Chronic Kidney disease
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SHAGUN CHOPRA M.D.DIRECTOR OF DIALYSIS &TRANSPLANT NMCSD
ASSISTANT PROFESSOR OF MEDICINE UCSDASSISTANT PROFESSOR OF MEDICINE USUHS
Chronic Kidney DiseaseThe Recognized Epidemic
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Outline
ESRDWhat is CKD?Epidemiology of CKD?What does CKD predict?What can I do for my CKD patient?Where are we going with CKD?
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The number of individuals initiating treatment for end-stage renal disease (ESRD) in the United States, according to cause and calendar year, 1980 to 1999 (RenDER system of the United States Renal Data System (USRDS) (http://www.usrds.org)..
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ESRD prevalence counts and prevalence rates in the U.S. Graphic from USRDS 2010 Annual Report
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Medicare expenditures on ESRD, not adjusted for inflation. Graphic from USRDS 2010 Annual Report
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ESRD
Why is the life expectancy so poor?Why doesn’t a drug change survival in the
dialysis patient?Why is the CV risk so high?Is it too late?When should we start?
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Measurement of GFR
Inulin clearance- Gold standardCockroft-Gault: 1976. Measures CrClr. Studied
in 249 indiv. No AA. Overestimates due to secretion as well in edematous, hypoalbuminemic and nephrotic states
MDRD-1999. 1628 CKD patients. 6% DM. Underest if >60. Overestimates in malnourished, vegetarian diet and nephrotic states.
Cystatin C. made by nucleated cells. Altered by inflammatory states, leukocytosis, age, gender, diabetes etc. Not FDA approved.
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CKD Is Common: ~ 27 Million Americans Have CKD
*Prevalent dialysis patients.1. US Renal Data System. USRDS 2007 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States. 2007; 2. Coresh J, et al. JAMA. 2007;298:2038-2047; 3. Available at: http://www.kidney.org/news/newsroom/newsprint.cfm?id=51. Accessed April 18, 2008.
Stage of CKDStage of CKD GFR GFR (mL/min/1.73m(mL/min/1.73m22))
nn
11 90*90* 3,600,0003,600,000
22 60-89*60-89* 6,500,0006,500,000
33 30-59*30-59* 15,500,00015,500,000
44 15-29*15-29* 700,000700,000
55 < 15*< 15* 341,000*341,000*
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CKD & CVD
DM, HTNAnemiaCoronary Calcification Cax Po4 <55Worsening HTNNephrotic syndromeHyperlipidemia
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Management of CKD
Etiology of CKD/ProgressionAnemiaAccessAdequacyBPBone Mineral disorderCardiovascular RiskDiet/NutritionMedication Reconciliation
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Etiology/Progression
In the MDRD study Rate of Progression of CKD varies based on :
Underlying disease, proteinuria, Stage of CKD, comorbidities and treatments.
Retrospective analysis of MRFIT data showed that :1+proteinuria-3.1%, 2+ 15.7%, GFR 60-30 2.4%, GFR <30 41% over a 10 year period.
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Management of CKD
Etiology of CKD/ProgressionAnemiaAccessAdequacyBPBone Mineral disorderCardiovascular RiskDiet/NutritionMedication Reconciliation
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TREAT
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Management of CKD
Etiology of CKD/ProgressionAnemiaAccessAdequacyBPBone Mineral disorderCardiovascular RiskDiet/NutritionMedication Reconciliation
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Access
GFR <25ml/min or rapid progression consider placement of hemodialysis access.
Transplant referral at GFR<30 and placement on transplant list at <20.
AVFAVGTunneled CatheterPeriotenal dialysis
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Adequacy
Is the GFR adequate to avoid: volume overload, uremic sxs- nausea, malnutrition, pericarditis, lethargy, hyperk, acidosis. Most common reasons to start- malnutrition and volume overload.
?GFR<15ml/min per NKF are indications to consider the risks and benefits to initiating dialysis.
European Best Practice guidelines state GFR<6ml/min and consider at 8-10
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Management of CKD
Etiology of CKD/ProgressionAnemiaAccessAdequacyBPBone Mineral disorderCardiovascular RiskDiet/NutritionMedication Reconciliation
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Safety
NEJM 2006, Efficacy and Safety of Benazepril for advanced renal insuff
Benazepril vs placebo and both groups had BP<130/80. Both groups had 1.5gm proteinuria and GFR 25ml/min.
Benazepril reduced protenuria and lowered progression to ESRD and adverse events (hyperk) same.
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BP
MDRD trial subgroup evaluated aggressive BP lowering <125/75 vs <130/80: in 585 patients mean GFR<40ml/min
Decline in GFR was lowest in <1gm proteinuria but no benefit in aggressive BP arm
Patients with 1-3gm proteinuria had more rapid progression and a modest benefit from a lower BP
>3gm had the fastest rate of progression but a substantial benefit- 10.2 to 6.5ml/min per year.
Similar trends in another group with GRF<19ml/min
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Management of CKD
Etiology of CKD/ProgressionAnemiaAccessAdequacyBPBone Mineral disorderCardiovascular RiskDiet/NutritionMedication Reconciliation
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Progression to Renal Failure
NormalDiffuse
Nodular Hyperplasia
Adenomatous Hyperplasia
Early Nodular
VDR expression
CaSR expression
Partial 1,25(OH)2D resistance
1-Hydroxylase
Alteration of Parathyroid Gland Function
Progressive lossof kidney function
National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis. 2003;42(Suppl 3):S1-S201. Murayama A et al. Endocrinology. 1999;140:2224-2231. Satomura K et al. Kidney Int. 1988;34:712–716
CaSR=calcium sensing receptor
As hyperparathyroidism increases, the parathyroid gland becomes more and more resistant to vitamin D
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58
Block: Calcification and All-Cause Mortality in CKD Patients New to Dialysis
*CACS = Coronary artery calcification scoreaMultivariable adjusted (age, race, gender, diabetes). P value represents significance across all 3 groups.Adapted with permission from Block GA et al. Kidney Int. 2007;71(5):438-441.
Adjusted Survival by Baseline CAC
Scorea
0 6 12 18 24 30 36 42 48 54 60 66
0.00
0.25
0.50
0.75
1.00
Months
Su
rviv
al D
istr
ibu
tio
n F
un
ctio
n
P=0.002
CAC=0
CAC 1-400
CAC >400
(n=127)
N=127
A Preplanned Secondary Analysis of a Randomized Trial
in 127 Patients New to Hemodialysis
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59
Shantouf: Calcification and All-Cause Mortality in Maintenance Hemodialysis Patients
Adapted with permission from Shantouf RS, et al. Am J Nephrol. 2010;31(5):419-425.
Event rates increased from 11.1% to 41.7% as CAC increased across groups.
Eve
nt-
Fre
e S
urv
ival (%
)
0 12 24 36 48 60 72
Follow-up (months)
100
80
60
40
20
0
CAC 0CAC 1-100
CAC 101-400
CAC 400+
Event Rate: 11.1% (2/18)Event Rate: 18.7% (9/48)
Event Rate: 32.1% (9/28)
Event Rate: 41.7% (30/72)
A Cohort Study of 166 Maintenance Hemodialysis Patients
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PTH Testing: K/DOQI Guidelines
National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis. 2003;42(Suppl 3):S1-S201
CKD StageGFR
(mL/min/1.73m2)
3
4
5
30-59
15-29
<15 or dialysis
Every 12 months
Every 3 months
Every 3 months
Measurement of PTH
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PTH Goals: K/DOQI Guidelines
National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis. 2003;42(Suppl 3):S1-S201
CKD StageGFR
(mL/min/1.73m2)
3
4
5
30-59
15-29
<15 or dialysis
35-70
70-110
150-300
Target “intact” PTH(pg/mL)
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Management of CKD
Etiology of CKD/ProgressionAnemiaAccessAdequacyBPBone Mineral disorderCardiovascular RiskDiet/NutritionMedication Reconciliation
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Diet
Protein RestrictionControversialTheory – High proteinhyperfiltration
increased glomerular hypertrophy glomerulosclerosis
Stage 4 slower progression on protein restriction.
Stage 5 though worried about malnutrition
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Diet/Nutrition
Protein< 1.0 g/Kg in stage 4,5 of anmial protein
Sodium <2gm/dyMetabolic acidosis maintain >22Phosphorus <800mg/dyPotassium40-70meq/dyLipids- LDL<100Smoking Cessation
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Early Referral
Proteinuria, Stage 3 with proteinuria or rapid progression or unclear etiology of CKD, stage 4 and 5.
Multidisciplinary ApproachCV risk reductionPreparation for renal replacementPreemptive transplant
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Management of CKD
Etiology of CKD/ProgressionAnemiaAccessAdequacyBPBone Mineral disorderCardiovascular RiskDiet/NutritionMedication Reconciliation
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Percentage of the U.S. Population with 2 Risk Factors
Risk Factors=High BP, High Cholesterol, Diabetes,Risk Factors=High BP, High Cholesterol, Diabetes,†† Obesity, Obesity, SmokingSmoking
Risk Factors=High BP, High Cholesterol, Diabetes,Risk Factors=High BP, High Cholesterol, Diabetes,†† Obesity, Obesity, SmokingSmoking
19911991 20032003
30%
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Prevalence of hypertension in men according to age and race/ethnicity in the United States from the NHANES-III survey. Hypertension occurs earlier and more frequently in African-American men. Data from Burt, VL, Whelton, P, Roccella, EJ, et al, Hypertension 1995; 25:305.
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Prevalence of hypertension in women according to age and race/ethnicity in the United Statesr from the NHANES-III survey. Hypetension occurs earlier and more frequently in African-American women. Data from Burt, VL, Whelton, P, Roccella, EJ, et al, Hypertension 1995; 25:305.
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Source: SEARCH for Diabetes in Youth Study.NHW=Non-Hispanic whites; AA=African Americans; H=Hispanics; API=Asians/Pacific c Islanders; AI=American Indians
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