A randomized and double-blind comparison of isradipine and spirapril as monotherapy and in combination on the decline in renal function in patients with chronic renal failure and hypertension

Aims: Treatment of hypertension in patients with chronic renal failure has been shown to postpone the decline in renal function. Treatment with an ACE inhibitor has been shown to be superior to conventional antihypertensive t reatment, but it is not known how an ACE inhibitor compares to treatment wi th a calcium channel blocker or to treatment with a combination of these dr ugs. The aim of the study was to evaluate the rate of decline in GFR in pat ients with chronic renal failure and hypertension treated with isradipine a nd spirapril as monotherapy and in combination. Methods: Sixty patients wit h chronic renal failure and hypertension were enrolled in the study. After enrollment, patients were followed prospectively for 6 months in the outpat ient clinic on their usual antihypertensive medication, and then randomized to a double-blinded comparison of either spirapril 6 mg daily, isradipine 5 mg daily or spirapril 3 mg and isradipine 2.5 mg daily. After randomizati on, patients were followed for 21 months or until the need for dialysis. Ev ery 3 months before and 3.5 months after randomization the glomerular filtr ation rate was measured by Cr-51-EDTA clearance and the effective renal pla sma flow evaluated using the renal clearance of paraaminohippuric acid. Res ults: Blood pressure and the decline in glomerular filtration rate did not differ between the groups before randomization. After randomization, the me an decline in the glomerular filtration rate was -0.32 ml/(min x month x 1. 73 m(2)) in the spirapril group, -0.58 ml/(min x month x 1.73 m(2)) in the isradipine group and -0.14 ml/(min x month x 1.73 m(2)) in the combination group (p = 0.38). Twelve patients, 4 in each group, reached end-stage renal failure. No significant difference was found with respect to diastolic (p = 0.10) or systolic blood pressure (p = 0.08) during, the treatment period, but a trend towards a better blood pressure control in the combination gro up was present. During treatment, the rate of decline in renal plasma flow did not differ significantly between the groups (p = 0.09), neither did the changes in filtration fi-action (FF) (p = 0.58) nor the mean FF (p = 0.22) during the treatment. Conclusions: Our study indicated differences between the 3 treatment modalities in favor of combined therapy with respect to bo th the rate of decline in GFR and blood pressure control, but the differenc es where insignificant. Thus, the treatments might differ, but we were unab le to confirm this because of large variation in GFR and small sample size.