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Nephrol Dial Transplant (2004) 19: 1803-1807
Nephrol Dial Transplant Vol. 19 No. 7 © ERA-EDTA 2004; all rights reserved

Original Article

Renal effects of N-acetylcysteine in patients at risk for contrast nephropathy: decrease in oxidant stress-mediated renal tubular injury

Luciano F. Drager1, Lúcia Andrade2, João Felipe Barros de Toledo1, Francisco R. M. Laurindo1, Luiz Antônio Machado César1 and Antonio Carlos Seguro2

1 Heart Institute (InCor) and 2 Department of Nephrology, Laboratory of Basic Research, School of Medicine, University of São Paulo, São Paulo, Brazil

Correspondence and offprint requests to: Antonio Carlos Seguro, MD, PhD, Faculdade de Medicina da USP, Av Doutor Arnaldo 455, sala 3310, 01246-903 São Paulo, Brazil. Email: trulu{at}usp.br

Background. N-Acetylcysteine has been shown to protect against contrast nephropathy, although the mechanisms underlying such an effect are unclear. Surprisingly, studies have shown that post-radiocontrast renal function actually improves in chronic renal failure patients receiving N-acetylcysteine. However, there have been no studies investigating the cause of this improvement.

Methods. In a double-blind, placebo-controlled study, 24 patients (aged 65±2 years) suffering from stable mild-to-moderate renal insufficiency and undergoing elective coronary angiography were randomized to receive either placebo or N-acetylcysteine. All received similar hydration. Renal function parameters were assessed 48 h before and 48 h after radiocontrast administration. Urinary 15-isoprostane F2t, a specific marker of oxidative stress, was measured immediately before and after the procedure. Expression of urinary {alpha}-glutathione S-transferase protein, a specific proximal tubular injury marker, was assessed after the procedure.

Results. Comparing creatinine clearance values before and after angiography, a significant increase was seen in N-acetylcysteine patients (44.7±4.2 vs 57.2±6.3 ml/min/1.73 m2; P = 0.02), whereas placebo patients presented no change (46.6±5.0 vs 46.9±4.3 ml/min/1.73 m2; P = 0.90). After radiocontrast, urinary 15-isoprostane F2t levels in placebo patients increased significantly over baseline values (2.9±0.7 vs 10.3±2.1 ng/mg creatinine; P = 0.007), whereas urinary 15-isoprostane F2t levels in N-acetylcysteine patients remained basically unchanged (3.5±0.5 vs 4.1±0.9 ng/mg creatinine; P = 0.63). Furthermore, N-acetylcysteine treatment led to lower levels of {alpha}-glutathione S-transferase than did placebo treatment (0.8±0.2 vs 2.4±0.7 µg/g; P = 0.046).

Conclusions. In chronic renal failure patients, the improvement in renal function induced by post-radiocontrast administration of N-acetylcysteine is strongly associated with suppression of oxidant stress-mediated proximal tubular injury.

Keywords: N-acetylcysteine; {alpha}-glutathione S-transferase; 15-isoprostane F2t; oxidative stress; radiocontrast; renal failure


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