Adverse effect of indomethacin in experimental chronic nephrosis.

The effects of long-term indomethacin therapy were studied in rats with chronic nephrosis induced by puromycin of aminonucleoside (PAN). Fifteen PAN rats received indomethacin (2 mg/kg/d) administered by daily gavages, and fifteen received glucose. A control group received indomethacin but no PAN. Three to five animals per group were sacrificed monthly. Proteinuria was similar in both PAN rat groups. Renal function and histology were normal in the control rats. In the PAN animals, renal failure developed earlier in the treated rats than in the others. Histological examination revealed in all PAN rats early tubulo-interstitial lesions and progressive glomerular damage. The pattern of the lesions was identical in both PAN rats, but the glomerular changes developed earlier, were more diffuse and more severe in the indomethacin treated rats. Thus, indomethacin resulted in an accelerated destruction of the glomeruli in experimental nephrosis. Such a deleterious effect remains unexplained, and its relevance to human disease is not demonstrated.