EFFECT OF INCREASING DOSES OF LISINOPRIL ON PROTEINURIA OF NORMOTENSIVE PATIENTS WITH IGA NEPHROPATHY AND NORMAL RENAL-FUNCTION

The antiproteinuric effect of angiotensin converting enzyme (ACE) inhi bition in patients with renal disease is well known, but the results o f clinical studies appear to vary considerably from a partial decrease to a fall of 100% in urinary protein excretion. This may have been du e to the use of different doses of ACE inhibitor, different renal path ology and non-standardized sodium intake. In 16 proteinuric patients w ith biopsy-proven IgA nephropathy, with normal renal function and bloo d pressure, maintained at controlled sodium intake less than or equal to 80 mEq/l, the efficacy of increasing doses of the ACE inhibitor lis inopril was studied. The lisinopril doses were 5, 10, 15 and 20 mg, ad ministered for 4 weeks. Between each dose increment a placebo period o f 3 weeks was interposed. Proteinuria stepwise decreased from the cont rol period by 39%, 44%, 61% and 67% with lisinopril at 5, 10, 15 an 20 mg, respectively. The blood pressure decreased by 22% with lisinopril 5 mg; a similar fall was observed with the dose increment. Although t he glomerular filtration rate remained unchanged, the renal plasma flo w increased by 21%, 26%, 24% and 28% and the filtration fraction incre ased by 28% mean. The ACE plasma levels decreased by 33%, 64%, 76% and 83%. A close correlation was found between an increase in lisinopril dosage and the fall in urinary protein excretion (r = 0.88, p < 0.001) . The antiproteinuric effect of lisinopril is dose-related and may be attributable to some extent to the fall in systemic (and intraglomerul ar) blood pressure, but it is best attributed to the modification of g lomerular sieving function. The dose of ACE inhibitors for the treatme nt of renal proteinuric patients must progressively increase to elicit the maxim effect.