lacidipine and Proteinuria

A total of 30 patients with diabetic nephropathy were examined together with 30 patients presenting with chronic glomerulonephritis at different stages of the condition. An unquestionable positive effect has been demonstrated of lacidipine on the arterial pressure, glomerular filtration rate, proteinuria, diuresis, excretion of nitrogenous metabolities in patients with the above pathology presenting with the normal or impaired renal function. A prognostic criterion has been developed for efficiency of treatment with lacidipine making use of the corinfar test.

Topics: Adolescent; Adult; Blood Pressure; Calcium Channel Blockers; Chronic Disease; Diabetic Nephropathies; Dihydropyridines; Female; Glomerular Filtration Rate; Glomerulonephritis; Humans; Kidney Glomerulus; Male; Middle Aged; Proteinuria; Treatment Outcome

In proteinuric nephropathies tubular atrophy leads to glomerular-tubule disconnection through an unknown mechanism. Here we studied whether proteinuria promoted glomerular-tubule disconnection in individual nephrons and whether this phenomenon was prevented by an angiotensin-converting enzyme (ACE) inhibitor. Passive Heymann nephritis (PHN) and control rats were studied at 4 and 8 months. Two additional groups of PHN rats received lisinopril (40 mg/L) or a calcium channel blocker (lacidipine, 3 mg/kg) from day 7 after surgery to 8 months. At sacrifice, kidneys were serially sectioned to identify glomerular- tubule abnormalities in individual nephrons and changes in interstitial volume. In PHN rats, the time-dependent increase in proteinuria was paralleled by tubular atrophy leading to glomerular-tubule disconnection and interstitial volume enlargement. Marked apoptosis was invariably found in atrophic tubules in contrast to the absent or very mild terminal dUTP nick-end labeling staining in tubules normally connected to glomeruli in PHN animals. Treatment with an ACE inhibitor prevented hypertension, proteinuria, the formation of atrophic tubuli, glomerular-tubule disconnection and limited the fractional interstitial volume expansion. Although lacidipine limited hypertension, it did not reduce proteinuria or prevent tubular atrophy and disconnection. Multivariate analysis showed that the appearance of atubular glomeruli and the increase in interstitial volume were better predicted by proteinuria than blood pressure. This study suggests that ACE inhibitors effectively prevent glomerular-tubule disconnection possibly by their ability of reducing proteinuria, which in turn favors proximal tubular cell apoptosis. Agents that only reduced hypertension but not proteinuria do not affect tubular behavior.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Apoptosis; Atrophy; Calcium Channel Blockers; Dihydropyridines; Glomerulonephritis; Kidney; Kidney Glomerulus; Kidney Tubules; Lisinopril; Male; Proteinuria; Rats; Rats, Sprague-Dawley; Reference Values

Lacidipine is a second-generation 1,4-dihydropyridine calcium antagonist, whose potent and long-lasting antihypertensive properties prompted us to investigate whether its chronic administration to Dahl-S rats prevented salt-induced hypertension, vasculopathy, and accelerated mortality. These studies revealed that lacidipine proved vasoprotective when administered both prophylactically and therapeutically at doses of 0.1 and 0.3 mg/kg p.o. once a day, largely equivalent to the therapeutic doses. A generalized dose-related protection against necrotizing vasculopathy and brain damage was detected, although only the highest dose used (10 mg/kg) controlled the development of hypertension. These protective properties were further confirmed in stroke-prone spontaneously hypertensive rats, which develop accelerated mortality as a result of salt-induced cerebral apoplexy and renal lesions. All untreated controls died within 12 weeks of salt-rich diet, whereas all animals survived during the same period when treated prophylactically with lacidipine at 0.3 and 1 mg/kg p.o. once a day, although a slight reduction in systolic blood pressure was measured only with the highest dose. No cerebral lesions and a clear protection against renal damage were detected in lacidipine-treated animals. In conclusion, these findings reinforce the concept that the beneficial effects of calcium antagonists are not simply restricted to a reduction in blood pressure.

Topics: Animals; Calcium Channel Blockers; Desoxycorticosterone; Dihydropyridines; Hypertension; Kidney; Proteinuria; Rats; Rats, Inbred Strains