Effects of benidipine on glomerular hemodynamics and proteinuria in patients with nondiabetic nephropathy

Experimental studies suggest that some long-acting calcium antagonists decrease glomerular hypertension and suppress the progression of nephropathy, but clinical evidence is lacking. To investigate clinically whether a long-acting calcium antagonist, benidipine, lowers glomerular capillary hydraulic pressure via a decrease in efferent arteriolar resistance and decreases proteinuria, we examined hypertensive patients with nondiabetic nephropathy. The subjects were 7 patients with chronic glomerulonephritis or glomerulosclerosis. Before and during the administration of benidipine (4 mg/day), systemic pressure, glomerular hemodynamics, the sodium sensitivity index (reciprocal of the pressure-natriuresis curve), and urinary excretion of proteins (total protein, albumin, and immunoglobulin G) were investigated. The glomerular hemodynamics in terms of glomerular capillary hydraulic pressure and resistance of afferent and efferent arterioles were calculated from the renal clearance, plasma total protein concentration, and pressure-natriuresis relationship. Benidipine lowered the mean arterial pressure from 105 +/-5 to 99 +/- 4 mm Hg (p = 0.002; mean +/- SD) and glomerular pressure from 48 +/- 8 to 39 +/- 5 mmHg (p = 0.006) by decreasing the resistance of efferent arterioles. Benidipine made the pressure-natriuresis curve steeper and decreased the median sodium sensitivity index from 0.099 (0.084 and 0.117; 25th and 75th percentiles) to 0.048 (0.017 and 0.058; p = 0.018). Urinary excretion of proteins did not change. Our clinical study showed that benidipine lowered the glomerular pressure by decreasing the resistance of efferent arterioles and decreased the sodium sensitivity of blood pressure, but did not affect proteinuria in patients with nondiabetic nephropathy.