Diseases of the Kidney and Urinary System

Diseases of the Kidney and Urinary System DCPP(2) Chapter 36 John H. Dirks, Giuseppe Remuzzi, Susan Horton, Arrigo Schieppati, And S. Adibul Rizvi John Dirks, M.D. Toronto – April 20, 2006 Causes of diseases of the kidney and urinary system  Genetic Diseases  Glomerulonephritis  Infections, stones and obstructive uropathy  Benign prostatic hypertrophy  Acute renal failure  Diabetes  Hypertension Risk Factors for Kidney Disease 1 A. Risk factors susceptible to social and educational interventions  Low Birth weight  Smoking  Alcohol abuse  Illicit drug use  Analgesic abuse and exposure to toxic substances such as lead  Sedentary lifestyle THE NEGLECTED EPIDEMIC OF DEATHS FROM CHRONIC DISEASES IN DEVELOPING COUNTRIES 2005 15000 12000 Chronic diseases Communicable diseases Deaths (million) 9000 6000 3000 0 Low-income countries Lower-Middleincome countries High-income countries Fuster et al., Lancet, 2005 DEATH RATE FROM CHRONIC DISEASES IS EVEN HIGHER IN DEVELOPING COUNTRIES (2005) Death rate from chronic diseases (per 100,000) 1000 800 600 400 200 0 Nigeria Tanzania India Brazil China UK Canada Strong et al., Lancet, 2005 1,000,000 deaths Trends in Incidence and Prevalence of ESRD 700 Number of Patients (in thousands) 600 500 400 300 200 100 0 Number of Patients Projection 95% Confidence Interval 372,407 661,330 Point Prevalence R2=99.7% 326,217 86,825 98,953 172,667 Incidence R2=99.8% 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 2010 Year US Renal Data System. USRDS 2000 Annual Report. NIH, NIDDKD; Bethesda, MD: 2000. Number of patients worldwide treated with chronic dialysis from 1990 to 2010 2,500,000 1,490,000 426,000 1990 2000 2010 Lysaght, J Am Soc Nephrol, 2002 Mild renal dysfunction is (Albuminuria and slight decrease in GFR) is highly prevalent Stage Description Albuminuria, normal or  GFR Albuminuria, mild  GFR Moderate  GFR Severe  GFR Kidney Failure GFR (ml/min/1/73 m2) Est. Prevalence USA 3.3% 3.0% 4.3% 0.2% 0.2% Est. Prevalence GRONINGEN 1.3% 3.8% 5.3% 0.1% 0.0% 1 2 3 4 5 > 90 60 - 89 30 - 59 15 - 29 < 15 or RRT Total K/DOQI Clinical Practical Guidelines Am J Kidney Dis 2003 11.0% 10.5% Coresh et al; Am J Kidney Dis 2004 De Zeeuw et al; Kidney Int 2005 ESTIMATED CHRONIC KIDNEY DISEASE in URUGUAY According NANHES III distribution and the Uruguayan ESRD prevalence Population over 20 years old : 2.386.032 NANHES III % of Population Uruguay % of Population Uruguay CKD Population Stage 1 Stage 2 Stage 3 Stage 4 Stage 5 total 3,3 3,0 4,3 0,2 0,2 11,0 2,0 1,8 2,6 0,12 0,12 6,7 47.783 43.521 62.380 2.900 2.900 159.576 At risk population: NHANES III 1988-1994: National Kidney Foundation CKD guidelines Stage 5 n=300,000 Stage 4 n=400,000 Stage 3 n=7,600,000 Stage 2 n=5,300,000 Stage 1 n=5,900,000 Clinical Practice Guidelines for CKD AJKD 2002 Projection in the 2025 High blood pressure/chronic renal disease Diabetes Need of dialysis 300 millions 30 millions 8 millions CHINA TYPE 2 DIABETES MELLITUS IS A PUBLIC HEALTH CONCERN People with diabetes: (2004-2030) 30.7 33.8 52.4 42.3 18.6 80.9 16.7 71% 127% 102% 22.8 28.3 9.1 32.9 211% 255% 18.2 2000 81% 0.9 1.6 78% 2030 * In million subjects World 2000 2030 154 m 370 m Developed 55 m 84 m Developing 99 m 286 m WHO, March 2003 THE FACT 40 % of type 1 and of type 2 diabetics are at risk of overt nephropathy PROGRESSION OF NEPHROPATHY IN TYPE 2 DIABETES Normoalbuminuria UAE µg/min < 20 0 Micro 20 - 200 15 Macro > 200 ESRD 10 25 Duration of diabetes (years) Age-and sex-adjusted deaths 150 (x 1000 person-year) 125 100 75 50 25 0 Healthy subjects Non proteinuric Proteinuric diabetics diabetics CHRONIC KIDNEY DISEASE PREDICTS CARDIOVASCULAR EVENTS 1,120,295 adults from the Kaiser Permanent Renal Registry of Northern California Median follow-up: 2.84 years Age-standardized rate of cardiovascular events 40 (per 100 person-yr) 63 30 21 20 11 10 2 3 0 > 60 45-59 30-44 15-29 < 15 Estimated GFR (ml/min) Go et al., N Engl J Med, 2004 PATIENTS WITH A DIAGNOSIS OF CKD (WITH OR WITHOUT DIABETES) ARE 5 TO 10 TIMES MORE LIKELY TO DIE FROM CVD THAN TO REACH ESRD General Medicare enrollees (1996-2000) in U.S. Approximately 1.1. million individuals for each year assessed Follow-up: 2 years 50 Death ESRD Percent of patients 40 30 20 10 0 No DM/ No CKD DM/ No CKD No DM/ CKD DM/ CKD Collins et al., Kidney Int, 2003 CAPTOPRIL STUDY: ACE-I IS MORE RENOPROTECTIVE CONVENTIONAL THERAPY IN DIABETIC RENAL DISEASE Doubling of baseline creatinine (%) 0 THAN Captopril 25 50 75 Conventional therapy 100 Baseline creatinine > 1.5 mg/dl 0 1 2 3 4 Lewis et al. N Engl J Med, 1993 Time (years) PRIME; Early and Late intervention with Renin-angiotensin-system intervention (AIIA) are cost saving in type 2 diabetes Cumulative costs per patient (€) 45,000 Placebo + Conventional Tx Late AIIA (Irbesartan) 25,000 35,000 15,000 Early AIIA (Irbesartan) 5,000 0 0 2 4 6 8 10 12 14 16 18 20 22 24 Years since baseline age of 58 Palmer et al; Diabetes Care 2004 INCREASING ACE INHIBITOR USE WITH FULL MEDICARE COVERAGE EXTEND QUALITY-ADJUSTED LIFE-YEARS (QALYS) Increased QALYs per beneficiary 0.70 0.60 0.50 0.40 0.30 0.20 0.10 0 40 50 60 70 80 90 100 Overall ACE inhibitor use (%) * Compared with current practice (no coverage) Rosen et al., Ann Int Med, 2005 Common and Novel Risk factors for Cardiovascular and Renal Disease progression Age Gender Body Weight Smoking Blood pressure Cholesterol Diabetes CRP, pro-BNP etc Hemoglobin GFR Albuminuria! the Framingham Risk Score Wilson PWF et al. Circulation 1998; 97: 1837-47 Novel Risk markers or FACTORS? de Zeeuw; Oct 2004 U.S. KIDNEY FAILURE ENDING A 20-YEAR CLIMB RATES STABILIZE Since 1999 average annual increase has been < 1%, compared to an average 5% in the previous decade Incident ESRD patients* (per million population) 400 300 200 100 0 80 82 84 86 88 90 92 94 96 98 00 02 04 * Adjusted for age, gender, race USRDS, 2005 DECLINING INCIDENCE OF ESRD IN DENMARK 1990-2004 160 140 120 Incidence of all ESRD (PMP) 100 80 60 Incidence 40 of DM-ESRD (PMP) 20 0 1990 1995 2000 2001 2002 2003 2004 Sorensen et al, Abstract, ASN, 2005. Cost-effectiveness of Selected Interventions for Kidney Disease Intervention Center Hemodialysis Alternative No RRT Outcome (2000US$) 55,000 – 80.000 life/year 79,000 – 114,000/QALY 33,000 - 50,000 life/year 47,000 - 71,000/QALY Home Hemodialysis Kidney Transplant ACE inhibitors for all Type I diabetics with macroproteinuria Screening diabetic relatives of nephropathy patients Treat all Type II diabetics with ACE inhibitors Treat all insulin dependent No RRT No RRT 10,000 life/year 11,000/QALY 1,100/QALY Screening potentially cost saving No RRT No screening Screening for microalbuminuria & treating positives Screening & treating those positive for Incremental cost effectiveness ratio is 7500/QALY Treating all Type I’s dominates under plausible range of 2006-2015 EXPECTED DEATHS AVERTED DUE CARDIOVASCULAR DISEASE AND DIABETES 15.0 15 TO Deaths averted (million) 10 5 3.1 0 Low-middle income countries High income countries Most of the benefit will be for emerging countries Strong et al., Lancet, 2005 Guidelines for diseases of the kidney and urinary system in developing countries 1. Expanded surveillance and more epidemiological studies on prevalence, including establishment of an international kidney disease data centre 2. Promote awareness of early symptoms and knowledge of prevention measures 3. Develop kidney disease programs in context of diabetes and hypertension with primary and secondary prevention measures to reduce ESRD Guidelines (cont’d) 4. Develop practices for dealing with ARF for children with diarrheal disease, and when arising from major emergencies such as earthquakes 5. Use international bodies to advise regional & national health organizations on kidney and urological disease 6. Develop educational programs through existing agencies to provide update training for all levels of health care personnel 7. Develop 10 internationally funded centres of excellence for research, education, clinical care and prevention in the developing world over the next decade Risk Factors for Kidney Disease 2 B. Risk factors susceptible to pharmacological interventions  Hypertension  Dyslipidemia  Poor glycemic control in diabetic patients  Proteinuria C. Biological Markers  Hemoglobin  Insulin-resistant syndrome  Proteinuria  Serum creatinine