Renal effects of N-acetylcysteine in patients at risk for contrast nephropathy: decrease in oxidant stress-mediated renal tubular injury.
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 F2(t), 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 m(2); P = 0.02), whereas placebo patients presented no change (46.6+/-5.0 vs 46.9+/-4.3 ml/min/1.73 m(2); P = 0.90). After radiocontrast, urinary 15-isoprostane F2(t) 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 F2(t) 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 micro g/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.
Drager
Luciano F
LF
Heart Institute (InCor),School of Medicine, University of São Paulo, São Paulo, Brazil.
Andrade
Lúcia
L
Barros de Toledo
João Felipe
JF
Laurindo
Francisco R M
FR
Machado César
Luiz Antônio
LA
Seguro
Antonio Carlos
AC
D000111:Acetylcysteine / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003287:Contrast Media / Q000009:adverse effects*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000378:metabolism; D007684:Kidney Tubules / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D012307:Risk Factors
D003287:Contrast Media; D000111:Acetylcysteine