SHAGUN CHOPRA M.D.DIRECTOR OF DIALYSIS &TRANSPLANT NMCSD

ASSISTANT PROFESSOR OF MEDICINE UCSDASSISTANT PROFESSOR OF MEDICINE USUHS

Chronic Kidney DiseaseThe Recognized Epidemic

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?

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)..

ESRD prevalence counts and prevalence rates in the U.S. Graphic from USRDS 2010 Annual Report

Medicare expenditures on ESRD, not adjusted for inflation. Graphic from USRDS 2010 Annual Report

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?

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.

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*

CKD & CVD

DM, HTNAnemiaCoronary Calcification Cax Po4 <55Worsening HTNNephrotic syndromeHyperlipidemia

Management of CKD

Etiology of CKD/ProgressionAnemiaAccessAdequacyBPBone Mineral disorderCardiovascular RiskDiet/NutritionMedication Reconciliation

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.

Management of CKD

Etiology of CKD/ProgressionAnemiaAccessAdequacyBPBone Mineral disorderCardiovascular RiskDiet/NutritionMedication Reconciliation

TREAT

Management of CKD

Etiology of CKD/ProgressionAnemiaAccessAdequacyBPBone Mineral disorderCardiovascular RiskDiet/NutritionMedication Reconciliation

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

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

Management of CKD

Etiology of CKD/ProgressionAnemiaAccessAdequacyBPBone Mineral disorderCardiovascular RiskDiet/NutritionMedication Reconciliation

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.

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

Management of CKD

Etiology of CKD/ProgressionAnemiaAccessAdequacyBPBone Mineral disorderCardiovascular RiskDiet/NutritionMedication Reconciliation

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

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

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

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

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)

Management of CKD

Etiology of CKD/ProgressionAnemiaAccessAdequacyBPBone Mineral disorderCardiovascular RiskDiet/NutritionMedication Reconciliation

Diet

Protein RestrictionControversialTheory – High proteinhyperfiltration

increased glomerular hypertrophy glomerulosclerosis

Stage 4 slower progression on protein restriction.

Stage 5 though worried about malnutrition

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

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

Management of CKD

Etiology of CKD/ProgressionAnemiaAccessAdequacyBPBone Mineral disorderCardiovascular RiskDiet/NutritionMedication Reconciliation

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%

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.

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.

Source: SEARCH for Diabetes in Youth Study.NHW=Non-Hispanic whites; AA=African Americans; H=Hispanics; API=Asians/Pacific c Islanders; AI=American Indians