Antiproteinuric effect of an L/N-type calcium channel blocker, cilnidipine, with special reference to the combination therapy with ACE inhibitors or ARBs

We investigated the long-term antiproteinuric effect of an L/N-type calcium channel (Ca) blocker, cilnidipine in the patients with essential hypertension (EHT). Subjects are 37 EHT patients (61±2 (SE) years, 22 females and 15 males). All patients underwent 24-h home urine collection and proved to have proteinuria greater than 0.1 g/day. Cilnidipine at a mean dose of 8 mg was administered to the patients. In 30 patients, cilnidipine was switched from other Ca antagonists including manidipine and amlodipine, while cilnidipine was newly added in the other 7 patients. Seventeen patients have been received either ACE inhibitors (ACEI) or ARBs at least 6 months before the administration of cilnidipine. Blood pressure (BP), blood chemistry and 24-h home urine collection were determined at 6, 12 and 24 months after the administration of cilnidipine. Baseline BP was 142±2/85±1 mmHg. Systolic BP did not change significantly throughout the study, while diastolic BP was significantly lower at 6 months (82±1 mmHg, p < 0.01), 12 months (84±1 mmHg, p < 0.05) and 24 months (82±2 mmHg, p < 0.05). Urinary protein excretion decreased significantly from 0.36±0.04 g/day to 0.16±0.02 g/day(-45.7±6.7%, p < 0.01) at 6 months and to 0.14±0.04 g/day (-57.8±12.0%, p < 0.01) at 12 months. The reduction of proteinuria occurred independently of the changes in BP. Urinary salt excretion, estimated protein intake, and serum creatinine concentration did not change significantly during the observation period. The reduction of proteinuria at 6 months after cilnidipine was similar between the patients with the baseline administration of ACEI/ARB (-47.6±11.2%, p < 0.01) and those without ACEI/ARB (-44.4±8.7%, p < 0.01). On the other hand, the reduction of proteinuria continued until 24 months in the patients with ACEI/ARB (-41.1±16.3%, p < 0.05) but not in those without ACEI/ARB (-9.3 ±49.1%, ns). Results suggest that cilnidipine exerts antiproteinuric effect irrespectively of the co-administration of ACEI/ARB. However, the effect of cilnidipine may last longer in the presence of ACEI/ARB.