OBJECTIVE This study aimed to investigate the renoprotective effect on diabetic nephropathy of a novel class of Ca(2+) channel blocker, cilnidipine, that inhibits both L-type and N-type Ca(2+) channels; a conventional L-type Ca(2+) channel blocker was substituted with cilnidipine in type 2 diabetic patients with albuminuria. METHODS Urinary albumin index (UAI), serum creatinine, and blood pressure were measured in 38 outpatients with type 2 diabetes receiving amlodipine, an L-type Ca(2+) channel blocker, in addition to an angiotensin I converting enzyme inhibitor and/or an angiotensin type 1 receptor blocker. Amlodipine was then substituted with cilnidipine, and the same parameters were measured after 3 months. RESULTS Although blood pressure was not significantly changed after substitution with cilnidipine, log-transformed UAI was significantly decreased (P=.004) with a mean reduction of 28% [95% confidence interval (CI)=11-42]. Serum creatinine was significantly (P=.04) increased (from 0.82+/-0.22 to 0.86+/-0.23 mg/dl). When the subjects were divided into two groups according to the change in serum creatinine, UAI change was significant only in those with an increase in serum creatinine, who exhibited a mean reduction of UAI of 39% (95% CI=16-56, P=.005), but not in those without an increase in serum creatinine, whose mean reduction of UAI was 18% (95% CI=-12 to 40, P=.2). CONCLUSIONS In patients with diabetic nephropathy, blocking N-type Ca(2+) channels with a new class of Ca(2+) channel blocker resulted in a significant reduction in albuminuria, suggesting a renoprotective effect of N-type Ca(2+) channel blockade, even when combined with renin-angiotensin inhibition.