Assessment of Kidney function Assessment of Kidney function Challenges and opportunities George...
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Assessment of Kidney Assessment of Kidney functionfunction Challenges and
opportunities
George MoturiPhysician/Nephrologist
Aga Khan University Hospital Nairobi
25.04.2015
Road mapRoad map
• Introduction
• Why do you want to know the kidney function?
• Challenges: assessing kidney function in devolved HCS
• Opportunities: assessing kidney function in devolved in HCS
• Integrating e-medicine in assessing kidney function
• Conclusions
Road mapRoad map
• Introduction
• Why do you want to know the kidney function?
• Challenges in assessing kidney function in devolved HCS
• Opportunities in a assessing kidney function devolved in HCS
• Integrating e-medicine in assessing kidney function
• Conclusions
3. Secretion of erythropoitin 1,25-dihydroxy vitamin D3 (vitamin D activation) renin prostaglandin
Major Functions of the Kidneys
2. Excretion of metabolic products foreign substances (pesticides,
chemicals etc.) excess substance (water, etc)
1. Regulation of: body fluid osmolarity and volume electrolyte balance acid-base balance blood pressure
What is kidney disease?What is kidney disease?
• Acute kidney injury (AKI)Acute kidney injury (AKI)
• Acute kidney disease (AKD)Acute kidney disease (AKD)
• Chronic kidney disease (CKD)Chronic kidney disease (CKD)
• No kidney disease (NKD)No kidney disease (NKD)
Definition of CKDDefinition of CKD
Structural or functional abnormalities of the kidneys for >3 months ( ≤ 3 months), as manifested by either:
1. Kidney damage, with or without decreased GFR, as defined by
• pathologic abnormalities• markers of kidney damage
• urinary abnormalities (proteinuria)• blood abnormalities (renal tubular syndromes)• imaging abnormalities
• kidney transplantation2. GFR <60 ml/min/1.73 m2, with or without kidney
damage
NKF-K/DOQI
CKDCKDdeathdeathCKDCKDdeathdeath
ComplicationsComplicationsComplicationsComplications
Screening for CKD
risk factors:diabetes
hypertensionage >60
family historyUS ethnic minorities
CKD riskreduction;
Screening forCKD
Diagnosis& treatment;
Treat comorbid
conditions;Slow
progression
Estimateprogression;
Treatcomplications;
Prepare forreplacement
Replacementby dialysis
& transplant
NormalNormalNormalNormal IncreasedIncreasedriskrisk
IncreasedIncreasedriskrisk
KidneyKidneyfailurefailureKidneyKidneyfailurefailureDamageDamageDamageDamage GFRGFR GFRGFR
11.3 m11.3 m5.6%5.6%
7.7 m7.7 m7.7 m7.7 m3.8%3.8%
0.3 m0.3 m0.2%0.2%
Conceptual Model for CKD
Glomerular filtration rate does Glomerular filtration rate does not spell etiology of kidney not spell etiology of kidney
disease. disease. What does?What does?
•Urinalysis
•Urinary protein excretion
•Radiologic studies
•Kidney biopsy
The quagmire of The quagmire of kidney diseasekidney disease
Largely asymptomatic
Mitchell AJKD 2006
Road map
• Introduction
• Why do you want to know the kidney function?
• Challenges in assessing kidney function in devolved HCS
• Opportunities in a assessing kidney function devolved in HCS
• Integrating e-medicine in assessing kidney function
• Conclusions
Adjusted Hazard Ratio for Death from Any Cause, CardiovascularEvents, and Hospitalization among 1,120,295 Ambulatory Adults,
According to the Estimated GFR
Alan et al NEJM 2004
Road mapRoad map
• Introduction
• Why do you want to know the kidney function?
• Challenges: assessing kidney function in devolved HCS
• Opportunities in a assessing kidney function devolved in HCS
• Integrating e-medicine in assessing kidney function
• Conclusions
Glomerular filtration rate (GFR)Glomerular filtration rate (GFR)
The physiological mechanism of glomerular filtration is generally well understood
A more complex issue, however, is the measurement of GFR in clinical practice and especially the definition of “normal” renal function
Screening for CKD is not a Screening for CKD is not a preserve of the Nephrologistpreserve of the Nephrologist
The large number of patients who have CKD, together with the number of people at increased risk for it,
requires primary care providers, as well as specialists in areas other than nephrology, to increase their
familiarity with the use of GFR estimates
Assessing function - Assessing function - ToolsTools
• Urine output• GFR• Urinalysis• Novel biomarkers• Imaging • Biopsy
Production of creatinineProduction of creatinine
•Non-enzymatic breakdown product of phosphocreatine in muscle
•Produced at a relatively constant rate based on age, gender,race, and muscle mass
•Not affected by diet
Acute changes in kidney function are not immediately apparent.
Creatinine excretion is due not only to filtration (90%–95%) by the kidney but also to secretion (5%–10%) by the proximal tubule. If the patient with advanced CKD takes a substance that blocks tubular secretion of creatinine (eg, trimethoprim, cimetidine, cefoxitin), the serum creatinine level will increase abruptly, but the actual GFR will not change
Extra-renal elimination of creatinine occurs.
.
Other Limitations of Creatinine-Other Limitations of Creatinine-Based eGFRBased eGFR
Stevens NEJM. 2006
Cystatin CCystatin C
Produced by all nucleated cells at a constant rate and freely filtered at the glomeruli
Minimally affected by diet, gender, ethnicity, age and muscle mass
Affacted by glucocorticoids and thyroid hormone
Early detection of acute renal failure by serum cystatin C
Serum cystatin C is a useful detection markerof ARF, and may detect ARF one to two days earlier than creatinine.
Stefan et al. KI 2004:66:1115–1122
Creatinine Creatinine Equations Equations 1. Cockroft-Gault equation – 1973
2. Original MDRD Study equation - 1999 3. “Reexpressed” MDRD Study equation for standardized – 2005
4. CKD-EPI equation - 2009
Cystatin C Equations Cystatin C Equations
1. CKD –EPI cystatin C equation not adjusted for age, sex, and race
2. CKD – EPI cystatin C equation adjusted for age, sex, and race
3. CKD – EPI cystatin C and creatinine equation adjusted for age, sex, and race
Performance of Three Equations for Estimating Glomerular Filtration Rate (GFR)
Inker NEJM 2012
The combined creatinine–cystatin C equation performed better than equations based on either of these markers alone and may be useful as a confirmatory test for chronic kidney disease
Road map
• Introduction
• Why do you want to know the kidney function?
• Challenges in assessing kidney function in devolved HCS
• Opportunities: assessing kidney function in devolved HCS
• Integrating e-medicine in assessing kidney function
• Conclusions
Where do we start?Where do we start?
•National Vs regional kidney disease registries
•Standardized assessment of kidney function
•Referral pathways for kidney diseases
•Structured awareness campaigns
Measurement of Serum Measurement of Serum Creatinine – Current Status and Creatinine – Current Status and
Future GoalsFuture Goals• Creatinine measurement should be based on the isotope dilution-
mass spectrometry (IDMS) method
• Standardisation of serum creatinine measurements to IDMS
• Jaffe Assay (since 1886) – should be abandoned
Peake and Whiting Clin Biochem Rev 2006
Urine protein :Quantitative Urine protein :Quantitative measurementmeasurement
24 hour collection of urine for protein normal excretion is <150 mg/24 hour
Spot urine protein/urine creatinine ratio
Microalbuminuria: 30 – 300mg/24hrs
Macroalbuminuria: ≥ 300mg/24hrs
Screening for Urine proteinScreening for Urine protein
Dipstick: Gives green color, does not check for light chains
Negative– 10 mg/dlTrace – 15-25 mg/dl1-2+ – 30-100 mg/dl3+ – 300 mg/dl
Sulfosalicylic acid: white precipitate
Day-to-today clinical Day-to-today clinical situationssituations
Determining the exact GFR is rarely necessary. Instead, it is important to determine whether renal function is stable or getting worse or better—which can usually be accomplished by monitoring serum
creatinine value alone.
Road map
• Introduction
• Why do you want to know the kidney function?
• Challenges in assessing kidney function in devolved HCS
• Opportunities in a assessing kidney function devolved in HCS
• Integrating e-medicine in assessing kidney function
• Conclusions
Health in CloudHealth in Cloud
eHealth
• Fully integrated national health system – None in developing countries
mHealth
• WelTel SMS System• ChildCount+Register• Changamka(finance)
eTargets in Kidney diseaseseTargets in Kidney diseases
• Mobile updates
• Mobile reminders
• Mobile eGFR
Road map
• Introduction
• Why do you want to know the kidney function?
• Challenges in assessing kidney function in devolved HCS
• Opportunities in a assessing kidney function devolved in HCS
• Integrating e-medicine in assessing kidney function
• ConclusionsConclusions
Take away Take away MessagesMessages
• Often assessment of kidney function is the only indicator of renal impairment
• Structural defects can be present despite normal or even supra-normal kidney function
Take away Messages…
• Complete assessment kidney status will require GFR, Urinalysis, Imaging, +/- biopsy
• Reporting of renal function should be routine in all laboratories and if possible individualized
• We should and/or must assess kidney function of all our clients
• eHealth and mHealth can enhance kidney health in our population