3. Lysaght, J Am Soc Nephrol, 2002 Number of patients worldwide treated with chronic dialysis from 1990 to 2010 1990 2000 2010 426,000 1,490,000 2,500,000

4. Lysaght et al., J Am Soc Nephrol, 2002 1200 600 0 Medical costs for dialysis per decade in $ billions USD 1981-19901991-20002001-2010 800 1000 $ $ $ Predicted costs for chronic dialysis worldwide per decade from 1980 until 2010 400 200 $ $ $

5. Globally 1,800,000 patients with endstage renal failure 300,000,000 people with kidney malfunction (e.g. albuminuria), which gives them a markedly increased chance to develop heart failure and diabetes

6. World 1990 2020 10.6 m 20.2 m 4.1 m 5.6 m High inc. countries Mid/low inc. countries 6.5 m 14.5 m The Global Burden of Cardiovascular Disease Mortality (1990-2020) 4.1 5.7 1.4 0.6 1.3 0.6 3.6 1.6 3.9 2.0 0.8 2.0 1990 2020 * In million subjects 37% 144% 130% 119% 96% 139% 2.1 0.8 157%

7. World 2000 2030 154 m 370 m 55 m 84 m High inc. countriesMid/low inc. countries 99 m 286 m 16.7 33.8 32.9 18.2 52.4 30.7 28.3 9.1 80.9 22.8 42.3 18.6 0.91.6 2000 2030 * In million subjects 102% 81% 71% 211% 255% 127% 78% Increase of diabetes worldwide in the period 2000 to 2030 WHO, March 2003

8. Total Medicare Diabetes Heartfailure Dialysis/Tx CKD Numbers 5.8% 1.1% 20.7%25.1% 41.3%48.1% 19% 7.8% Kidney Failure, Heart Failure, and Diabetes; Number of patients and costs; USA 2002 Costs

9. Mild renal dysfunction is (Albuminuria and slight decrease in GFR) is highly prevalent StageDescription GFR (ml/min/1/73 m 2 ) Est. Prevalence USA Est. Prevalence NETHERLANDS 1 Albuminuria, normal or  GFR > 90 3.3%1.3% 2 Albuminuria, mild  GFR 60 - 89 3.0%3.8% 3 Moderate  GFR 30 - 594.3%5.3% 4 Severe  GFR 15 - 290.2%0.1% 5 Kidney Failure < 15 or RRT0.2%0.0% Total11.0%10.5% Coresh et al; Am J Kidney Dis 2004 De Zeeuw et al; Kidney Int; in press K/DOQI Clinical Practical Guidelines Am J Kidney Dis 2003

10. PREVEND; Albuminuria predicts moderate CKD (stage 3) (4 yr) >300 30 - 300 15 – 29 0 - 14 Stage 3 CKD (%) 70 60 50 40 30 20 10 0 Albuminuria (mg/day) 9 13 22 58 Verhave et al. Kidney Int 2004

11. PREVEND; Albuminuria predicts CV death in the general population (+3 yr) >300 30 - 300 15 – 29 0 - 14 CV death (% per 1000 pj) 35 30 25 20 15 10 5 0 Albuminuria (mg/day) 3.5 4.5 11.2 29.1 Hillege et al; Circulation 2002;106(14):1777-82

12. PREVEND; Albuminuria predicts new onset diabetes (4,2 yr) >300 30 - 300 15 – 29 0 - 14 New onset Diabetes (%) 14 12 10 8 6 4 2 0 Albuminuria (mg/day) Brantsma et al; Diabetes Care 2005 2.2 4.3 7.9 11.8

13. IRMA 2; Treatment associated with lowering of albuminuria reduces progression to diabetic nephropathy Parving H-H et al. N Engl J Med 2001;345:870–8. Follow-up (months) RiskReduction70% 0 0 3 3 6 6 12 18 22 24 0 0 5 5 10 15 20 Diabetic Nephropathy (%) Control + Conv tx AIIA (Irbesartan 150 mg) AIIA (Irbesartan 300 mg)

14. BENEDICT; Treatment associated with lowering of albuminuria reduces progression to microalbuminuria 0612182430364248 Months Placebo + Conv tx ACEi (trandolapril) 0 5 10 15 Transition to Microalbuminuria (%) Ruggenenti et al; N Engl J Med 2004 RiskReduction50%

15. Asselbergs et al; Circulation 2004 0 10203040 0.10 0.05 0 Placebo ACEi (fosinopril) CV mortality (%) Months PREVEND-IT; Treatment associated with lowering of albuminuria reduces CV mortality in the general populationRiskReduction44%

16. Meta-analysis; Treatment associated with albuminuria reduction reduces incidence of new onset diabetes Conventional BP lowering ACEi AII-A New onset Diabetes (% per 4.1 yr) 14 12 10 8 6 4 2 0 4.7 7.7 Lindholm LH; J Hypertens 2003 RiskReduction 39 %

17. PRIME; Early and Late intervention with AIIA are cost saving in type 2 diabetes Placebo + Conventional Tx Late AIIA (Irbesartan) Early AIIA (Irbesartan) Years since baseline age of 58 Cumulative costs per patient (€) 024681012141618202224 0 5,000 15,000 25,000 35,000 45,000 Palmer et al; Diabetes Care 2004

18. Conclusions  Early kidney failure is a common problem, affecting about 10% of the adult population  Early kidney failure is to detect with simple urine tests  Early kidney failure carries an increased risk for cardiovascular disease  Early kidney failure will ultimately result in need for dialysis and transplantation  When treatment (with generally available drugs) is started early, prevention of progressive renal and cardiac disease seems feasible  These approaches seem cost effective