Background: The severity of proteinuria is the main predictive factor in the progression of renal failure in chronic nephropathies. Therefore, action aimed at reducing proteinuria should be a priority in the treatment of these patients. Various antihypertensive drugs, in particular the angiotensin-converting enzyme inhibitors (ACEIs), have a greater antiproteinuric effect, although it is difficult to establish whether this is due only to their effect on arterial blood pressure (BP) or to other mechanisms associated with blockade of the renin-angiotensin system (RAS).
Methods: The evolution of proteinuria after two successive treatment periods was studied prospectively for 2 years in 22 patients with chronic glomerulonephritis. In period I, which lasted for 12 months, BP was strictly controlled (<125/75 mmHg) and the patients received random and double-blind treatment with a beta-blocker (betaB), atenolol; a non-dihydropyridine calcium channel blocker (CCB), verapamil; an ACEI, trandolapril; or a fixed combination of the latter two. In period II, all of the patients received treatment openly for an additional 12 months with a fixed combination of verapamil+trandolapril at half the dose of the preceding period, to obtain conventional control of BP at <140/90 mmHG:
Results: The mean level for basal SBP/DBP was 136+/-14/86+/-7 mmHg, which decreased in period I to 121+/-15/76+/-8 mmHg (P=0.01) and to 124+/-5/78 +/-8 mmHg (P<0.05) at 6 and 12 months of treatment, respectively. There were no differences in the BP reached in the four therapy groups; however, proteinuria only decreased in the patients treated with trandolapril alone or in combination with verapamil. In period II, BP levels rose to 134+/-10/84+/-8 mmHg (P<0.05); this increase in BP was accompanied by an increase in proteinuria in those patients who had received the ACEI alone or in combination in the previous period, while in patients previously treated with a betaB or a CCB, proteinuria decreased, in spite of the increase in BP.
Conclusions: With equal BP control, treatment with the ACEI trandolapril alone, or in combination with a CCB, has a greater antiproteinuric effect than that obtained with other antihypertensive drugs, but this effect is attenuated if BP is not strictly controlled.