Chronic Kidney Disease

Chronic Kidney Disease Chronic Kidney Disease (CKD) Educational Objectives Outline Demographics Propose Strategies to slow progression and improve outcomes Plan for treatment of CKD Chronic Kidney Disease Definition Kidney damage for 3 months Structural or functional abnormalities with or without decreased GFR Pathological abnormalities Abnormal blood or urine tests Abnormal imaging GFR <60 ml/min/1.73m2 for 3 months K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification. NKF 2002 1

Stages of CKD Stage Description GFR (ml/min/1.73 m 2 1 Kidney damage with normal or GFR 2 Kidney damage with mild GFR 90 60-89 3 Moderate GFR 30-59 4 Severe GFR 15-29 5 Kidney Failure < 15 (or dialysis) The Five Stages of CKD Stage 1 2 3 4 5 Kidney Damage with Normal or GFR Kidney Damage With Mild GFR Moderate GFR Severe GFR Kidney Failure 90 60-89 30-59 15-29 <15 or dialysis GFR (ml/min/1.73m 2 ) Prevalence of CKD CKD affected an estimated 16.8% of adults aged >20 years during 1999--2004, an increase from the recalculated NHANES III (1988-- 1994) estimate of 14.5%. Persons with CKD have high rates of morbidity, mortality, and health-care utilization). The findings in this report suggest that CKD is a growing health problem in the United States. CKD prevalence was greater among older persons and among persons with diabetes, cardiovascular disease, and hypertension than among persons without these conditions, supporting previous findings. Mexican Americans and non-hispanic blacks had greater prevalence of CKD than non-hispanic whites. The large disparity in prevalence among those with stage 1 CKD might be explained, in part, by racial/ethnic differences in microalbuminuria among non- Hispanic blacks and Mexican Americans. 2

Prevalence of CKD Stage GFR (ml/min/1.73 m 2 ) Prevalence (Millions of Patients) 1 90 5.9 2 60 89 5.3 3 30 59 7.6 4 15 29.4 5 < 15 (or dialysis).3 The Challenge of Kidney Disease Primary-care physicians have a pivotal role in early detection and treatment of CKD. Common condition usually asymptomatic ~ 8.3 million people have GFR <60ml/min/1.73m 2 Increasing prevalence Aging, diabetic, obese, and minority populations Expensive ESRD projected to cost Medicare $28 billion in 2010 7% of budget for 0.6% of population Jones. Am J Kidney Dis. 1998;32:992. Pereira. Kidney Int. 2000;57:351. US Renal Data System. USRDS 2000 Annual Report. NIH, June 2000. Projected Growth in CKD Stage 5 Prevalence 3.0 Number of patients (millions) 2.0 1.0 0 1978 0.7 million 1.3 million 2000 2010 2020 2030 Year 2.2 million (60% diabetic) Gilbertson D et al. Presented at the 2003 ASN annual meeting. Available from: http://www.usrds.org/2003/pres/html/5u_asn_projections_files/frame.htm 3

Prevalence of ESRD Total ESRD Dialysis Transplant 500,000 Patients 400,000 300,000 200,000 100,000 0 1978 1980 1982 1984 1986 1988 1990 Year 1992 1994 1996 1998 2000 USRDS 2003 Annual Data Report. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2003. Kidney Failure Is a Rapidly Growing Problem 700 661,330 600 Number of Patients (in thousands) 500 400 300 200 372,407 172,667 Prevalence 100 0 98,953 Incidence 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 2010 Adapted from: US Renal Data System 2000 Annual Data Report. ESRD Incident Rates Adjusted by Age & Race/Ethnicity 2006 ADR USRDS 4

Prevalence of End Stage Kidney Disease Primary Diagnosis for Patients Who Start Dialysis Other 13.4 % Cystic Kidney 2.3% Unknown 4.0% Glomerulonephritis 8.3% Diabetes 44.8% Hypertension 27.2% Adapted from: US Renal Data System 2004 Annual Data Report. Incidence and Prevalence Dialysis and Transplant Patients 2006 ADR USRDS Incidence and Prevalence Modality of ESRD Care Adjusted for Age, Gender and Race 2006 USRDS 5

Medicare Population--2004 Distribution of CKD, HTN, & Diabetes 2006 ADR USRDS Medicare Population--2004 Distribution of Costs CKD, HTN, & Diabetes 2006 ADR USRDS Adjusted ESRD Incident Rates Primary Diagnosis 2006 ADR USRDS 6

Incidence Rates of Kidney Failure Diabetes as Primary Diagnosis Unadjusted / Million Population 1990 2000 205+ (260) 125 to <205 57 to <125 49 to <57 Below 49 (44) 205+ (245) 125 to <205 57 to <125 49 to <57 Below 49 (NA) Adjusted ESRD Incident Rates for Diabetes Adjusted for Age, Gender and Race The Risk of Kidney Failure Due to Diabetes 700 White Black Native American Asian Hispanic All Rate per Million Population 600 500 400 300 200 100 0 1992 1993 1994 1995 1996 1997 1998 1999 2000 Year Adapted from: US Renal Data System 2002 Annual Data Report. 7

Life Expectancy US Dialysis Patients 15 10 Years 5 0 29 34 39 44 49 54 59 64 69 74 20-24 25-30- 35-40- 45-50- 55-60- 65-70- 75-79 80-85+ 84 Age USRDS 1998. Annual Data Report. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 1998. Cause of Death in the US in 2000 Kidney Failure vs. Cancer Deaths (in Thousands) 157 99 57 42 32 Lung Cancer Kidney Failure Colon Cancer Breast Cancer Prostate Cancer Miniño AM, et al. Natl Vital Stat Rep. 2002;50:1-119. Risk Factors for CKD Diabetes Hypertension Older age Family history of kidney disease or diabetes Male gender Racial/Ethnic Background: African American Native American Asian-American Pacific Islander Latin American Tobacco Use 8

Risk Factors for CKD Progression Poorly controlled DM Poorly controlled BP Anemia Hyperlipidemia High-protein diet Atherosclerosis Obesity Exposure to nephrotoxic drugs NSAIDS Contrast dye McCarthy. Mayo Clin Proc. 1999;74(3):269. 35 Current CKD Outcomes Are Poor Annual Likelihood of Event 30 25 20 15 10 5 0 <65 65+ N=40,250 D ND D ND Death ESRD D=diabetes; ESRD=end-stage renal disease; ND=no diabetes. Adapted from US Renal Data System 2002 Annual Data Report. Medicare costs are 2.7 times greater for CKD patients than for non-ckd patients Annual Medicare Cost Per Patient ($) $70,000 $60,000 $50,000 $40,000 $30,000 $20,000 $10,000 $0 $62,676 $16,476 $6,060 Non-CKD CKD Dialysis Based on data from USRDS 2002; costs based on diagnostic codes obtained from billing data; patients> 67 years of age Hunsicker LG. J Am Soc Nephrol. 2004;15:1363-1374 9

Increase in CKD Population Leads to Predicted Shortage of Nephrologists 7.6 million people with egfr 30-60 ml/min/1.73 m 2 (Stage 3 CKD) 1 4500 estimated full-time nephrologists 2 The Stage 3 CKD population would contribute to 2000 new patients per nephrologist 2 7 new patients per day per nephrologist 2 1 National Kidney Foundation. Am J Kidney Dis. 2002;39(2 suppl 1):S1-S266. 2 Suki WN. Am J Kidney Dis. 1999;33:796-797. Recommended Screening Tests for Patients at Risk for CKD Screening is the beginning of a complex management process for CKD. Serum creatinine Blood pressure Glucose Urinalysis Microalbuminuria/proteinuria McCarthy. Mayo Clin Proc. 1999;74:269. American Diabetes Association. Diabetes Care. 2000;23(suppl 1):32. Measure Renal Function Serum Creatinine and BUN are not Sufficient 24 hour creatinine clearance Cockroft-Gault estimation MDRD equation (Levey modification) Measure microalbuminuria 10

Cockroft-Gault Equation (140-age) x Body Mass in Kg Cl Cr = 72 x Scr 85 % for Women Renal Function and Age ClCr = (140 - Age) x Lean Body Mass 72 x Serum Creatinine 120 ml/min = (140-20) x 72 kg 72 x 1.0 mg/dl 60 ml/min = (140-80) x 72 kg 72 x 1.0 mg/dl Probability of Serum Creatinine Measurement 2004 2006 ADR USRDS 11

Geographic Variation in the Probability of Serum Creatinine Measurement 2004 2006 ADR USRDS Probability of Urine Protein Measurement 2004 2006 ADR USRDS CKD MODEL 12

CREATININE AND GFR Complications Associated with CKD Diabetes: CKD progression and CV disease Hypertension: CKD and CV disease Dyslipidemia: CKD progression and CV disease Anemia: CKD progression and CV disease Cardiovascular disease and mortality Osteodystrophy Malnutrition Metabolic Acidosis Delayed Detection of CKD Leads to Under Use of Interventions Lack of interventions Hypertension Anemia Cardiovascular Disease Diabetes Malnutrition Delayed consultations Nephrologists Cardiovascular Specialists Dietitians Lack of patient education Temporary catheters at initiation of dialysis 13

Interventions Slow CKD Progression and Decrease Cardiovascular Risk Treatment of Hypertension Diabetes Anemia Hyperlipidemia Hypertension and CKD CKD Hypertension Zabetakis. Am J Kidney Dis. 2000;36(suppl 3):S31. Classification of Hypertension in Adults Classification Blood Pressure Normal < 120/< 80 Pre-Hypertension 120-139 80-89 Stage 1 Hypertension Stage 2 Hypertension 140-159 90-99 160 100 Chobanian, et al. JNC 7. JAMA 289:2560-2572, May 21, 2003 14

Blood Pressure Is Poorly Controlled in CKD <130/85 mm Hg 11% 140/90 62% 27% <140/90 Coresh. Arch Intern Med. 2001;161:1207. Hypertension and CKD BP <130/80 for CKD or proteinuria Most patients 3 or more drugs to achieve goal Start with 2 drugs if >150/90 ACEI or ARB in diabetics Thiazide or loop diuretic Other appropriate drugs Chobanian, et al. JNC 7. JAMA 289:2560-2572, May 21, 2003 Blood Pressure Control Choice of agents ACE inhibitors Angiotensin-receptor blockers (ARBs) Calcium channel blockers (CCBs) Diuretics Low-sodium diet Combination therapy Del Vecchio. J Nephrol. 2001;14:7. JNC VI. Arch Intern Med. 1997;157:2413. 15

Diabetic Nephropathy Sixteen Million Diabetics in U.S. 1.4 million new cases each year > 3,800 each day Most Frequent Cause of Renal Failure 30 % - 40 % of Type I 10 % - 20 % of Type II Division of Diabetes Translation National Center for Chronic Disease Prevention and Health Promotion Centers for Disease Control and Prevention United Kingdom Prospective Diabetes Study Group (UKPDS) Design Multicenter Randomized Controlled Trial 5,100 patients Glucose control Hypertension control UKPDS. BMJ. 1998;317:703-713. United Kingdom Prospective Diabetes Study Group (Hypertension Study) Objectives: Compare Risk Tight B.P. control Less tight control Protocol 1148 hypertensive patients with Type II DM mean age: 56 years ACEI or beta blocker 758 randomized to tight control 390 to less tight control Follow-up: 8.4 years UKPDS. BMJ. 1998;317:703-713. 16

Blood Pressure Achievement (UKPDS) 160/94 mm Hg Tight 144/82 mm Hg Less Tight 154/87 mm Hg Difference = 10/5 mm Hg UKPDS. BMJ. 1998;317:703-713. Comparative Effects of Tight Glucose Control Versus Tight Blood Pressure Control (UKPDS) 0 Stroke Any DM Endpoint DM Death Microvascular Complications -10 Percent -20 Reduction in Risk -30 * -40-50 * *P<0.05 * * Tight Glucose Control Tight BP Control UKPDS. BMJ. 1998;317:703-713. The Effect of Angiotensin-Converting-Enzyme Inhibition on Diabetic Nephropathy 409 IDDM Patients Randomized Proteinuria more than 500 mg/day Creatinine less than 2.5 mg/dl 3-4 years follow-up Captopril 25 mg tid or placebo Blood pressure equally controlled Doubling of serum creatinine Lewis EJ, Hunsicker LG, Bain RP, et al. N Engl J Med 1993;329:1456-1462 17

% With Doubling of Base-line Creati 80 70 60 50 40 30 20 10 0 0 1 2 3 4 5 Years of Follow-up Placebo >= 1.5 mg/dl Captopril >= 1.5 mg/dl Placebo < 1.5 mg/dl Captopril < 1.5 mg/dl Lewis, et al. NEJM 329:1456-62, 1993. RENAAL Reduction of Endpoints in Non-insulin Dependent Diabetes Mellitus With the Angiotensin II Antagonist Losartan Multicenter Placebo controlled 1,513 type II diabetics 3.4 years Stopped 13 months early Randomized Brenner et al. NEJM Sept. 2001 RENAAL Risk Reduction 0-5 -10 Percent -15-20 -25-25 -25-30 -35-35 Proteinuria Doubling of Serum Creatinine ESRD Brenner et al. NEJM Sept. 2001 18

Preventing Progressive Diabetic Nephropathy ACEI +/or ARB Microalbuminuria Proteinuria Hypertension Monitor Albumin Excretion Creatinine Potassium ACEI +/or ARB ADA Guidelines Type 1 with proteinuria ACEI delay progression of nephropathy Type 2 with microalbuminuria ACEI and ARB delay progression to proteinuria Type 2 with hypertension, proteinuria, and Scr > 1.5 mg/dl) ARB have been shown to delay the progression of nephropathy. Diabetes Care 26:S94-S98, 2003 ACE Inhibitors Recommended for Slowing the Progression of CKD Compelling Indication: Unless contraindicated, patients with hypertension who have renal insufficiency should receive an ACE inhibitor and/or ARB to control hypertension and to slow progressive renal failure. JNC VII. NHLBI. 19

Screening for Microalbuminuria All Diabetics Screen Annually Dip Stick 24 - Hour Collection Albumin:Creatinine Ratio Titrate drugs and follow Planning for Patients with CKD Stage 1 CKD GFR > 90 ml/min Establish diagnosis Initiate treatment for underlying kidney disease Develop strategies to slow progression Aggressive BP control Tight glucose control Lipid management ACEI or ARB Treat co-morbidities Aggressive approach to CVD risk reduction Planning for Patients with CKD Stage 2 CKD GFR 60-89 ml/min Continue Stage 1 strategies Estimate rate of progression of CKD Discuss treatment options for RRT Preserve Access Sites Inform patient not to allow venipuncture in non-dominant arm Avoid central lines No PICC lines 20

Planning for Patients with CKD Stage 3 CKD GFR 30-59 ml/min Continue Stage 1 and 2 strategies Evaluate and treat complications Anemia Acidosis Metabolic bone disease Begin vascular access planning in late Stage 3 patients Planning for Patients with CKD Stage 4 CKD GFR 15-29 ml/min Prepare for RRT Establish vascular access Refer for transplant evaluation as GFR approaches 20 ml/min Benefits of Timely Placement of Vascular Access Increased prevalence of fistulae Increased maturation of fistulae Better incorporation of PTFE grafts Obviates need for temporary access Costs Discomfort Venous stenosis Infection 21

CKD Clinical Action Plan Stage GFR Action 1 90 Dx and Rx Rx co-morbidities Slow progression CVD risk reduction 2 60-89 Estimate progression Discuss Rx options Preserve Access Rx Co-morbidities 3 30-59 Evaluate and treat complications 4 15-29 Preparation for RRT Establish vascular access 5 < 15 (or dialysis) Initiate RRT Optimal CKD Patient Care Early Detection of CKD Delay progression Prevent complications Treat co-morbidities Prepare for RRT ACEi or ARB Anemia Cardiac disease Educate patient BP control Malnutrition Vascular disease Select RRT modality Blood sugar control Osteodystrophy Diabetes Create access Protein restriction? Acidosis Initiate dialysis in a timely fashion Adapted from Pereira BJ. Kidney Int. 2000;57:351-365. Team Approach: Role of PCP and Nephrologist in CKD PCP Screen and identify risk factors of CKD, including: Diabetes CVD Anemia Provide ongoing management of patients with CKD Provide role-specific patient education Nephrologist Assist in development of care strategy Aid recommendation and implementation of patient care Provide role-specific patient education 22

Kidney Care Recommendations GFR ml/min/1.73m 2 Normal( 90) 80-60- 40-30- PCP Primary Care Degree of interaction Specific Indication At-risk screening and intervention Progression Prevention Patient Education Nephrologist Consultation Referral interval As needed Q 1-2 Years Q 6 Months 20-10- 0- Access Placement RRT Renal Replacement Therapy (RRT) Q 1-3 Months As required Adapted with permission from Bolton WK, Owen WF. Postgrad Med. 2002;111:97-108. Benefits of Early Intervention in the Management of CKD Improved teamwork between physicians Decreased risk of cardiovascular complications Delayed progression of CKD Improved dialysis outcomes Better educated and prepared patients Pereira. Kidney Int. 20 Benefits of Timely Nephrology Referral Informed selection of dialysis modality Timely placement of vascular access Timely initiation of dialysis Less frequent and shorter hospitalizations Potentially less mortality Lower incidence of anemia and malnutrition 23