The antiproteinuric effect of angiotensin antagonism in human IgA nephropathy is potentiated by indomethacin.
Evidence is available from animal and human studies that protein traffic through the glomerular capillary has a pathogenetic role in subsequent renal damage and that angiotensin-converting enzyme (ACE) inhibitors appear superior to other drugs in lowering proteinuria and the rate of renal function decline. This study compares the effect of ACE inhibition or angiotensin II (AngII) receptor blockade on urinary protein excretion and renal hemodynamics in 20 patients with IgA glomerulonephritis randomized to receive enalapril (20 mg/d) or irbesartan (100 mg/d) for 28 d in a double-blind study with two parallel groups. This study also evaluated whether addition of indomethacin (75 mg twice a day) to each of the two treatments resulted in a more potent antiproteinuric effect. Enalapril alone reduced total protein excretion (61% change from baseline) and fractional clearance of albumin without changes in GFR and minor elevation in renal plasma flow. Also, patients randomized to receive the AngII receptor antagonist irbesartan for 28 d had lower proteinuria (55% change from baseline) and fractional clearance of albumin at the end of the treatment period with similar renal hemodynamic changes. When indomethacin was added to enalapril treatment, a further significant reduction in urinary proteins and fractional albumin clearance was observed. In patients given irbesartan, the addition of indomethacin further reduced proteinuria and fractional clearance of albumin. The combined therapy with enalapril or irbesartan and indomethacin did not significantly affect GFR and renal plasma flow compared with baseline. These findings indicate that in patients with IgA glomerulonephritis the antiproteinuric effect of blocking AngII activity by either ACE inhibitors or AngII receptor antagonists is potentiated by indomethacin, an effect that occurred without impairment of renal function.
Perico
N
N
Department of Kidney Research, Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Remuzzi
A
A
Sangalli
F
F
Azzollini
N
N
Mister
M
M
Ruggenenti
P
P
Remuzzi
G
G
D000328:Adult; D000368:Aged; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure; D004311:Double-Blind Method; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005922:Glomerulonephritis, IGA / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D006977:Hypertension, Renal / Q000209:etiology; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000077405:Irbesartan; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000209:etiology / Q000517:prevention & control*; D012079:Renal Circulation / Q000187:drug effects; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D013777:Tetrazoles; D004656:Enalapril; D000077405:Irbesartan; D007213:Indomethacin