dihydropyridines and Glomerulonephritis--Membranoproliferative

Topics: Adult; Antihypertensive Agents; Ascitic Fluid; Calcium Channel Blockers; Cardiovascular Agents; Chylous Ascites; Diagnosis, Differential; Dihydropyridines; Drug Therapy, Combination; Female; Glomerulonephritis, Membranoproliferative; Humans; Kidney Failure, Chronic; Nifedipine; Nitrobenzenes; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Piperazines; Retrospective Studies; Triglycerides

Although the renoprotective effect of calcium-channel blockers (CCBs) has been examined in several models of hypertensive nephropathy, it remains unclear. It also remains to be clarified whether CCBs prevent the progression to end-stage renal failure in chronic progressive glomerulonephritis (GN). A new rat model of progressive mesangioproliferative GN was used to study the effect of benidipine hydrochloride, a long-acting dihydropyridine CCB, on the clinical features and morphological lesions.. This animal model of progressive GN was induced by a single intravenous injection of anti-Thy-1 monoclonal antibody (MoAb 1-22-3) two weeks after unilateral nephrectomy. After 10 weeks of treatment with benidipine (1, 3, and 5 mg/kg body weight, p.o.) or hydralazine (5 mg/kg body weight, p.o.), systolic blood pressure (SBP), urinary protein excretion, creatinine clearance, glomerulosclerosis index, tubulointerstitial lesion index, glomerular cross-sectional area, and glomerular expression of transforming growth factor-beta (TGF-beta) and alpha-smooth muscle actin (alpha-SMA) were measured.. Untreated rats developed hypertension, massive proteinuria, renal dysfunction, severe glomerular and tubulointerstitial injury, higher glomerular size, and marked glomerular staining for TGF-beta and alpha-SMA, while uninephrectomized control rats did not. Each dose of benidipine and hydralazine equally reduced SBP to uninephrectomized control levels. Three and five mg/kg/day of benidipine increased creatinine clearance, ameliorated glomerular and tubulointerstitial injury, and reduced glomerular staining for TGF-beta and alpha-SMA, but 1 mg/kg/day of benidipine and hydralazine failed. Only a dose of 5 mg/kg/day of benidipine reduced glomerular size, although it did not reduce the size to control levels.. These results indicate that in a rat model of progressive mesangioproliferative GN, benidipine prevents the progression to end-stage renal failure in a dose-dependent manner. This renoprotective action is associated with the suppression of glomerular expression of TGF-beta and alpha-SMA.

Topics: Actins; Animals; Blood Pressure; Body Weight; Calcium Channel Blockers; Creatinine; Dihydropyridines; Disease Models, Animal; Disease Progression; Fluorescent Antibody Technique; Glomerulonephritis, Membranoproliferative; Hydralazine; Kidney Failure, Chronic; Kidney Glomerulus; Male; Nephrectomy; Proteinuria; Rats; Rats, Wistar; Transforming Growth Factor beta; Vasodilator Agents