Comparison between cilnidipine and amlodipine besilate with respect to proteinuria in hypertensive patients with renal diseases

Abstract

Unlike other dihydropyridine calcium channel blockers (CCBs), cilnidipine has been reported to exert an N-type calcium-channel-blocking activity and to reduce sympathetic hyperactivity. This study compared cilnidipine and amlodipine with respect to their effects on renal function and proteinuria. Twenty-eight proteinuric hypertensive outpatients (13 men and 15 women, aged 62+/-2 years) who had been maintained on CCBs for more than 3 months were randomly assigned to a group receiving amlodipine besilate (14 patients) or a group receiving cilnidipine (14 patients). CCBs were increased in dosage or other drugs were added until blood pressure decreased below 140/90 mmHg, but no inhibitors of the renin-angiotensin (RA) system were added or changed in dosage. Before and at 6 and 12 months after randomization, the concentrations of urine protein, urine albumin, serum and urine creatinine (Cr), and serum beta2-microglobulin were determined. The amlodipine group showed a significant increase in proteinuria, while the increase was suppressed in the cilnidipine group. The rate of increase in proteinuria at 12 months was 87% (95% confidence interval (CI) -10 to 184) of the baseline value with amlodipine and 4% (95% CI -69 to 77) of baseline with cilnidipine, a significant intergroup difference (p<0.05). The mean blood pressure remained in the 96-99 mmHg range until 12 months after randomization, showing no significant difference between the two groups. The cilnidipine group showed an increase in serum Cr levels (baseline vs. 12 months, 1.36+/-0.20 vs. 1.50+/-0.23 mg/dl, p<0.01). Overall, an inverse correlation existed between the changes in Cr and proteinuria (r= -0.477, p<0.01). These results suggest that cilnidipine results in a greater suppression of the increase in proteinuria and greater reduction in glomerular filtration rate than amlodipine, and that these effects are similar between cilnidipine and RA inhibitors. However, additional large-cohort and longer-term studies will be needed to clarify whether cilnidipine is superior to other CCBs in maintaining renal function.