Acetylcysteine and Renal Function Following Coronary Angiographic Procedures

The University of Calgary, Calgary, Alberta, Canada
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 07/2003; 289(21):2795; author reply 2796. DOI: 10.1001/jama.289.21.2795-a
Source: PubMed
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    ABSTRACT: 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. 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. 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). 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.
    Full-text · Article · Aug 2004 · Nephrology Dialysis Transplantation
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    ABSTRACT: Contrast-induced nephropathy is an important cause of acute renal failure. We assess the efficacy of acetylcysteine for prevention of contrast-induced nephropathy among patients undergoing intravascular angiography. We conducted a systematic review and meta-analysis of randomized controlled trials comparing prophylactic acetylcysteine plus hydration versus hydration alone in patients undergoing intravascular angiography. Studies were identified by searching MEDLINE, EMBASE, and CENTRAL databases. Our main outcome measures were the risk of contrast-induced nephropathy and the difference in serum creatinine between acetylcysteine and control groups at 48 h. Fourteen studies involving 1261 patients were identified and included for analysis, and findings were heterogeneous across studies. Acetylcysteine was associated with a significantly reduced incidence of contrast-induced nephropathy in five studies, and no difference in the other nine (with a trend toward a higher incidence in six of the latter studies). The pooled odds ratio for contrast-induced nephropathy with acetylcysteine relative to control was 0.54 (95% CI, 0.32-0.91, p = 0.02) and the pooled estimate of difference in 48-h serum creatinine for acetylcysteine relative to control was -7.2 mumol/L (95% CI -19.7 to 5.3, p = 0.26). These pooled values need to be interpreted cautiously because of the heterogeneity across studies, and due to evidence of publication bias. Meta-regression suggested that the heterogeneity might be partially explained by whether the angiography was performed electively or as emergency. These findings indicate that published studies of acetylcysteine for prevention of contrast-induced nephropathy yield inconsistent results. The efficacy of acetylcysteine will remain uncertain unless a large well-designed multi-center trial is performed.
    Preview · Article · Nov 2004 · BMC Medicine
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    ABSTRACT: Contrast-induced nephropathy (CIN) is an important cause of declines in kidney function and is related to greater morbidity, health care costs, and mortality. Adenosine has been proposed to contribute to the pathophysiological process of CIN. We performed a systematic review and meta-analysis of theophylline, an adenosine antagonist, for the prevention of CIN. Studies were identified in all languages by search of MEDLINE (1966 through November 2003), EMBASE (1980 through week 44 [November] of 2003), and the Cochrane Controlled Clinical Trials Register (1996 through November 2003) databases and selected conference proceedings. We searched for randomized controlled trials comparing theophylline vs control in patients receiving radiocontrast media for angiography or computed tomography. Our primary outcome measures were the risk of CIN, the difference in serum creatinine levels between theophylline and control groups at 48 hours and need for dialysis. Nine randomized controlled trials involving 585 patients were identified and included for analysis. Theophylline protocols and definitions of CIN varied across studies. There was evidence of heterogeneity of results across trials (Q = 9.77; P = .08); therefore, pooled values require cautious interpretation. The overall pooled odds ratio (OR) using a conservative random-effects model was 0.40 (95% confidence interval [CI], 0.14 to 1.16; P = .09) indicating a trend toward reduction in the incidence of CIN with theophylline use. The pooled estimate for the difference in 48-hour serum creatinine levels between the theophylline and control groups was -0.17 mg/dL (95% CI, -0.28 to -0.06 mg/dL) (-15.2 micromol/L [95% CI, -24.6 to -5.7 micromol/L]) (P = .002), indicating that theophylline may be protective in CIN. The incidence of CIN requiring dialysis was uncommon and reported in only 1 case. Theophylline may reduce the incidence of CIN with an efficacy that is perhaps comparable to that reported in studies of N-acetylcysteine. However, findings are inconsistent across studies. A large, well-designed trial that incorporates the evaluation of clinically relevant outcomes is required to more adequately assess the role for theophylline in CIN prevention.
    No preview · Article · Jun 2005 · Archives of Internal Medicine