- PCI +/- CABG, and “hard” = inpatient care with myocardial infarction or cardiac death. With a negative scan this cohort had a statistically significant lower soft endpoint event rate than a positive scan …3.9% vs 20.8%, hazard ratio of 4.4 at 5 years post scan. The hard endpoint event rate was also lower for those with a negative scan but the difference did not reach statistical significance. The event rates of hard and soft endpoints were no different for the negative scans that were performed with a tachycardic stress (treadmill exercise, dobutamine or external wire right atrial pacing) versus dipyridamole induced coronary vasodilatation.


http://www.angina.com/heart-and-kidney-disease/value-of-myocardial-perfusion-imaging-in-renal-transplant-evaluation/





Value of Myocardial Perfusion Imaging in Renal Transplant EvaluationAngina.com Interview with: Dr. Chong Ghee ChewDepartment of Nuclear Medicine, PET and Bone Mineral Densitometry, Royal Adelaide Hospital, Adelaide, SA (cont)

• Angina.com: Were any of the findings unexpected? • Answer: No• Angina.com: What should clinicians and patients take away from this

study?• Answer: Myocardial perfusion SPECT scan is a good predictor of cardiac

events in renal failure patients who are being considered for transplantation.

• This is a valid test for transplant assessment.• Angina.com: What further research do you recommend as a result of your

study?• The study did not include patients who were assessed but were not

transplanted. We are planning another similar audit to look at this cohort.• Citation:• ACC 2013 American College Cardiology Presentation Spring 2013For Informational Purposes Only. Not for Specific Medical Advice





Association of BP Variability with Mortality among African Americans with CKDHemodialysis.com Interview with Dr. Ciaran J. McMullan

Renal Division and Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital41 Avenue Louis Pasteur, Suite 121, Boston, MA 02115


• Dr. McMullan: A person’s blood pressure may change up and down from day to day. Some people have small day to day changes in blood pressure, and some people have large day to day changes. In a population of African Americans with kidney disease, we found that large day to day changes in blood pressure predicted a much greater risk of dying, even after controlling for other things that predict death. Thus, larger changes in blood pressure from day to day could identify a high risk group of African Americans with kidney disease; in addition, it means that scientists should examine why people have large day to day changes in blood pressure, as this may turn out to be a new area of therapy research.


http://hemodialysis.com/association-of-bp-variability-with-mortality-among-african-americans-with-ckd/%23more-509






Renal Division and Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital41 Avenue Louis Pasteur, Suite 121, Boston, MA 02115(cont)

• Hemodialysis.com: Were any of the findings unexpected?• Dr. McMullan: In our study of African Americans who had kidney disease,

we found that the people whose blood pressure changed a lot from day to day were three times more likely to die that those people whose blood pressure only changed a little. In addition, people in the group with large day to day blood pressure changes were particularly susceptible to cardiovascular deaths with rates of cardiovascular mortality almost five times that of the group with small day to day changes in blood pressure.


• Dr. McMullan: Clinicians involved in the care of patients with kidney disease should pay attention to the fluctuations seen in blood pressure measured from clinic visit to clinic visit. These fluctuations may not simply be random but may carry important information about risk.








Renal Division and Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital41 Avenue Louis Pasteur, Suite 121, Boston, MA 02115(cont)


• Dr. McMullan: We need to first understand why people’s blood pressure changes from day to day. Second, we need to understand if these ups and downs in blood pressure actually cause damage to the heart and blood vessels or, rather, are just of marker of something else that is causing damage.

• Citation:• Association of BP Variability with Mortality among African Americans

with CKD • Ciaran J. McMullan, George L. Bakris, Robert A. Phillips, and John P. Forman• Association of BP Variability with Mortality among African Americans with

CKD CJASN CJN.10131012; published ahead of print March 14, 2013, doi:10.2215/CJN.10131012







Antimicrobial Use in Outpatient Hemodialysis UnitsHemodialysis.com Interview with: Dr. Graham SnyderBeth Israel Deaconess Medical Center 110 Francis StBoston, MA 02215

• Hemodialysis.com: What are the main findings of the study?• Dr. Snyder: We looked at antimicrobial use in two Boston-area hemodialysis units in two ways: over a

nearly three-year retrospective time period, we calculated the total amount of antimicrobials used, and prospectively over a one-year time period we analyzed each dose of parenteral antimicrobial administered in the hemodialysis units.

• Over a 35-month retrospective period there were over 2,300 antimicrobial doses given in the two hemodialysis units, which equates to an overall antimicrobial use rate of 33 doses per 100 patient-months. For any given month, the range of antimicrobial use was between 5 doses and 67 doses per 100 patient-months. Vancomycin was the most commonly administered antimicrobial, accounting for approximately two-thirds of doses (overall, 22 doses per 100 patient-months), followed by cefazolin (5 doses per 100 patient-months) and third/fourth-generation cephalosporins (3 doses per 100 patient-months); other antimicrobials were given less frequently.In the 12-month prospective period, we followed 278 patients in the two hemodialysis units, 89 (32%) of whom received at least one parenteral dose of antimicrobial. Of the 1,003 doses given during that time, we could determine the appropriateness of indication in 926 (92%). Nearly 30% (276/926) of these doses had an inappropriate indication, including prescribing for conditions not meeting guidelines-based criteria to diagnose infection (146, 53%), use when a more narrow spectrum antimicrobial could have been chosen (74, 27%), and for surgical prophylaxis beyond recognized indication for prophylaxis (58, 20%). Over one-third of vancomycin and third/fourth-generation cephalosporin doses were inappropriately indicated.


http://hemodialysis.com/antimicrobial-use-in-outpatient-hemodialysis-units/%23more-503







Antimicrobial Use in Outpatient Hemodialysis UnitsHemodialysis.com Interview with: Dr. Graham SnyderBeth Israel Deaconess Medical Center 110 Francis StBoston, MA 02215(cont)

• Hemodialysis.com: Were any of the findings unexpected?• Dr. Snyder: To date, there has been very little data reported on antimicrobial prescribing practices in

the hemodialysis setting.• From nationwide data collected through the United States Renal Data System (USRDS), we know that

approximately 40% of patients receiving chronic hemodialysis have at least one billing claim for an antimicrobial each year, and that vancomycin constitutes about two-thirds of prescribed antimicrobials. Our data showing that approximately 32% of patients receive a parenteral dose of antimicrobials and approximately two-thirds of the antimicrobial doses are vancomycin is consistent with USRDS data.

• Lastly, two prior studies (Green K, Am J Kidney Dis 2000;35:64-68; Zvonar R, Nephrol Dial Transplant 2008;23:3690-3695) have shown that for vancomycin, at least 10-33% of antimicrobials are inappropriately indicated, and most frequently for not choosing an antimicrobial with a more narrow spectrum of activity and for treating conditions unlikely to be a true infection.

• The data from our study is in agreement with these findings, and expands on the findings in these studies. A significant novel finding of our study was the substantial (and frequently inappropriately indicated) use of third/fouth-generation cephalosporins.

• This is important because based on USRDS data the use of these agents is increasing, and the use of these agents relates very closely to antimicrobial resistant gram-negative bacterial infections, which have a high and increasing prevalence among the dialysis population.








• Hemodialysis.com: What should clinicians and patients take away from this study?• Dr. Snyder: There is room for improvement in antimicrobial prescribing practices, including

reducing use when not indicated and choosing the most appropriate antimicrobial for a given infectious condition.

• In addition to minimizing the risk of adverse effects directly attributable to the antimicrobials, limiting inappropriate use of antimicrobials has the potential to lead to a decrease in the emergence and spread of antimicrobial resistant bacteria among patients receiving hemodialysis. This effect on resistant bacteria may subsequently reduce the spread of these bacteria from patients receiving hemodialysis to other hospitalized patients and individuals in the community as well.


• Dr. Snyder: In addition to confirming these findings in other hemodialysis populations, our results may be used to help tailor antimicrobial stewardship interventions.

• Interventions particularly worthy of investigation may include vancomycin and cephalosporin prescribing, decision support for surgical prophylaxis, and clinical management of skin/soft tissue infections. Future studies may identify patient populations among those receiving chronic hemodialysis who are particularly likely to receive antimicrobials and inappropriately indicated antimicrobials, and therefore also guide antimicrobial stewardship efforts.








• Citation:• Antimicrobial Use in Outpatient Hemodialysis Units• Snyder GM, Patel PR, Kallen AJ, Strom JA, Tucker JK,

D’Agata EM.• Division of Infectious Diseases, Beth Israel

Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.Infect Control Hosp Epidemiol. 2013 Apr;34(4):349-57. doi: 10.1086/669869. Epub 2013 Feb 18.







Cinacalcet Improves Endothelial Dysfunction and Cardiac Hypertrophy in Patients on Hemodialysis with Secondary Hyperparathyroidism

Hemodialysis.com Interview with: Cheol Whee Park, M.D.Professor of Internal Medicine Seoul St. Mary’s HospitalDivision of Nephrology, Department of Internal Medicine The Catholic University of KoreaSeoul, Republic of Korea


• Answer: Secondary hyperparathyroidism (SHPT) is a common complication of end-stage renal failure and it is associated with high morbidity and mortality. Furthermore, SHPT affects the cardiovascular system related to cardiovascular calcification and cardiomyopathy. The calcium-sensing receptor (CaSR) is expressed in cardiomyocytes, endothelial cells and vascular smooth muscle cells, which raises the possibility that this receptor may be implicated in the pathophysiology of cardiovascular disease and constitute a potential therapeutic target.

• The recently published EVOLVE trial did not support the notion that cinacalcet, a calcimimetic of the second generation, reduces the risk of death or major cardiovascular event in hemodialysis patients with moderate-to-severe secondary hyperparathyroidism (SHPT). However, the findings from the EVOLVE trial are probably inconclusive because of low statistical power. Therefore, important questions regarding the clinical benefits of cinacalcet on cardiovascular system in hemodialysis patients in the setting of SHPT are remained to solve.

• In this regard, our prospective, open-labeled, controlled, crossover clinical study found that cinacalcet hydrochloride treatment without vitamin D ameliorates endothelial dysfunction and inflammation, cardiac diastolic dysfunction, and cardiac hypertrophy by decreasing oxidative stress and improving endothelial dysfunction with increasing the serum nitric oxide (NOx) production in hemodialysis patients with SHPT.


http://hemodialysis.com/cinacalcet-improves-endothelial-dysfunction-and-cardiac-hypertrophy-in-patients-on-hemodialysis-with-secondary-hyperparathyroidism/

















Hemodialysis.com Interview with: Cheol Whee Park, M.D.Professor of Internal Medicine Seoul St. Mary’s HospitalDivision of Nephrology, Department of Internal Medicine The Catholic University of KoreaSeoul, Republic of Korea(cont)

• Hemodialysis.com: Were any of the findings unexpected?• Answer: We were interested in the evidence that cinacalcet without Vit D could improve vascular endothelial

dysfunction and inflammation.• The combination treatment with cinacalcet and low dose vitamin D are found to be associated with the

attenuation of cardiovascular calcification in hemodialysis patients; however, the effects of cinacalcet alone (without vitamin D) on cardiac and endothelial functions have not been well defined in hemodialysis patients with SHPT. In contrast, we demonstrated that cinacalcet along significantly improves vascular endothelial dysfunction and inflammation, diastolic cardiac dysfunction, and LVH. These findings suggest that cinacalcet itself might improve the endothelial dysfunction, arterial stiffness and cardiac diastolic dysfunction, and left ventricular hypertrophy related to ameliorate oxidative stress and NOx production in the hemodialysis patients with SHPT. Recent studies also demonstrated that cinacalcet protects vascular damage in the nerve by improving NOx production and vasodilation.

• Hemodialysis.com: What should clinicians and patients take away from this study?• Answer: Despite effective improvement of biochemical parameters of dialysis patients with SHPT, the intention-

to-treat analysis of the EVOLVE trial did not support the notion that cinacalcet significantly reduces the risk of death or major cardiovascular events in dialysis patients with moderate-to-severe SHPT. In contrast, the simultaneous reduction of serum calcium, phosphorus and intact parathyroid hormone (iPTH) as well as the increased CaSR in the cardiovascular system are favorable mechanisms for attenuating the progression of vascular calcification and cardiac hypertrophy in dialysis patients with SHPT. Our study added some favorable data to the question regarding whether cinacalcet without Vit D might reduce oxidative stress and improve endothelial function in hemodialysis patients in SHPT.












Hemodialysis.com Interview with: Cheol Whee Park, M.D.Professor of Internal Medicine Seoul St. Mary’s HospitalDivision of Nephrology, Department of Internal Medicine The Catholic University of KoreaSeoul, Republic of Korea(cont)


Answer: Our study has some limitations including the small number of study patients and the short time interval of the study period. Therefore, a prospective, multicenter, large-scale study with a longer follow-up period is required to yield more informative data in terms of the cardiovascular effects of cinacalcet. Researches are also needed to assess the cinacalcet treatment commonly used in hemodialysis patients with SHPT over a broad spectrum of SHPT. Moreover, future randomized controlled and open label extension trials are needed to directly evaluate the long-term comparative effects of cinacalcet along or with Vit D (or analogues) in hemodialysis patients with SHPT.

• Citation:• Cinacalcet Improves Endothelial Dysfunction and Cardiac Hypertrophy in Patients on

Hemodialysis with Secondary HyperparathyroidismChoi S.R. · Lim J.H. · Kim M.Y. · Hong Y.-A. · Chung B.H. · Chung S. · Choi B.S. · Yang C.W. · Kim Y.-S. · Chang Y.S. · Park C.W.Nephron Clin Pract 2012;122:1-8 (DOI: 10.1159/000347145)











Renal anaemia and EPO hyporesponsiveness associated with vitamin D deficiency: the potential role of inflammationHemodialysis.com Authors’ Interview: Dr Andrea IcardiNephrology and Dialysis Unit, La Colletta and Villa Scassi Hospitals ASL 3,

Arenzano and Genoa, ItalyCorresponding Author: Dr. Mario Cozzolino, MD, PhDAssistant Professor in NephrologyDepart. of Health Sceinces- School of Medicine University of Milan Renal Division – San Paolo Hospital Milan – Italy

• Hemodialysis.com: What are the main findings of the study?• Response: Our review of the literature data findings concentrates on the central role of

inflammation in the inhibition of erythropoiesis and iron availability in CKD patients with EPO-resistant anemia associated with vitamin D deficiency. This inflammatory action is mediated by suppressive cytokines (i.e. IL-6, TNF-α, INF-γ) inhibiting differentiation and proliferation activities of erythroid cells in the EPO-independent phase of erythropoiesis and stimulating hepcidin production for iron retention in the reticuloendothelial system and enterocytes.

• Vitamin D is a well-known regulator of the immune system. In the bone marrow micro-environment, VDRs activation reduces pro-inflammatory cytokines signaling and up-regulates the lymphocytic release of IL-10, exerting both anti-inflammatory and proliferative effects on erythroid cascade. In the late phase of erythropoiesis, anti-IL-6 expression by activated VDRs may decrease hepcidin over-production.

• Vitamin D deficiency has been linked with anemia and EPO hyporesponsiveness in CKD patients and the inverse correlation of vitamin D levels with inflammation status has been reported. Our study identifies vitamin D deficiency such as a possible new pathophysiological co-factor of renal anemia of inflammation and suggests a pleiotropic action of vitamin D and analogues on erythropoiesis and iron balance.


http://hemodialysis.com/renal-anaemia-and-epo-hyporesponsiveness-associated-with-vitamin-d-deficiency-the-potential-role-of-inflammation/%23more-479




























Renal anaemia and EPO hyporesponsiveness associated with vitamin D deficiency: the potential role of inflammationHemodialysis.com Authors’ Interview: Dr Andrea Icardi

Nephrology and Dialysis Unit, La Colletta and Villa Scassi Hospitals ASL 3, Arenzano and Genoa, ItalyCorresponding Author: Dr. Mario Cozzolino, MD, PhDAssistant Professor in Nephrology

Depart. of Health Sceinces- School of Medicine University of Milan Renal Division – San Paolo Hospital Milan – Italy (cont)

• Hemodialysis.com: What should clinicians and patients take from your review?

• Response: EPO resistance is associated with adverse outcomes, such as CVD, faster progression to ESRD and mortality. Treatment of the causes of EPO hyporesponsiveness including chronic inflammation results in an improvement of anemia and a reduction in EPO requirements. In CKD patients effective vitamin D axis preservation may be crucial not only for bone and mineral metabolism, but also for the effects on many organs and biological activities, including hemopoietic system and iron utilization.

• Hemodialysis.com: What future research do you suggest as a result of your study?• Response: The association of vitamin D supplementation with the improvement of renal

anemia and EPO resistance seems to be independent of PTH suppression and an activation of 1α-hydroxylase enzyme in the bone marrow is only one hypothesis.

• The majority of reports suggest the central role of inflammation in the mechanism underlying this relationship. However, no RCTs are available regarding the effects of native vitamin D, calcitriol or analogues on hemoglobin and inflammatory markers as main outcome measures in CKD. Future interventional studies are needed to demonstrate the therapeutic use of these agents in renal anemia and EPO hyporesponsiveness.











Renal anaemia and EPO hyporesponsiveness associated with vitamin D deficiency: the potential role of inflammationHemodialysis.com Authors’ Interview: Dr Andrea Icardi

Nephrology and Dialysis Unit, La Colletta and Villa Scassi Hospitals ASL 3, Arenzano and Genoa, ItalyCorresponding Author: Dr. Mario Cozzolino, MD, PhDAssistant Professor in Nephrology

Depart. of Health Sceinces- School of Medicine University of Milan Renal Division – San Paolo Hospital Milan – Italy (cont)

• Citation:• Renal anaemia and EPO hyporesponsiveness

associated with vitamin D deficiency: the potential role of inflammationAndrea Icardi, Ernesto Paoletti, Luca De Nicola, Sandro Mazzaferro, Roberto Russo, and Mario Cozzolino

• Nephrol. Dial. Transplant. first published online March 6, 2013 doi:10.1093/ndt/gft021











Survival and heart failure therapy in chronic dialysis patients with heart failure and reduced left ventricular ejection fraction:Hemodialysis.com Interview with: Dr. Derthoo

Department of Cardiovascular Medicine, University Hospitals Leuven, Leuven, Belgium.(cont)

• Hemodialysis.com: What are the main findings of the study?• Dr. Derthoo : We retrospectively followed 250 patients who started dialysis between 2005 and 2009 to clarify

the prevalence, the prognosis and the prescribed heart failure treatment of systolic heart failure patients on dialysis. The main findings are:

• 1/ Heart failure with reduced left ventricular ejection fraction (HFREF) is an independent predictor of worse outcome. Especially patients with a left ventricular ejection fraction (LVEF) < 30% had an increased cardiovascular mortality early after initiation of dialysis. The most frequent causes of death were infections, cardiac arrhythmias and progressive heart failure. In group of patients with HFREF, 32% of the patients died due to infections, 29% due to cardiac arrhythmias and 16% due to progressive heart failure.

• 2/ The prevalence of a LVEF ≤ 45% was 18% in this population (n = 45). We excluded patients who underwent renal transplantation during follow-up. Patients with systolic LV dysfunction represent an important subgroup in a chronic dialysis population. This subgroup probably needs a more individualized and maybe a different management than dialysis patients without LV dysfunction. Unfortunately most of these patients are lost from cardiologic follow-up.

• 3/ Chronic heart failure therapy in non-dialysis patients is mainly focused on neurohormonal blockade with ACE-inhibitors (or angiotensin-receptor blockers), beta-blockers and aldosteron-antagonists. In our dialysis population most patients received suboptimal or even no heart failure treatment. Only 27% of our heart failure patients were treated with the combination of RAAS-inhibitors and beta-blockers, while 18% did not receive any of these medications. The prescribed dose was also low in most patients. None of the patients was treated with spironolactone or eplerenon.




Department of Cardiovascular Medicine, University Hospitals Leuven, Leuven, Belgium.

• Hemodialysis.com: Were any of the findings unexpected?• Dr. Derthoo : Most of the findings could have been

expected. It is well known that a reduced LVEF is an independent risk factor for increased mortality. The most striking finding was mainly that heart failure treatment in this population was so neglected and suboptimal. These patients have a high cardiovascular mortality, especially those with a LVEF < 30%. Our findings show that there are still opportunities to improve the prognosis of heart failure patients on dialysis by using standard treatment with neurohormonal blockers.






• Dr. Derthoo : Heart failure is a condition that leads to in important neurohormonal activation (of the renin-angiontensin-aldosteron system and the sympathetic system). This causes progressive adverse LV remodeling, heart failure and cardiovascular morbidity and mortality. Even after initiation of dialysis this neurohormonal overdrive persists and these patients should be treated with neurohormonal blockers.

• Unfortunately this appears to be often neglected or impossible in clinical practice, mainly due to the occurrence of hypotension during dialysis. A difficult issue remains to estimate the ‘dry weight’ correctly. Too aggressive ultrafiltration and a too low ‘dry weight’ causes hypotension in some heart failure patients on dialysis. Some patients might benefit from more frequent en longer ultrafiltration.

• There is little evidence from clinical trials in this population. Only the group of Cice et al. performed a few randomized trials using ACE-inhibitors plus carvedilol (J Am Coll Cardiol 2001 ;37:407?11. and J Am Coll Cardiol 2003 ;41:1438?44.) and even ACE-inhbitors plus telmisartan plus carvedilol (J Am Coll Cardiol 2010 ;56:1701-8.), showing a significant reduction of cardiovascular morbidity and mortality. Especially the use of carvedilol and telmisartan in this population is appealing, because these products have minimal renal excretion and no dose adjustments are required in patients with end-stage renal disease.






• Dr. Derthoo : More randomized controlled trials are needed to confirm the findings of Cice et al. In their study, they managed to treat their patients with full dose neurohormonal blockade. The feasibility of this combination therapy sometimes appears to be questionable in clinical practice.

• Another appealing treatment is the introduction of aldosteron-antagonists (spironolacton3) in this dialysis population. Smaller studies show an acceptable safety profile without a significant increase in hyperkalemia.

• There are also more prospective studies needed to assess how we can estimate the dry weight more correctly and how this correlates with intracardiac filling pressures.

• As studies and clinical evidence in this population is still scarce, a lot of questions remain unanswered.





• Survival and heart failure therapy in chronic dialysis patients with heart failure and reduced left ventricular ejection fraction: an observational retrospective study.

• Derthoo D, Belmans A, Claes K, Bammens B, Ciarka A, Droogné W, Vanhaecke J, Van Cleemput J, Janssens S.

• Department of Cardiovascular Medicine, University Hospitals Leuven, Leuven, Belgium.

• Acta Cardiol. 2013 Feb;68(1):51-7For Informational Purposes Only. Not for Specific Medical Advice


Predicting the prevalence of chronic kidney disease in the English populationHemodialysis.com Author Interview: Ben Kearns, MSc.

Research Associate, School of Health and Related Research, The University of Sheffield, United Kingdom

• Hemodialysis.com: What are the main findings of the study?• Ben Kearns: We used a large, representative sample of adults in

England, and were able to identify undiagnosed cases of CKD. We found a sample prevalence for CKD of 6.76%; much greater than the reported national prevalence of 4.3%. The prevalence of diagnosed CKD in our sample was 3.9%; indicating that about two in every five patients with CKD are unknown to their doctor.

• We developed statistical models to predict the overall prevalence of CKD. We identified increasing age, female gender and the presence of cardiovascular disease as all being risk factors that increased the odds of having CKD. In addition, we noticed that cardiovascular disease was a stronger risk factor amongst younger patients than it was amongst older patients.


http://hemodialysis.com/predicting-the-prevalence-of-chronic-kidney-disease-in-the-english-population/%23more-465





Research Associate, School of Health and Related Research, The University of Sheffield, United Kingdom(cont)

• Hemodialysis.com: Were any of the findings unexpected?• Ben Kearns: There is a rich literature on predictors for CKD. Increasing age, female gender

and the presence of cardiovascular disease have all previously been identified as predictors. Whilst confirming this, we also found an unexpected interaction between cardiovascular disease and age; the increase in the probability of having CKD due to having a cardiovascular disease was much greater amongst younger patients than amongst older patients. To our knowledge this is the first time this interaction has been identified in the literature.

• Because of its largely asymptomatic nature, there has been a long-standing worry that many cases of CKD remain undiagnosed. However, the extent of this has been largely unknown – we have been able to quantify this.

• Hemodialysis.com: What should clinicians and patients take away from your report? • Ben Kearns: A high proportion of patients with CKD are currently undiagnosed. Using the

results of our report, it is possible to identify areas where the predicted prevalence of CKD is much greater than the diagnosed prevalence. These areas may be targeted for local campaigns to raise the awareness of CKD. It is also possible to use the results of our report to identify groups at particular risk of having CKD.







Research Associate, School of Health and Related Research, The University of Sheffield, United Kingdom(cont)


• Ben Kearns: The identified interaction between age and cardiovascular disease could be very important. This feature of the study was not anticipated in advance, so future research to confirm this feature is important.

• Research into the areas which have particularly high levels of undiagnosed CKD and the reasons for these would also be worthwhile.

• Reference:• Predicting the prevalence of chronic kidney disease in the English

population: a cross-sectional study• BMC Nephrology 2013, 14:49• Kearns B, Gallagher H, de Lusignan S.

Full text freely available at: http://www.biomedcentral.com/1471-2369/14/49






Effective elimination of dabigatran by haemodialysis. A phase I single-centre study in patients with end-stage renal diseaseHemodialysis.com Interview with Prof. Dr. med. Harm PetersProjektsteuerung Modellstudiengang Medizin &Nephrologie Charité

Universitätsmedizin Berlin, Campus Charité Mitte 10117 Berlin

• Hemodialysis.com: What are the main findings of the study?• Dr. Peters: The four key findings from our study are as follows:• 1) in ESRD patients, a specific dosing regimen (150 mg on Day 1, 110 mg on

Day 2 and 75 mg on Day 3) yielded peak dabigatran plasma concentrations on Day 3 comparable to those observed in AF patients with atrial fibrillation in RE-LY dosed with 150 mg b.i.d.; however, it could not be considered as a suitable treatment regimen for ESRD patients undergoing regular HD and who are in need of regular anticoagulation.

• 2) a single 4-hour hemodialysis session removed 48.8% of plasma dabigatran at a blood flow rate of 200 ml/min and 59.3% at blood flow rates of 350-395 ml/min;

• 3) the anticoagulant activity of dabigatran was reduced proportionally to the hemodialysis-related reduction in plasma levels;

• 4) a minor redistribution of dabigatran (7.5-15%) into the plasma compartment was noted after the end of dialysis.


http://hemodialysis.com/effective-elimination-of-dabigatran-by-haemodialysis-a-phase-i-single-centre-study-in-patients-with-end-stage-renal-disease/
























Universitätsmedizin Berlin, Campus Charité Mitte 10117 Berlin(cont)


• Dr. Peters: The previous study from Stangier J et al. included six patients with end-stage renal failure who were given a single 50 mg dose of dabigatran at the commencement of a 4 hour hemodialysis session. There was elimination rate of 62-68% of dabigatran observed. Thus, the findings of our study are not unexpected.

• However, the study of Stangier et al did not reveal the fraction of dabigatran cleared from the plasma. More over there was not clear whether the hemodialysis session would be able to effectively reduce the dabigatran in concentration comparable to those observed in patients with atrial fibrillation dosed with 150 mg twice daily.

• Hemodialysis.com: What should clinicians and patients take away from your report?• Dr. Peters: A 4-hour hemodialysis session can rapidly eliminate at least half of the dabigatran

in the central compartment with an important reduction in its anticoagulant activity. This is important because there is currently no available antidote to reverse the anticoagulant effects of dabigatran, which is being increasingly used globally. Patients taking and physicians prescribing dabigatran can be aware there is a method to potentially reduce its anticoagulant effects in critical situations.









Universitätsmedizin Berlin, Campus Charité Mitte 10117 Berlin(cont)


• Dr. Peters: Based on the available data no final assessment can be made if this magnitude of redistribution might change once extreme (e.g. accidental or suicidal) supra-therapeutic plasma concentrations are present after multiple dosing. Besides the study population consisted of clinical stable patients with relatively few co-morbidities other than their ESRD and its expected consequences. Thus, the therapeutic benefit of dialysis still requires confirmation in patients with bleeding complications or other emergency situations.

• Citation:• Effective elimination of dabigatran by haemodialysis. A phase I single-centre study in

patients with end-stage renal disease• Harm Peters, MD, Department of Nephrology, Charité – Universitätsmedizin Berlin,

Humboldt University, Charitéplatz 1, 10117 Berlin, Germany, Tel.: +49 30 450 514072, Fax: +49 30 450 514902

• Khadzhynov D, Wagner F, Formella S, Wiegert E, Moschetti V, Slowinski T, Neumayer HH, Liesenfeld KH, Lehr T, Härtter S, Friedman J, Peters H, Clemens A.

• Thromb Haemost. 2013 Feb 7;109(4). [Epub ahead of print]








Feasibility of catheter-based renal nerve ablation and effects on sympathetic nerve activity and blood pressure in patients with ESRD

Hemodialysis.com Interview with: Professor Markus SchlaichMD, Nephrologist & Hypertension Specialist Adjunct Professor, Central Clinical SchoolFaculty of Medicine, Nursing & Health Sciences, Monash University NHMRC

Senior Research FellowHead, Neurovascular Hypertension & Kidney Disease Baker IDI Heart and Diabetes Institute75 Commercial Road, Melbourne VIC 3004

• Hemodialysis.com: What are the main findings of the study? • Professor Schlaich: This was a small proof-of concept and feasibility study

to explore the usefulness of renal denervation in patients with ESRD on maintenance haemodialysis and uncontrolled blood pressure despite the use of an average of 3.8+/-1.4 antihypertensive drugs.

• The subset of patients who had assessment of sympathetic nerve activity displayed substantially elevated sympathetic tone. Renal denervation could be performed in 9 out of 12 patients. Three patients had renal artery diameters there were deemed too small to be treated. Compared to baseline, office systolic BP was significantly reduced at 3, 6, and 12 months after RDN (from 166±16.0 to 148±11, 150±14, and138±17mmHg, respectively), whereas no change was evident in the 3 non-treated patients. Sympathetic nerve activity was substantially reduced in 2 patients who underwent repeat assessment.


http://hemodialysis.com/feasibility-of-catheter-based-renal-nerve-ablation-and-effects-on-sympathetic-nerve-activity-and-blood-pressure-in-patients-with-esrd/


















Hemodialysis.com Interview with: Professor Markus SchlaichMD, Nephrologist & Hypertension Specialist Adjunct Professor, Central Clinical School

Faculty of Medicine, Nursing & Health Sciences, Monash University NHMRC Senior Research FellowHead, Neurovascular Hypertension & Kidney Disease Baker IDI Heart and Diabetes Institute

75 Commercial Road, Melbourne VIC 3004(cont)


Professor Schlaich: Diameter of the renal arteries in some of the patients were too small to be treated with the renal denervation catheter system available at the time. This may be a common problem, which potentially can be overcome by further technical developments and specifically designed catheters.

• Hemodialysis.com: What should clinicians and patients take away from your report?• Professor Schlaich: This is an initial and encouraging proof of concept study to

demonstrate that renal denervation can be applied safely and reduces both blood pressure and sympathetic nerve activity in patients with ESRD.

• These initial results are uncontrolled and obtained in a small series of patients and therefore require confirmation in larger and adequately controlled clinical trials. At this stage, renal denervation should only be considered in ESRD patients with uncontrolled blood pressure who have failed all other measures of lowering blood pressure. The procedure should only be performed in experienced centres. Renal artery imaging with exact assessment of the renal artery diameter is warranted before considering the procedure.











Hemodialysis.com Interview with: Professor Markus SchlaichMD, Nephrologist & Hypertension Specialist Adjunct Professor, Central Clinical School

Faculty of Medicine, Nursing & Health Sciences, Monash University NHMRC Senior Research FellowHead, Neurovascular Hypertension & Kidney Disease Baker IDI Heart and Diabetes Institute

75 Commercial Road, Melbourne VIC 3004(cont)


• Professor Schlaich: Ideally, an adequately sized randomized controlled clinical trial should be performed to assess the safety, efficacy, and long term consequences of catheter-based renal denervation in patients with ESRD.

• Citation:• Feasibility of catheter-based renal nerve ablation and effects on sympathetic nerve

activity and blood pressure in patients with end-stage renal disease.• Schlaich MP, Bart B, Hering D, Walton A, Marusic P, Mahfoud F, Böhm M, Lambert EA,

Krum H, Sobotka PA, Schmieder RE, Ika-Sari C, Eikelis N, Straznicky N, Lambert GW, Esler MD.

• Int J Cardiol. 2013 Feb 28. pii: S0167-5273(13)00278-7. doi: 10.1016/j.ijcard.2013.01.218. [Epub ahead of print]

• Neurovascular Hypertension & Kidney Disease and Human Neurotransmitters Laboratories Baker IDI Heart & Diabetes Institute, Alfred Hospital, Melbourne, Australia; Heart Centre, Alfred Hospital, Melbourne, Australia; Faculty of Medicine, Nursing and Health Sciences and Department of Physiology, Monash University, Melbourne, Victoria, Australia.










Lethal cardiac arrhythmia during central venous catheterization in a uremic patientHemodialysis.com Interview with Jer-Ming Chang. MD. PhD

Secretary for the Superintendant, and Attending physician, Department of Internal MedicineKaohsiung Municipal Hsiao-Kang HospitalAssociate professor, College of Medicine, Kaohsiung Medical University Attending physician

Division of Nephrology, Kaohsiung Medical University Hospital Kaohsiung 807, Taiwan

• Hemodialysis.com: What are the main findings of the study?• Dr. Chang: Cardiac arrhythmia induced during the procedure

of central vein catheterization might be more common than expected, especially in high-risk CKD patients (pre-existing CV diseases, electrolytes disturbances…).Continuous monitoring during procedure is recommended for safety.

• Hemodialysis.com: Were any of the findings unexpected?• Dr. Chang: Most of these unexpected arrhythmic events can

be salvaged properly, unless unnoticed.


http://hemodialysis.com/lethal-cardiac-arrhythmia-during-central-venous-catheterization-in-a-uremic-patient/









Lethal cardiac arrhythmia during central venous catheterization in a uremic patientHemodialysis.com Interview with Jer-Ming Chang. MD. PhD

Secretary for the Superintendant, and Attending physician, Department of Internal MedicineKaohsiung Municipal Hsiao-Kang HospitalAssociate professor, College of Medicine, Kaohsiung Medical University Attending physician

Division of Nephrology, Kaohsiung Medical University Hospital Kaohsiung 807, Taiwan(cont)


• Dr. Chang: Unfortunately this is an undisputable safety issue and may not be suitable for study.

• Citation:• Lethal cardiac arrhythmia during central venous

catheterization in a uremic patient: A case report and review of the literature

• Huang, Y.-C., Huang, J.-C., Chen, S.-C., Chang, J.-M. and Chen, H.-C. (2013), Hemodialysis International. doi: 10.1111/hdi.12030









Statin Use and Calcific Uremic Arteriolopathy: A Matched Case-Control StudyHemodialysis.com Interview with Dr. Sagar U. NigwekarMassachusetts General Hospital, Bulfinch 127, Boston, MA 02114

• Hemodialysis.com: What are the main findings of the study?• Dr. Nigwekar: Calcific uremic arteriolopathy (a.k.a. calciphylaxis) is a

rare but life threatening disease generally seen in hemodialysis patients. It is characterized by calcification, severe inflammation and clot formation in skin tissue.

• Our case-control study addressed whether statins with their anti-inflammatory, anti-thrombotic and anti-calcification properties are able to reduce the risk of calcific uremic arteriolopathy in hemodialysis patients. We observed that statin use is associated with over 60% reduction in the risk of calcific uremic arteriolopathy in both unadjusted and adjusted analyses. Higher calcium level, lower albumin level and warfarin use were other notable risk factors. This is one of the largest studies on calcific uremic arteriolopathy.


http://hemodialysis.com/statin-use-and-calcific-uremic-arteriolopathy-a-matched-case-control-study/









Statin Use and Calcific Uremic Arteriolopathy: A Matched Case-Control StudyHemodialysis.com Interview with Dr. Sagar U. NigwekarMassachusetts General Hospital, Bulfinch 127, Boston, MA 02114(cont)


• Dr. Nigwekar: Yes. We had 2 unexpected findings- one related to vitamin D compounds and the other regarding incidence of calcific uremic arteriolopathy.

• Vitamin D compounds are commonly implicated in vascular calcification. We observed that there are differences in the risk of calcific uremic arteriolopathy with different classes of active vitamin D compounds. Risk of calcific uremic arteriolopathy was higher with calcitriol use but not with selective vitamin D analogues such as paricalctiol and doxerecalciferol.

• We also observed significant increase in the incidence of calcific uremic arteriolopathy over the last decade. Reasons for this rise remain under investigation.


• Dr. Nigwekar: Calcific uremic arteriolopathy should be considered whenever a dialysis patient is presenting with skin lesions associated with severe pain. Statins, although have not shown to be effective in dialysis patients to reduce mortality, should be considered in management of dialysis patients for their potential to reduce the risk of calcific uremic arteriolopathy. Attention should also be paid to effective management of nutritional status, calcium metabolism and careful risk-benefit analysis is warranted for warfarin therapy in dialysis.






Statin Use and Calcific Uremic Arteriolopathy: A Matched Case-Control StudyHemodialysis.com Interview with Dr. Sagar U. NigwekarMassachusetts General Hospital, Bulfinch 127, Boston, MA 02114(cont)


• Dr. Nigwekar: Large prospective studies are needed to confirm associations observed in our study.

• At present there are no effective preventive strategies for calcific uremic arteriolopathy and statins, if confirmed in future studies, will offer a novel method to reduce the risk of this devastating condition.

• Sodium Thiosulfate Therapy for Calcific Uremic Arteriolopathy • Nigwekar S.U. · Bhan I. · Turchin A. · Skentzos S.C. · Hajhosseiny R. ·

Steele D. · Nazarian R.M. · Wenger J. · Parikh S. · Karumanchi S.A. · Thadhani R.Am J Nephrol 2013;37:325-332 (DOI:10.1159/000348806)






Sodium Thiosulfate Therapy for Calcific Uremic ArteriolopathyHemodialysis.com Interview with Dr. Sagar U. NigwekarMassachusetts General Hospital, Bulfinch 127, Boston, MA 02114

• Hemodialysis.com: What are the main findings of the study?• Dr. Nigwekar : Calcific uremic arteriolopathy is a rare but life-threatening

condition in hemodialysis patients. Ours is the largest-to-date study that systematically examined outcomes in patients with calcific uremic arteriolopathy treated with intravenous sodium thiosulfate. Effectiveness and safety in this cohort study were assessed by conducting surveys of treating physicians and by reviewing electronic records.

• We observed that majority of patients (>70%) demonstrated improvement in skin lesions. Mortality rate in patients treated with sodium thiosulfate was noted to be lower than historical published data in patients not treated with sodium thiosulfate. Sodium thiosulfate had mild adverse effect profile in this setting. Study limitations include its observational nature, low survey response rate, and inability to assess long term safety profile of sodium thiosulfate.


http://hemodialysis.com/sodium-thiosulfate-therapy-for-calcific-uremic-arteriolopathy/








Sodium Thiosulfate Therapy for Calcific Uremic ArteriolopathyHemodialysis.com Interview with Dr. Sagar U. NigwekarMassachusetts General Hospital, Bulfinch 127, Boston, MA 02114(cont)

• Hemodialysis.com: Were any of the findings unexpected?• Dr. Nigwekar : Despite significant sodium overload that is

associated with sodium thiosulfate treatment and potential for acidosis, overall adverse event profile (post dialysis weight gain, metabolic acidosis) was mild. Long term adverse event profile of sodium thiosulfate remains unknown.

• In addition, we observed significant reductions in serum phosphorous and parathyroid hormone levels with sodium thiosulfate treatment. However, our study could not conclusively attribute these changes to sodium thiosulfate treatment since there were co-treatments that may have influenced these parameters.








• Dr. Nigwekar : Calcific uremic arteriolopathy is a highly devastating condition with significant morbidity and mortality. Based on our findings regarding effects of sodium thiosulfate treatment on skin lesions and mortality, we suggest that intravenous sodium thiosulfate should be considered in management of calcific uremic arteriolopathy. Patients and clinicians should be aware of commons side effects of sodium thiosulfate such as nausea, vomiting, and bad taste but will be encouraged to know that these are mild and temporary.

• It is important to note that there are no other effective treatments for this condition and given the rarity of disease, randomized controlled trial to address any intervention in this study is highly challenging.








• Dr. Nigwekar : Intravenous sodium thiosulfate has recently been in a short supply and also has cost-implications. In that setting it will be important to develop a prediction score tool that distinguishes patients that are likely to respond to this treatment.

• Effects of other treatments (such as cinacalcet) along with sodium thiosulfate also need to be examined in future studies.

• Citation:• Sodium Thiosulfate Therapy for Calcific Uremic Arteriolopathy• Sagar U. Nigwekar, Steven M. Brunelli, Debra Meade, Weiling Wang,

Jeffrey Hymes, and Eduardo Lacson, Jr• CJASN CJN.09880912; published ahead of print March 21, 2013,

doi:10.2215/CJN.09880912For Informational Purposes Only. Not for Specific Medical Advice





The MONitoring Dialysis Outcomes (MONDO) initiative.Hemodialysis.com Interview with Dr.Len Usvyat PhDDirector, Integrated Care AnalyticsRenal Research InstituteFresenius Medical Care

• Hemodialysis.com: What are the main findings of the study?Dr. Usvyat: MONDO (MONitoring Dialysis Outcomes) is an international consortium of dialysis providers who contribute both patient data and analytical resources to study this global database with aims of understanding and improving outcomes in patients with end stage kidney disease world-wide. While its initial focus was on studying “trajectories of patient parameters before death,” it has much expanded since then. MONDO comprises of longitudinal, patient specific data from 5 continents, 38 countries, ~1200 clinics, ~150,000 patients, and ~30,000,000 hemodialysis treatments between 2000 and 2012. Its data is updated annually and will soon include PD patients as well.

• Hemodialysis.com: Were any of the findings unexpected?Dr. Usvyat: So far, we found that longitudinal patient parameters before death appear remarkably similar from one database to another irrespective of the background demographic differences. While many variations exist in clinical practices worldwide, such as anemia management, phosphorus/calcium balance treatment regiments, and treatment characteristics, trajectories of patient parameters before death or hospitalization appear remarkably similar.


http://hemodialysis.com/the-monitoring-dialysis-outcomes-mondo-initiative/












The MONitoring Dialysis Outcomes (MONDO) initiative.Hemodialysis.com Interview with Dr.Len Usvyat PhDDirector, Integrated Care AnalyticsRenal Research InstituteFresenius Medical Care(cont)

• Hemodialysis.com: What should clinicians and patients take away from your report?Dr. Usvyat: We hope that our initiative can assist clinicians in understanding the dynamics of patient parameters over time on a global basis. As a result, this understanding can help improve patient outcomes. We hope that we can find certain clinical practices worldwide that are associated with better outcomes and thus can guide clinical decision making.

• Hemodialysis.com: What recommendations do you have for future research as a result of this study?Dr. Usvyat: We have a number of studies that we plan to undertake in the future; below is just a short list:

• body composition (by bioimpedance), nutrition and outcomes• anemia management• crp, nlr and albumin• sodium variability and outcomes• interdialytic weight gain and outcomes• seasonality• study of rare diseases (e.g. Anderson-Fabry disease; thrombotic microangiopathies)• study of pediatric and adolescent patients• We also welcome suggestions, recommendations, and thoughts from the nephrological community worldwide on potential

studies of interest.

• Citation:• The MONitoring Dialysis Outcomes (MONDO) initiative.• Usvyat LA, Haviv YS, Etter M, Kooman J, Marcelli D, Marelli C, Power A, Toffelmire T, Wang Y, Kotanko P.• Renal Research Institute, New York, NY 10128, USA

Blood Purif. 2013;35(1-3):37-48. doi: 10.1159/000345179. Epub 2013 Jan 22.








Decline in 20-year mortality after myocardial infarction in patients with chronic kidney disease: evolution from the prethrombolysis to the percutaneous coronaryHemodialysis.com Interview with Sjoerd T. Nauta MScThoraxcenter

, Department of CardiologyRotterdam 3015 CE, The NetherlandsSjoerd Nauta

• Hemodialysis.com: What are the main findings of the study?• Answer: We measured temporal trends in treatment and mortality after

myocardial infarction depending on kidney function at presentation in 12,087 patients admitted for myocardial infarction to a coronary care unit from 1985 to 2008. The patients were categorized into those with normal kidney function (estimated glomerular filtration rate over 90 ml/min per 1.73m2), and those with CKD as defined by Kidney Foundation practice guidelines, with 8632 patients (71%) at CKD stages 2–5. Treatment of MI improved in all groups of kidney function, but patients with stage 4–5 kidney dysfunction were less likely to receive evidence-based medical treatment and reperfusion therapy. Temporal trends in 30-day mortality reveal impressive mortality reductions during this 24-year period that were comparable for all stages of kidney function and were sustained during long-term follow-up. Although the outcome after MI improved across the whole range of kidney function, we showed that kidney dysfunction remains a strong risk factor for increased both short- and long-term mortality.



Decline in 20-year mortality after myocardial infarction in patients with chronic kidney disease: evolution from the prethrombolysis to the percutaneous coronary

Hemodialysis.com Interview with Sjoerd T. Nauta MScThoraxcenter, Department of CardiologyRotterdam 3015 CE, The NetherlandsSjoerd Nauta(cont)

• Hemodialysis.com: Were any of the findings unexpected?• Answer: No previous study has compared temporal improvement in treatment and

outcome according to different stages of kidney function for almost a quarter of a century. Therefore, beforehand it was difficult to predict the results of our temporal trend analyses. With these analyses we show that treatment of myocardial infarction improved in all groups of kidney function. We also showed that mortality reductions during this 24-year period were comparable for all stages of kidney function. In addition to the temporal trend analyses, our follow-up duration up to 20 years was unique.

• Hemodialysis.com: What should clinicians and patients take away from this study?• Answer: Our results are encouraging because we demonstrate a persistent temporal

increase in the use of cardioprotective therapies among all groups according to renal function during our 24-year study period. This provides evidence that improved clinical care in these patients is indeed possible. There can be little doubt that the increased use of cardioprotective therapies resulted in the observed mortality reduction. This observation should stimulate the use of evidence-based treatment in MI patients regardless of renal dysfunction.



Decline in 20-year mortality after myocardial infarction in patients with chronic kidney disease: evolution from the prethrombolysis to the percutaneous coronary

Hemodialysis.com Interview with Sjoerd T. Nauta MScThoraxcenter, Department of CardiologyRotterdam 3015 CE, The NetherlandsSjoerd Nauta(cont)


• Answer: Although we showed similar temporal trends for all stages of kidney function, the prognosis remains poor for patients with stage 4–5 CKD. Therefore, future research with the aim to improve treatment and prognosis in these patients will remain needed.

• Citation:• Decline in 20-year mortality after myocardial infarction in patients

with chronic kidney disease: evolution from the prethrombolysis to the percutaneous coronary

• Kidney Int. 2013 Mar 13. doi: 10.1038/ki.2013.71. [Epub ahead of print]• Nauta ST, van Domburg RT, Nuis RJ, Akkerhuis M, Deckers JW.• Thoraxcenter, Erasmus Medical Center, Rotterdam, The Netherlands.



Semaphorin 3A Is a New Early Diagnostic Biomarker of Experimental and Pediatric Acute Kidney InjuryHemodialysis.com Interview with Dr. Ganesan Ramesh, Ph.D.

Associate ProfessorDepartment of Medicine/Vascular Biology Center, CB-3702

Georgia Regents UniversityAugusta, GA 30912

• Dr. Ramesh, would you please explain the background and potential usefulness of Semaphorin 3A in Acute Kidney Injury?

• Acute kidney injury is a serious and frequent complication in hospitalized and ICU patients.• Currently used diagnostic test, serum creatinine is neither sensitive nor specific to detecting

AKI early. This poses a problem for clinicians to intervene early to prevent the kidney damage further. Our aim is to identify a sensitive biomarker that can be used to diagnose kidney injury early and accurately, in a non-invasive manner.

• In search for one such biomarker, we identified a protein called semaphorin 3A. Semaphorin 3A.

The Semaphorins make up the largest family of axon guidance cues yet described. Semaphorins are divided into 8 classes (classes 3-7 found in vertebrates). Class 3 Semaphorins are secreted, classes 4 through 6 are transmembrane proteins, and class 7 are membrane associated via glycosylphosphatidylinositol (GPI) linkage. They are characterized structurally by a conserved ~400 amino acid sema domain. They are classically described as collapsing factors and mediators of axon repulsion, although they may also act as context-dependent chemoattractants. Semaphorins have been shown to have roles in cardiovascular development and in the regulation of immune cell antigen presentation.



Semaphorin 3A Is a New Early Diagnostic Biomarker of Experimental and Pediatric Acute Kidney InjuryHemodialysis.com Interview with Dr. Ganesan Ramesh, Ph.D.

Associate ProfessorDepartment of Medicine/Vascular Biology Center, CB-3702

Georgia Regents UniversityAugusta, GA 30912

(cont)

• Initially we had characterized semaphorin 3A expression pattern and excretion in urine in a mouse model of AKI.Semaphorin 3A is expressed in distal tubules and collecting ducts and highly induced after ischemic and drug induced kidney injury.

• Urinary semaphorin 3A is elevated a few hours after ischemia reperfusion and highly correlated with development of AKI.• Therefore, we decided to test whether semaphorin 3A can be used as a diagnostic test for detecting AKI in human. In

collaboration with Dr. Prasad Devarajan, we measured semaphorin 3A in urine from pediatric patients who underwent cardiopulmonary bypass surgery.

• Our results suggest that semaphorin is an early and sensitive biomarker of AKI with high sensitivity and specificity of (over 90% accuracy). Our finding gives hopes to millions people around the world that kidney injury can be diagnosed early and intervention can begin to prevent kidney damage. We are pursuing additional studies in adult ICU patients and CKD patients to determine whether semaphorin 3A can be used as a diagnostic test to detect kidney injury early in other patient population as well. We are also developing antibodies to translate our finding to bench side.

• The manuscript describing semaphorin as biomarker of AKI is published in PLoS one http://dx.plos.org/10.1371/journal.pone.0058446).

• Citation:• Semaphorin 3A Is a New Early Diagnostic Biomarker of Experimental and Pediatric Acute Kidney Injury• Jayakumar C, Ranganathan P, Devarajan P, Krawczeski CD, Looney S, Ramesh G.• Department of Medicine and Vascular Biology Center, Georgia Health Sciences University, Augusta, Georgia, United States

of America.• PLoS One. 2013;8(3):e58446. doi: 10.1371/journal.pone.0058446.

Epub 2013 Mar 4.


http://dx.plos.org/10.1371/journal.pone.0058446

http://dx.plos.org/10.1371/journal.pone.0058446


Effect of donor age and cold storage time on outcome in recipients of kidneys donated after circulatory death in the UKHemodialysis.com Author Interview: Dr. Dominic Summers MBBChirDepartment of Surgery, School of Clinical Medicine

University of Cambridge, Cambridge, UK

• Hemodialysis.com: What are the main findings of the study?• Dr. Summers:• Firstly, we were able to confirm our (and others) previous work that showed that there

seems to be very little difference in survival and graft function of kidneys from donation after circulatory death (DCD) and kidneys from donation after brain death (DBD).

• Secondly, we were able to show that, while kidneys from older donors perform less well than kidneys from younger donors, there is no evidence that this is a particular problem for DCD donor kidneys.

• Finally, we showed that DCD donor kidneys are more susceptible to cold ischemic injury.Hemodialysis.com: Were any of the findings unexpected?

• Dr. Summers: There is a very widely held view, both in the UK and elsewhere, that DCD donor kidneys from older donors fare particularly poorly, and that we need to be much more selective with DCD donor kidneys than DBD donor kidneys.

• We showed that this was not the case. In addition, the fact that DCD donor kidneys are more susceptible to cold ischemic injury was thought likely, but had never been demonstrated before.


http://hemodialysis.com/effect-of-donor-age-and-cold-storage-time-on-outcome-in-recipients-of-kidneys-donated-after-circulatory-death-in-the-uk/






Effect of donor age and cold storage time on outcome in recipients of kidneys donated after circulatory death in the UKHemodialysis.com Author Interview: Dr. Dominic Summers MBBChirDepartment of Surgery, School of Clinical Medicine

University of Cambridge, Cambridge, UK(cont)

• Hemodialysis.com: What should clinicians and patients take away from your report?• Dr. Summers: This study provides more evidence and reassurance that kidneys from controlled DCD donors are a

valuable source of kidneys. This reassurance should mean that fewer DCD kidneys and potential donors are discarded and so more kidney transplants should take place.

• In addition, this has emphasized the need to transplant DCD donor kidneys quickly – this has already altered the national allocation policy in the UK, which has now been designed to minimize cold ischemia.

• Hemodialysis.com: What recommendations do you have for future research as a result of this study?• Dr. Summers: There is very large regional variation in the use of DCD donors in the UK and internationally.• It is important to understand the reasons for this, in order to increase overall donation rates. Further work that is of

interest is how to improve our ability to distinguish between ‘good’ and ‘bad’ kidneys for transplantation, to enable clinicians to make better choices for patients. This may include viability testing on ex-vivo rigs, better mathematical models, and the use of pre-implantation biopsies.

• Citation:• Effect of donor age and cold storage time on outcome in recipients of kidneys donated after circulatory death in the

UK: a cohort study.• Summers DM, Johnson RJ, Hudson A, Collett D, Watson CJ, Bradley JA.• Department of Surgery, School of Clinical Medicine, University of Cambridge, Cambridge, UK; Cambridge National

Institute for Health Research Biomedical Research Centre, Cambridge, UK; National Health Service Blood and Transplant, Bristol, UKLancet. 2012 Dec 19. pii: S0140-6736(12)61685-7doi: 10.1016/S0140-6736(12)61685-7. Epub ahead of print






http://www.ncbi.nlm.nih.gov/pubmed/23261146


Pharmacologic Therapy for Primary Restless Legs SyndromeHemodialysis.com Author Interview: Timothy J. Wilt, MD, MPHProfessor of Medicine and Core InvestigatorMinneapolis VA Center for Chronic Disease Outcomes Research

and the University of Minnesota School of Medicine Minneapolis, MN 55417

• Hemodialysis.com: What are the main findings of your study?• Dr. Fink: Our systematic review of randomized controlled trials

found that in patients with long-term Restless Legs Syndrome (RLS) that is at least moderately bothersome, treatment with certain medications (dopamine agonists [rotigotine, pramipexole, ropinorole] and calcium channel alpha-2-delta ligands [gabapentin enacarbil, pregabalin, or gabapentin]) can reduce RLS symptoms and improve sleep and quality of life at least in the short term.

• However, side effects including somnolence, nausea, skin application site reactions, worsening of symptoms (augmentation) and treatment withdrawals due to side effects are common.


http://hemodialysis.com/pharmacologic-therapy-for-primary-restless-legs-syndrome/










and the University of Minnesota School of Medicine Minneapolis, MN 55417(cont)

• Hemodialysis.com Were any of the findings unexpected?• Dr. Fink: We were surprised by the almost total lack of evidence directly comparing

different medications or comparing medications to nonpharmacologic therapies such as exercise, massage, hot baths etc.

• Furthermore, we were disappointed by the lack of information on the effectiveness and harms of treatments in pregnant women, young or old patients, those with milder symptoms or with other serious medical conditions including chronic kidney disease or undergoing dialysis. The latter is particularly important because RLS is common and bothersome in patients undergoing dialysis yet pharmacologic therapies may have different benefits and harms in these individuals.

• Until high quality studies are done we urge caution in extending our conclusions to these individuals. Additionally, we found no good scientific information on the effectiveness of other commonly used treatments including nonpharmacologic treatments as well as opioids or hypnotics that are not FDA approved for this indication and have the potential for abuse especially given the large placebo effect seen in the studies.












• Dr. Fink: Patients should inform their physician if they have bothersome sensations in their legs that includes distressing, irresistible urge to move them that is relieved by rest. This may be due to RLS but may be due to other conditions.

• An accurate diagnosis is important. Effective treatments for RLS are available and in patients with more severe symptoms may include medications. Physicians and patients now have up to date information on the effectiveness and harms of drug treatments for patients with at least moderately severe RLS symptoms in which to guide treatment choices. There are no high quality data on patients with less severe symptoms or and little information on nonpharmacologic therapies.

• The decision to initiate pharmaocologic treatment in patients with bothersome symptoms should be based on patient and provider assessment of the balance of these benefits and harms.












• Dr. Fink: Future randomized controlled and open label extension trials are needed to directly evaluate the long-term comparative effectiveness of different treatment approaches and in patients with milder symptoms and among younger or older patients or those with underlying comorbid conditions especially chronic kidney disease.

• Research is also needed to assess treatments commonly used but not evaluated including opioids, benzodiazepams and nonpharmacologic interventions.

• Citation: • Pharmacologic Therapy for Primary Restless Legs SyndromeA Systematic

Review and Meta-analysis• Wilt TJ, MacDonald R, Ouellette J, et al.

JAMA Intern Med. 2013;():1-10.doi:10.1001/jamainternmed.2013.3733.









Cost Analysis of Hemodialysis and Peritoneal Dialysis Access Costs in Incident Dialysis PatientsHemodialysis.com: Dr.Luis CoentrãoNephrology Research and Development UnitFaculty of Medicine, University of Porto & São João Hospital Centre

Alameda Professor Hernani Monteiro, Porto, 4202-451, Portugal

• Hemodialysis.com: What are the main findings of the study?• Dr. Coentrão: Both peritoneal catheters and arteriovenous

fistulae are safe and effective dialysis accesses for incident dialysis patients.

• Hemodialysis.com: Were any of the findings unexpected?• Dr. Coentrão: Peritoneal dialysis patients had fewer dialysis

access-related invasive procedures in comparison with hemodialysis patients with central venous catheters and fistulae.


http://hemodialysis.com/cost-analysis-of-hemodialysis-and-peritoneal-dialysis-access-costs-in-incident-dialysis-patients/















Cost Analysis of Hemodialysis and Peritoneal Dialysis Access Costs in Incident Dialysis PatientsHemodialysis.com: Dr.Luis CoentrãoNephrology Research and Development Unit

Faculty of Medicine, University of Porto & São João Hospital CentreAlameda Professor Hernani Monteiro, Porto, 4202-451, Portugal(cont)

• Hemodialysis.com: What should clinicians and patients take away from your report?• Dr. Coentrão: The peritoneal catheter should not be a barrier to the implementation

of a successfull peritoneal dialysis program.


• Dr. Coentrão:

• Prospective evaluation of dialysis access patency and complications in the long term.• Prospective evaluation of peritoneal and central venous catheters placed in CKD patients with

unplanned dialysis start.

• Citation:• Cost Analysis of Hemodialysis and Peritoneal Dialysis Access Costs in Incident Dialysis Patients• Luis A. Coentrao, Carla S. Araújo, Carlos A. Ribeiro, Claudia C. Dias, and Manuel J. Pestana• Perit Dial Int pdi.2011.00309;

published ahead of print March 1, 2013, doi:10.3747/pdi.2011.00309








A Self-Management Approach to Developing a Potassium Education ToolRachel Linzon, Josie Caruso-Ditta, Marla McKerracher, York Region Chronic Kidney Disease Program – Mackenzie Health, Richmond Hill, Ontario, Canada.

• The development of the Potassium Education Tool was a continuous quality improvement program initiative.

• Objective:• To incorporate a self-management approach in

developing a potassium education tool (PET) to improve patient’s ability to self-manage the potassium in their diet and improve serum potassium levels.


http://hemodialysis.com/self_management_approach_to_developing_a_potassium_education_tool/










(cont)

• Method:• In order to evaluate our original PET for potassium, 81 participants receiving hemodialysis responded to a pre-

test survey of open and closed-ended questions. These questions addressed ease of understanding, usefulness and readability.

• The responses from the closed-ended questions provided limited insight. It was the participant’s comments that provided the direction for the creation of a new PET. Participants requested that the information is:

• Alphabetized• Less cluttered• Larger font size• More cultural food choices• Specific quantities listed• Increased variety in fruits and vegetables

• The results influenced the development of a comprehensive PET booklet, which was piloted with a subgroup. Although the majority of the feedback was positive there was still a request for a single-page handout that could be taken to the grocery store, posted on the refrigerator and provide simplified guidelines to those requiring a low potassium diet.

• Subsequently, this booklet was adapted into a double-sided PET that was evaluated by a post-test survey.The final PET was distributed to all patients in the York Region Chronic Kidney Disease program.

• Effects of the double-sided PET were measured by comparing all patients’ serum potassium levels for 3 months with historical control.








(cont)

• Hemodialysis.com: What are the main findings of the study?• After developing a patient-centered tool, the format was adapted to meet patient needs and

incorporate adult learning principles. In the post-survey for the double-sided PET, participants reported:• More choices and variety• Less crowded• Easier to read• Specific portions and quantities identified• Results of the pre-test and post-test PET surveys were compared.

Ease of understanding improved from 94% pre-survey to 99% post-survey.• When comparing patients’ serum potassium, the averaged three-month results indicated a 24%

improvement (12.7% to 9.7%) in potassium for patients with a serum potassium level greater than 5.5mmol/L versus historical control.

• Hemodialysis.com: Were any of the findings unexpected?• Response: There were no unexpected findings.• Participants reported an increased independence in making food choices. The revised potassium tool

reinforced person-focused care and enabled patients to self-manage the potassium in their diet. This was evident in improved serum potassium levels.

• Patients enjoyed the self-management approach which included them in the process of creating education that impacts their daily lives.








(cont)

• Hemodialysis.com: What should clinicians and patients take away from this study?• Response: Incorporating self-management approaches to creating patient education

tools, empowers and encourages independence in patients requiring renal replacement therapy.

• As educators, Renal Dietitians should recognize a shifting trend in patient education from a traditional approach to a self-management approach.

• In the traditional approach, the Dietitian is the expert telling the patient what foods they can and cannot eat to control serum potassium levels. In the traditional approach, the overall goal is for the patient to comply to their low potassium diet in order to achieve a safe and normal serum potassium level. A typical PET depicts food columns specifying foods to choose or avoid. Often patients feel their diet lacks variety and are confused about portions.

• Whereas, a self-management approach to developing a PET would encourage patient feedback, establish a partnership with the Renal Dietitian which would empower them with the knowledge required to manage the potassium in their diet.








(cont)


• Response: Renal Dietitians should invite patients into the process of developing education tools and pilot the education with those who will use it. The feedback obtained in this process should be used to guide the development of education tools which will impact day-to-day lives of our patients.

• Citation:• This abstract was presented as a poster at the NKF

Conference in Gaylord Washington in May 2012For Informational Purposes Only. Not for Specific Medical Advice






Aldosterone and Mortality in Hemodialysis Patients: Role of Volume OverloadHemodialysis.com Author Interview: Dr. Der-Cherng Tarng, MD, PhDProfessor, Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital ,

and Department and Institute of Physiology, National Yang-Ming University, Taipei, Taiwan

• Hemodialysis.com: What are the main findings of the study?• Dr. Der-Cherng Tarng: Aldosterone level is inversely associated with

adverse outcomes in hemodialysis patients. Volume overload underlies this paradox. In the absence of volume overload, aldosterone is an independent risk factor for all-cause mortality and CV events in this population.

• Hemodialysis.com: Were any of the findings unexpected?• Dr. Der-Cherng Tarng: This study demonstrates an inverse association of

aldosterone levels with all-cause mortality and CV event rates in the presence of volume overload. This represents a paradoxical effect of volume status on mortality. In contrast, there was a significant, graded, and positive association of aldosterone levels with all-cause mortality and CV event rates in the 64% of participants without volume overload.


http://hemodialysis.com/aldosterone-and-mortality-in-hemodialysis-patients-role-of-volume-overload/%23more-361











Aldosterone and Mortality in Hemodialysis Patients: Role of Volume OverloadHemodialysis.com Author Interview: Dr. Der-Cherng Tarng, MD, PhD

Professor, Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, and Department and Institute of Physiology, National Yang-Ming University, Taipei, Taiwan(cont)

• Hemodialysis.com: What should clinicians and patients take away from your report?• Dr. Der-Cherng Tarng: Some ESRD patients with low aldosterone levels have a low risk of adverse

outcomes, as in the general population, whereas others have a high risk because they are in a state of volume overload, which lowers aldosterone levels and increases the risk of mortality and CV events.


• Dr. Der-Cherng Tarng: Our findings underline the importance of hyperaldosteronemia as a risk factor for adverse long-term outcomes among patients with ESRD, and of the masking of this association among individuals with volume overload.These findings support treatment of hyperaldosteronemia in hemodialysis patients who have achieved strict volume control.

• Hence, further research is warranted to clarify whether therapeutic interventions to mitigate volume overload and lower aldosterone concentrations may lead to improved outcomes in dialysis patients.

• Citation:Aldosterone and Mortality in Hemodialysis Patients: Role of Volume Overload.Hung S-C, Lin Y-P, Huang H-L, Pu H-F, Tarng D-C (2013)PLoS ONE 8(2): e57511. doi:10.1371/journal.pone.00







CMV seropositivity is associated with increased arterial stiffness in patients with CKDHemodialysis.com Author Interview: Charlie J. Ferro, BSc, MD, FRCPSchool of Immunity and Infection, University of BirminghamBirmingham, United Kingdom

• Hemodialysis.com:What are the main findings of the study?• Dr. Ferro: Patients with chronic kidney disease have an increased cardiovascular

risk that is not fully explained by traditional risk factors but appears to be related to increased arterial stiffness. Cytomegalovirus (CMV) infection is associated with increased cardiovascular risk although the mechanisms for this are unknown. In our study, arterial stiffness, as measured by carotid-femoral pulse wave velocity and arterial aortic distensibilty, was consistently and considerably higher in CMV seropositive patients.

• Hemodialysis.com: Were any of the findings unexpected?• Dr. Ferro: Although our hypothesis was correct, we were surprised by the

robustness and magnitude of the effect. For example, CMV seropositivity was associated with an average increase in pulse wave velocity of 0.7 m/s across quartiles of age. This figure has been an associated with a considerable increase in cardiovascular risk.


http://hemodialysis.com/cmv-seropositivity-is-associated-with-increased-arterial-stiffness-in-patients-with-ckd/









CMV seropositivity is associated with increased arterial stiffness in patients with CKDHemodialysis.com Author Interview: Charlie J. Ferro, BSc, MD, FRCPSchool of Immunity and Infection, University of BirminghamBirmingham, United Kingdom(cont)


• Dr. Ferro: Our results highlight the fact that previous CMV infection may not be as trivial as is currently considered in non-heavily immunosuppressed individuals with chronic kidney disease.


• Dr. Ferro: These findings have significant potential implications for the mechanism by which CMV infection might influence cardiovascular disease. How CMV affects the structure and/or function of large arteries requires further investigation.

• Ultimately, reducing the prevalence of CMV seropositivity might be a potential way of reducing the burden of cardiovascular disease in patients with chronic kidney disease, or indeed in the general population.









CMV seropositivity is associated with increased arterial stiffness in patients with CKDHemodialysis.com Author Interview: Charlie J. Ferro, BSc, MD, FRCPSchool of Immunity and Infection, University of BirminghamBirmingham, United Kingdom(cont)

• Citation:• Cytomegalovirus seropositivity is associated with increased

arterial stiffness in patients with chronic kidney disease.• Wall NA, Chue CD, Edwards NC, Pankhurst T, Harper L, Steeds

RP, Lauder S, Townend JN, Moss P, Ferro CJ.• School of Immunity and Infection, University of Birmingham,

Birmingham, United Kingdom ; Department of Nephrology, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom.PLoS One. 2013;8(2):e55686. doi: 10.1371/journal.pone.0055686.Epub 2013 Feb 25.









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Hemodialysis.com Kidney Disease Interviews March 24 2013

Health & Medicine

Transcript of Hemodialysis.com Kidney Disease Interviews March 24 2013