Efonidipine, a dihydropirydine calcium channel blocker, has been shown to dilate the efferent glomerular arterioles as effectively as the afferent arterioles. The present study compared the chronic effects of efonidipine and amlodipine on proteinuria in patients with chronic glomerulonephritis. The study subjects were 21 chronic glomerulonephritis patients presenting with spot proteinuria greater than 30 mg/dL and serum creatinine concentrations of <or=1.3 mg/dL in men or <or=1.1 mg/dL in women. All patients were receiving antihypertensive medication or had a blood pressure >or=130/85 mmHg. Efonidipine 20-60 mg twice daily and amlodipine 2.5-7.5 mg once daily were given for 4 months each in a random crossover manner. In both periods, calcium channel blockers were titrated when the BP exceeded 130/85 mmHg. Blood sampling and urinalysis were performed at the end of each treatment period. The average blood pressure was comparable between the efonidipine and the amlodipine periods (133+/-10/86+/-5 vs. 132+/-8/86+/-5 mmHg). Urinary protein excretion was significantly less in the efonidipine period than in the amlodipine period (1.7+/-1.5 vs. 2.0+/-1.6 g/g creatinine, p=0.04). Serum albumin was significantly higher in the efonidipine period than the amlodipine period (4.0+/-0.5 vs. 3.8+/-0.5 mEq/L, p=0.03). Glomerular filtration rate was not significantly different between the two periods. Plasma aldosterone was lower in the efonidipine period than in the amlodipine period (52+/-46 vs. 72+/-48 pg/mL, p=0.009). It may be concluded that efonidipine results in a greater reduction of plasma aldosterone and proteinuria than amlodipine, and that these effects occur by a mechanism independent of blood pressure reduction. A further large-scale clinical trial will be needed in order to apply the findings of this study to the treatment of patients with renal disease.