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

Lysaght et al., J Am Soc Nephrol, Medical costs for dialysis per decade in $ billions USD $ $ $ Predicted costs for chronic dialysis worldwide per decade from 1980 until $ $ $

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

World 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 ( ) * In million subjects 37% 144% 130% 119% 96% 139% %

World m 370 m 55 m 84 m High inc. countriesMid/low inc. countries 99 m 286 m * In million subjects 102% 81% 71% 211% 255% 127% 78% Increase of diabetes worldwide in the period 2000 to 2030 WHO, March 2003

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

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 > %1.3% 2 Albuminuria, mild  GFR %3.8% 3 Moderate  GFR %5.3% 4 Severe  GFR %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

PREVEND; Albuminuria predicts moderate CKD (stage 3) (4 yr) > – Stage 3 CKD (%) Albuminuria (mg/day) Verhave et al. Kidney Int 2004

PREVEND; Albuminuria predicts CV death in the general population (+3 yr) > – CV death (% per 1000 pj) Albuminuria (mg/day) Hillege et al; Circulation 2002;106(14):

PREVEND; Albuminuria predicts new onset diabetes (4,2 yr) > – New onset Diabetes (%) Albuminuria (mg/day) Brantsma et al; Diabetes Care

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% Diabetic Nephropathy (%) Control + Conv tx AIIA (Irbesartan 150 mg) AIIA (Irbesartan 300 mg)

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

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

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) Lindholm LH; J Hypertens 2003 RiskReduction 39 %

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 (€) ,000 15,000 25,000 35,000 45,000 Palmer et al; Diabetes Care 2004

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