ADDITIVE ANTIPROTEINURIC EFFECT OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITION AND NONSTEROIDAL ANTIINFLAMMATORY DRUG-THERAPY - A CLUE TO THE MECHANISM OF ACTION

1. Both the angiotensin-converting enzyme inhibitor, lisinopril, and the non-steroidal anti-inflammatory drug, indomethacin, lower urinary protein excretion in renal disease and improve the selectivity of the residual proteinuria. Despite the clearly different renal haemodynamic profiles of the two drugs, we hypothesize that the antiproteinuric effect has a final common pathway that is a reduction in glomerular filtration pressure.2. We studied the effects of lisinopril and indomethacin, separately and in combination, on urinary protein excretion, selectivity of proteinuria and renal haemodynamics in nine non-diabetic patients with overt proteinuria.3. Urinary protein excretion was 5.4 +/- 2.5 g/24 h in the control period. Lisinopril monotherapy lowered urinary protein excretion by 53 +/- 26%. During indomethacin treatment urinary protein excretion was reduced by 63 +/- 24%. After adding indomethacin to lisinopril, urinary protein excretion fell by a further 58 +/- 23%, resulting in a 79 +/- 17% decrease during combined therapy.4. Although both lisinopril and indomethacin monotherapy appeared to result in an improvement in glomerular protein permselectivity, no further improvement was seen during the combination therapy.5. The changes in proteinuria were associated with changes in glomerular filtration rate, which showed a pronounced fall with combination therapy. The renal haemodynamic profiles during the different therapies suggest a post-glomerular vasodilatation by lisinopril and a pre-glomerular vasoconstriction by indomethacin, and the combination of both during the combined treatment.6. These data suggest a synchronous afterload and preload reduction of glomerular filtration pressure as the cause of the additive effect of the combination of angiotensin-converting enzyme inhibition and non-steroidal anti-inflammatory drug therapy in lowering glomerular filtration rate and proteinuria.