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In the outcome trials that provided information on renal function in older hypertensive patients, diuretics and β-blockers were mostly used as first-line drugs. The long-term renal effects of calcium-channel blockers remain unclear.To compare the changes in renal function in 2258 treated and 2148 untreated patients with isolated systolic hypertension, of whom 455 had diabetes mellitus and 390 had proteinuria.We performed a post-hoc analysis of the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) Trial. Active treatment was initiated with nitrendipine (10–40 mg/day) with the possible addition of enalapril (5–20 mg/day), hydrochlorothiazide (12.5–25 mg/day), or both, titrated or combined to reduce the sitting systolic blood pressure by at least 20 mmHg, to less than 150 mmHg. The main outcome measures were serum creatinine concentration and creatinine clearance calculated by the formula of Cockroft and Gault.Serum creatinine concentration at the time when participants were randomly allocated to study groups was less than 176.8 μmol/l (2.0 mg/dl), averaging 88 μmol/l. At the time of the last serum creatinine measurement, the blood pressure difference (P< 0.001) between the two groups was 11.6/4.1 mmHg. In the intention-to-treat analysis (11 427 patient–years), serum creatinine and the calculated creatinine clearance were not influenced by active treatment. However, in the patients assigned randomly to receive active treatment, the incidence of mild renal dysfunction (serum creatinine at least 176.8 mmol/l) decreased by 64% (P= 0.04) and that of proteinuria by 33% (P= 0.03). Active treatment reduced the risk of proteinuria more in diabetic than in non-diabetic patients: by 71%, compared with 20% (P= 0 . 04). In non-proteinuric patients, active treatment did not influence serum creatinine, whereas in patients with proteinuria at entry to the study, serum creatinine decreased on active treatment (P< 0 . 001). Furthermore, in on-randomized treatment comparison stratified for risk at baseline, serum creatinine concentration did not change (P= 0.98) in patients continuing to receive monotherapy with nitrendipine, whereas it increased by 6.73 mmol/l (P< 0.001) in patients who received hydrochlorothiazide alone or in combination with other study medication (P< 0.001 for difference in trends).In older patients with isolated systolic hypertension, antihypertensive treatment starting with the dihydropyridine calcium-channel blocker, nitrendipine, did not decrease blood pressure at the expense of renal function and prevented the development of proteinuria, especially in diabetic patients.