Chronic Kidney Disease: Definitions and Optimal …

1 7/3/20081 Chronic Kidney disease : Definitions and Optimal ManagementJai Radhakrishnan, MD, MS, MRCP, FACC, FASNA ssoc Professor of Clinical MedicineColumbia University, New York, NY2 Objectives definition of CKD Prevalence and Scope of CKD Optimal management Delaying progression Treatment of Comorbidities Transition to End Stage Renal DiseaseKidney disease Outcomes Quality InitiativeK/ she have CKD?At what level of creatinine does a 65-year-old diabetic, hypertensive white woman weighing 50 kilograms have CKD? mg/dL4 Chronic >3 months Kidney Damage Hematuria/Albuminuria Biopsy Abnormal imaging tests Glomerular Filtration Rate<60ml/minDefinitions and Stages of Chronic Kidney Disease5 Good newsNO MORE 24-HOUR URINES!

2 Spot urines are of Proteinuria (positive dipstick):NormalAbnormal24 H Urine Protein< 300mg/24h>300mg/24hUrine SPOT protein/Creat. ratio (mg/gm)< 200mg/g>200mg/g7 Quantification of Proteinuria:(NegativeDipstick)Normal Micro -albuminuriaUrine AER( g/min)< 2020 - 200 Urine AER(mg/24h)< 3030 - 300 Spot albumin/Cr#ratio (mg/gm)< 3030 - 3008 Methods of Estimating GFR Inulin/iothalamate clearance GOLD STANDARD Creatinine Clearance (24 h urine) Equations base on serum creatinine Cockroft-Gault MDRD9 Modification of Diet in Renal disease Study Group. Ann Intern Med 130:461-470, 1999 MDRD equationfor predicting GFRMDRD not validated in: Diabetic Kidney disease serious comorbid conditions normal persons > 70 years ReplacementComplicationsEvidentComplicat ionsPossibleOther markers Kidney disease : proteinuria, hematuria, anatomicK/DOQI CKD StagingK/DOQI CKD StagingRequires 2 or more GFR, 3 or more months apartRequires 2 or more GFR, 3 or more months apart12 Does she have CKD?

3 At what level of creatinine does a 65-year-old diabetic, hypertensive white woman weighing 50 kilograms have CKD? mg/dL Creatinine = for GFR = 59 mL/ m213 Objectives definition of CKD Prevalence and Scope of CKD Optimal management Delaying progression Treatment of Comorbidities Transition to End Stage Renal Disease14 Incidence & Prevalence of ESRDUSRDS 1 (albuminuria)Stage 2 (GFR 60-89)Stage 3 (GFR 30-59)Stage 4 (GFR 15-29)Stage 5 (GFR <15 or ESRD)Number (in Millions)Prevalence of CKD: NHANES IIIC oresh Am J Kidney Dis. 2003 Jan;41(1):1-12.

4 16 Median age by race/ethnicity USRDS Hyper-Glomerulo- Secondary Interstitial Cystic/ Neoplasms/ Miscel-tension nephritis GN/ Vascu- Nephritis Hereditary/ Tumors laneouslitis Pyelo-CongenitalNephritisUSRDS 1999 Etiology of ESRD18 Objectives definition of CKD Prevalence and Scope of CKD Optimal management Delaying progression Treatment of Comorbidities Transition to End Stage Renal DiseaseKidney disease Outcomes Quality InitiativeK/ can be done to slow progression of renal disease ?Hypertension control ACE-Inhibitors/A2R-BlockersBlood sugar controlModerate protein restriction20 Early Aggressive Antihypertensive Treatment in Diabetic Nephropathy (n=10)Parving Lancet 1:1175-1179, 1983144/97128/84 AlbuminuriaGFR Declinemetoprolol, hydralazine, and furosemide or thiazide21 Meta Analysis: Lower Mean BP Results in Slower Rates of Decline in GFR in Diabetics and Non-Diabetics959598981011011041041071071 10110113113116116119119r =.

5 P< (mmHg)GFR (mL/min/year)130/85140/90 UntreatedHTN00--22--44--66--88--1010--1212--1414 Bakris GL, et al. Am J Kidney Dis. 2000;36(3) Pressure TargetsClinical StatusBP GoalHypertension(no diabetes or renal disease )<140/90 mmHg(JNC 7)Diabetes Mellitus<130/80 mmHg(ADA, JNC 7)Renal Diseasewith proteinuria >1 gram/24 hours, or diabetic Kidney disease <130/80 mmHg<125/75 mmHg(NKF)Chobanian AV et al. JAMA. 2003;289:2560 Diabetes Association. Diabetes Care. 2002;25:134 Kidney Foundatrion. Am J Kidn Dis. 2002;39(suppl 1):S1 S266. 23 SCORECARD:Awareness, Treatment and Control of Blood Pressure 1976-2000 (JNC-VII)010203040506070801976-19801988- 19911991-19941999-2000 AwarenessTreatmentControl24 Clinical Practice Guidelines for management of Hypertension in CKDType of Kidney DiseaseBlood Pressure Target (mm Hg)

6 Preferred Agents for CKD, with or without HypertensionOther Agentsto Reduce CVD Risk and Reach Blood Pressure TargetDiabetic Kidney DiseaseNondiabetic Kidney disease with Urine Total Protein-to-Creatinine Ratio 200 mg/gACE inhibitoror ARBD iuretic preferred, then BB or CCBN ondiabetic Kidney disease with Spot Urine Total Protein-to-Creatinine ratio <200 mg/gDiuretic preferred, then ACE inhibitor, ARB, BB or CCBK idney disease in Kidney Transplant RecipientCCB, diuretic, BB, ACE inhibitor, ARBNone preferred<130/8025 SCORECARD:ACE-I/ARB Use in Proteinuric Patients32%26%91%85%0%10%20%30%40%50%60% 70%80%90%100%19972005 DIABETESNO DIABETESMcClellan WM, et al.

7 Am J Kidney Dis. 1997 Mar;29:368-75 Nephrology Dialysis Transplantation 2005 20(6):1110-1115 . 26 Diabetes Control and Complications Trial 1441 patients with IDDM 726 without retinopathy at base line (the primary-prevention cohort) 715 with mild retinopathy (secondary-intervention cohort) Conventional (2 insulin injections/day vs Intensive (insulin pump or >3 insulin injections/day) mean F/U = yrsDCCT Research Group. N Engl J Med 1993;329:977-86. 27 Diabetes Control and Complications TrialPrevention of Microalbuminuria Microalbuminuria reduced by 39 percent (95 % 52 %)DCCT Research Group.)

8 N Engl J Med 1993;329:977-86. 28ukpdsUKPDS: MicroalbuminuriaUKPDS: MicroalbuminuriaUrine albumin >50 mg/L yearsSix yearsNine yearsTwelve yearsFifteen Risk& 99% CIFavoursconventionalFavoursintensive<29 ACCORD Glycemic Trial(Overarching trial)10,000 Age-eligible, high risk people with type 2 diabetes5,000 toIntensive Group(A1c Target < )5,000 toStandard Group(A1c Target )Treated and followedfor > 4 years (mean yrs)MAJOR CVD EVENTS30 ACCORD: Deaths in Intensive vsStandard Glycemic Control GroupsDeaths Standard GlycemicControlIntensive GlycemicControln203 (11/1000/y)257 (14/1000/y)Despite 10% lowering of primary outcome (MI rates) there was a 20% higher death and MortalitySalvador Dali - Premonition of Civil War32Go, A.

9 S. et al. N Engl J Med 2004;351:1296-1305Go NEJM, 351:1296-1305, 2004 Chronic Kidney disease and the Risks of Death, Cardiovascular Events, and 6045-59 30-44 15-29<15 Rate of Death From Any Cause*Rates of Death and Cardiovascular Events in Patients According to eGFRCV = cardiovascular. N = 1,120,295 adults. *Age-standardized rates per 100 person-years; CV event defined as hospitalization for coronary heart disease , heart failure, ischemic stroke, and peripheral arterial disease per 100 person-years. Go et al. N Engl J ;351 6045-59 30-44 15-29<15eGFR (mL/ m2) of CV Events 34 HOPE TRIAL:Predictive Variables for CV Death, MI, and StrokeVariableHazard > mg/dL JFE, et al.

10 Ann Intern Med. 2001;134(8) 2 (noproteinuria)Stage 2 (withproteinuria)Stage 3 Stage 4 PatientsDiscontinuedEvent freeRRTDiedCKD Patients Are More Likely to Die Than Progress to ESRDK eith D et al. Arch Int Med2004;164:659-663. RRT = renal replacement therapy36 Risk Factors for CVDTRADITIONAL Age Male gender Menopause Family history Hypertension Smoking Low HDL, high LDL Diabetes Inactivity, Obesity LVHNON TRADITIONAL CaxPO4 product Anemia Inflammation Hypoalbuminemia REVERSE EPIDEMIOLOGY Low cholesterol Low body weight Low blood pressure37 Malnutrition, Inflammation and Atherosclerosis (MIA syndrome) Stenvinkel P.