NITROFLURBIPROFEN, A NEW NONSTEROIDAL ANTIINFLAMMATORY, AMELIORATES STRUCTURAL INJURY IN THE REMNANT KIDNEY

Cyclooxygenase derivatives and nitric oxide (NO) may influence the pat hogenesis of progressive nephropathies. We investigated the effect of nitroflurbiprofen (NOF), a NO-releasing nonsteroidal anti-inflammatory drug (NSAID) without gastrointestinal toxicity, in rats with 5/6 abla tion (NX). The following four groups were studied: Sham, sham-operated rats; Sham + NOF, Sham receiving oral NOF two times daily; NX, rats s ubjected to NX; and NX + NOF, NX receiving NOF. NOF was barely detecte d in plasma but released the parent compound flurbiprofen. At 30 days, glomerular hydraulic pressure (P-GC) was 76 +/- 3 mmHg in NX (52 +/- 1 in Sham, P < 0.05). NOF slightly reduced P-GC to 69 +/- 2 mmHg in NX + NOF (P > 0.05 vs. NX). Glomerular volumes behaved similarly. At 60 days, tail cuff pressure was 152 +/- 6 mmHg, glomerulosclerosis index was 22.1 +/- 9.5, and interstitial fractional area was 9.9 +/- 1.2% in NX. NOF reduced these parameters to 137 +/- 4 mmHg, 3.5 +/- 0.7, and 6.4 +/- 0.8%, respectively (P < 0.05), without causing growth stunting or anemia. These beneficial effects could not be ascribed to NO donat ion and may reflect cyclooxygenase inhibition. This is the first evide nce that chronic NSAID treatment may ameliorate progressive nephropath ies.