ISRADIPINE IN CHRONIC-RENAL-FAILURE - ANTIHYPERTENSIVE EFFECT AND RENAL PROTECTION

Arterial hypertension is regarded as a major factor in the progression of chronic renal failure. Hyperfiltration in the surviving nephrons and increased protein leakage across the glomerular capillaries are thought to play a pathogenetic role, The effects of long-term treatment with the sustained-release formulation (SRO) of isradipine on blood pressure, renal function, and protein excretion were evaluated in patients with mild-to-moderate arterial hypertension and chronic renal failure (creatinine clearance 30 to 60 mL/min/1.73 m(2)). Sixty-two patients (mean +/- SD age, 56 +/- 11 years) were included in the study. After a 14-day placebo period, a single 2.5-mg dose of isradipine SRO was administered each morning for 2 weeks. The dose was then increased to 5 mg/d if supine diastolic blood pressure (DBP) was greater than or equal to 95 mm Hg; if adequate blood pressure control was not achieved, atenolol 25 to 100 mg or captopril 25 to 50 mg was added beginning at week 9. Thirtysix patients continued monotherapy throughout the study. After 8 weeks, mean casual blood pressure reduction was 10/7 mm Hg (P < 0.001). In all patients, systolic blood pressure (SEP) decreased from 166 +/- 17 mm Hg to 146 +/- 12 mm Hg (P < 0.001) and DBP from 101 +/- 7 mm Hg to 89 +/- 6 mm Hg (P < 0.001) at week 24 compared with baseline values. Mean 24-hour automatic ambulatory blood pressure decrease was 7/3 mm Hg at week 8 and 15/7 mm Hg at week 24 compared with baseline values (P < 0.001). The glomerular filtration rate remained unchanged during the study; the mean serum creatinine concentration was 1.94 mg/dL (171 mu mol/L) at week 24 versus 1.87 mg/dL (154 mu mol/L) at baseline (P = NS). Proteinuria decreased, although statistical significance was not achieved; median value for protein excretion in the urine collected during the night at week 24 was 361 mg compared with 755 mg at baseline (P = 0.07). A similar decrease was apparent for protein fractions with different molecular weights (albumin, alpha(1)-microglobulin, retinol-binding protein, and beta(2)-microglobulin). Six patients (10%) reported minor side effects (flushing, ankle edema), none of which caused discontinuation of therapy. Long-term therapy with isradipine SRO is effective and well tolerated in patients with chronic renal failure; in addition, renal function appears to be preserved. Blood pressure reduction appears to favorably affect proteinuria and albuminuria; decreases in both are also desirable in antihypertensive therapy.