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 a nd increased protein leakage across the glomerular capillaries are tho ught to play a pathogenetic role, The effects of long-term treatment w ith the sustained-release formulation (SRO) of isradipine on blood pre ssure, renal function, and protein excretion were evaluated in patient s with mild-to-moderate arterial hypertension and chronic renal failur e (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 ad ministered each morning for 2 weeks. The dose was then increased to 5 mg/d if supine diastolic blood pressure (DBP) was greater than or equa l to 95 mm Hg; if adequate blood pressure control was not achieved, at enolol 25 to 100 mg or captopril 25 to 50 mg was added beginning at we ek 9. Thirtysix patients continued monotherapy throughout the study. A fter 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 baseli ne values. Mean 24-hour automatic ambulatory blood pressure decrease w as 7/3 mm Hg at week 8 and 15/7 mm Hg at week 24 compared with baselin e values (P < 0.001). The glomerular filtration rate remained unchange d during the study; the mean serum creatinine concentration was 1.94 m g/dL (171 mu mol/L) at week 24 versus 1.87 mg/dL (154 mu mol/L) at bas eline (P = NS). Proteinuria decreased, although statistical significan ce was not achieved; median value for protein excretion in the urine c ollected during the night at week 24 was 361 mg compared with 755 mg a t baseline (P = 0.07). A similar decrease was apparent for protein fra ctions with different molecular weights (albumin, alpha(1)-microglobul in, retinol-binding protein, and beta(2)-microglobulin). Six patients (10%) reported minor side effects (flushing, ankle edema), none of whi ch caused discontinuation of therapy. Long-term therapy with isradipin e SRO is effective and well tolerated in patients with chronic renal f ailure; in addition, renal function appears to be preserved. Blood pre ssure reduction appears to favorably affect proteinuria and albuminuri a; decreases in both are also desirable in antihypertensive therapy.