Acetylcysteine for prevention of contrast-induced nephropathy after intravascular angiography: a systematic review and meta-analysis

Sean M Bagshaw, William A Ghali, Sean M Bagshaw, William A Ghali

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Figures

Figure 1
Figure 1
Flow diagram of study selection process.
Figure 2
Figure 2
Forest plot of odds ratios for development of contrast-induced nephropathy from 14 trials.
Figure 3
Figure 3
Forest plot of differences in serum creatinine between acetylcysteine and control at 48 h after contrast media administration from eight trials.
Figure 4
Figure 4
Evidence of publication bias by Funnel plot. Funnel plot asymmetry is demonstrated by evidence of a cluster of small studies with low-protective odds ratio and the paucity of small negative studies in the lower right of the funnel plot.

References

    1. Hou SH, Bushinsky DA, Wish JB, Cohen JJ, Harrington JT. Hospital-acquired renal insufficiency: A prospective study. American Journal of Medicine. 1983;74:243–248. doi: 10.1016/0002-9343(83)90618-6.
    1. Shusterman N, Strom B, Murray T. Risk factors and outcome of hospital-acquired acute renal failure. American Journal of Medicine. 1987;83:65–71. doi: 10.1016/0002-9343(87)90498-0.
    1. Murphy SW, Barrett BJ, Parfrey PS. Contrast nephropathy. Journal of the American Society of Nephrology. 2000;11:177–182.
    1. Levy EM, Viscoli CM, Horwitz RI. The effect of acute renal failure on mortality. JAMA. 1996;275:1489–1494.
    1. Powe N, Moore R, Steinberg E. Adverse reactions to contrast media: Factors that determine the cost of treatment. AJR. 1993;161:1089–1095.
    1. Gruberg L, Mintz GS, Mehran R, Dangas G, Lansky AJ, Kent KM, Pichard A, Satler LF, Leon MB. The prognostic implications of further renal function deterioration within 48 h of interventional coronary procedures in patients with pre-existent chronic renal insufficiency. Journal of the American College of Cardiology. 2000;36:1542–1548. doi: 10.1016/S0735-1097(00)00917-7.
    1. Davidson C, Hlatky M, Morris K. Cardiovascular and renal toxicity of a nonionic radiocontrast agent after cardiac catheterization. Annals of Internal Medicine. 1989;110:119.
    1. Rich MW, Crecelius CA. Incidence, risk factors, and clinical course of acute renal insufficiency after cardiac catheterization in patients 70 years of age or older. Archives of Internal Medicine. 1990;150:1237–1242. doi: 10.1001/archinte.150.6.1237.
    1. Bakris GZ, Lass N, Gager A. Radiocontrast medium-induced declines in renal function: A role for oxygen free radicals. Am J Physiol. 1990;258:F115–F120.
    1. Bakris G, Lass N, Glock D. Renal hemodynamics in radiocontrast medium-induced renal dysfunction. Kidney International. 1999;56:206–210. doi: 10.1046/j.1523-1755.1999.00528.x.
    1. Heyman S, Reichman J, Brezis M. Pathophysiology of radiocontrast nephropathy: a role for medullary hypoxia. Invest Radiol. 1999;34:685–691. doi: 10.1097/00004424-199911000-00004.
    1. DiMari J, Megyesi J, Udvarhelyi N, Price P, Davis R, Safirstein R. N-acetyl cysteine ameliorates ischemic renal failure. Am J Physiol. 1997;272:F292–F298.
    1. Lefebvre C, Clarke M. Identifying randomized trials. In: Egger M, Smith G, Altman D, editor. In Systematic Reviews in Health Care. Second. London: BMJ Publications; 2001. pp. 69–86.
    1. Robinson K, Hinegardner P, Lansing P. Development of an optimal search strategy for the retrieval of controlled trials using Pubmed. In Proc 6th Int Cochrane Collouium. 1998. poster B13.
    1. Dickersin K, Scherer R, Lefebvre C. Identifying relevant studies for systematic reviews. BMJ. 1994;309:1286–1291.
    1. Jadad A, Moore R, Carrol D, Jenkinson C, Reynolds J, Gavaghan D, McQuay H. Assessing the quality of reports of randomized clinical trials: Is blinding necessary? Control Clin Trials. 1996;17:1–12. doi: 10.1016/0197-2456(95)00134-4.
    1. Juni P, Altman D, Egger M. Assessing the quality of randomised controlled trials. In: Egger M, Smith G, Altman D, editor. Systematic Reviews in Health Care. Second. London: BMJ Publishing; 2001. pp. 87–108.
    1. Shea B, Dube C, Moher D. Assessing the quality of reports of systematic reviews: the QUOROM statement compared to other tools. In: Egger M, Smith G, Altman D, editor. Systematic Reviews in Health Care. Second. London: BMJ Publishing; 2001. pp. 122–139.
    1. Thompson S. Why sources of heterogeneity in meta-analysis should be investigated. BMJ. 1994;309:1351–1355.
    1. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–188. doi: 10.1016/0197-2456(86)90046-2.
    1. Senn S, Walter S, Olkin I. Odds ratios revisited. Evidence-Based Med. 1998;3:71.
    1. Thompson S, Sharp S. Explaining heterogeneity in meta-analysis: a comparison of methods. Stat Med. 1999;18:2693–2708. doi: 10.1002/(SICI)1097-0258(19991030)18:20<2693::AID-SIM235>;2-M.
    1. Dear K, Begg C. An approach to assessing publication bias prior to performing a meta-analysis. Stat Sci. 1992;7:237–245.
    1. Egger M, Davey S, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–634.
    1. Allaqaband S, Tumuluri R, Malik A. Prospective randomized study of N-acetylcysteine, fenoldopam, and saline for prevention of radiocontrast-induced nephropathy. Catheter Cardiovasc Interv. 2002;57:279–283. doi: 10.1002/ccd.10323.
    1. Baker C, Wragg A, Kuna S, DePalma R, Baker L. A rapid protocol for the prevention of contrast-inducted renal dysfunction: The RAPPID Study. Journal of the American College of Cardiology. 2003;41:2114–2118. doi: 10.1016/S0735-1097(03)00487-X.
    1. Briguori C, Manganelli F, Scarpato P, Elia PP, Golia B. Acetylcysteine and contrast agent-associated nephrotoxicity. Journal of the American College of Cardiology. 2002;40:298–303. doi: 10.1016/S0735-1097(02)01958-7.
    1. Diaz-Sandoval LJ, Kosowsky BD, Losordo DW. Acetylcysteine to prevent angiography-related renal tissue injury (The APART Trial) American Journal of Cardiology. 2002;89:356–358. doi: 10.1016/S0002-9149(01)02243-3.
    1. Durham JD, Caputo C, Dokko J, Zaharakis T, Pahlavan M. A randomized controlled trial of N-acetylcysteine to prevent contrast nephropathy in cardiac angiography. Kidney International. 2002;62:2202–2207. doi: 10.1046/j.1523-1755.2002.00673.x.
    1. Efrati S, Dishy V, Averbukh M, Blatt A, Krakover R, Weisgarten J, Morrow J, Stein M, Golik A. The effect of N-acetylcysteine on renal function, nitric oxide, and oxidative stress after angiography. Kidney International. 2003;64:2182–2187. doi: 10.1046/j.1523-1755.2003.00322.x.
    1. Fung J, Szeto C, Chan W, Kum L, Chan A, Wong J, Wu E, Yip G, Chan J, Yu C, Woo K, Sanderson J. Effect of N-acetylcysteine for prevention of contrast nephropathy in patients with moderate to severe renal insufficiency: a randomized trial. American Journal of Kidney Diseases. 2004;43:801–808. doi: 10.1053/j.ajkd.2004.01.010.
    1. Goldenberg I, Schechter M, Matetzki S, Jonas M, Adam M, Pres H, Elian D, Agranat O, Schwammenthal E, Guetta V. Oral acetylcysteine as an adjunct to saline hydration for prevention of contrast-induced nephropathy following coronary angiography. Eur Heart J. 2004;25:212–218. doi: 10.1016/j.ehj.2003.11.011.
    1. Kay J, Chow WH, Chan TM, Lo SK, Kwok OH, Yip A. Acetylcysteine for prevention of acute deterioration of renal function following elective coronary angiography and intervention: a randomized controlled trial. JAMA. 2003;289:553–558.
    1. Kefer J, Hanet C, Boitte S, Wilmotte L, De Kock M. Acetylcysteine, coronary procedure and prevention of contrast-induced worsening of renal function: which benefit for which patients? Acta Cardiol. 2003;58:555–560.
    1. MacNeill B, Harding S, Bazari H, Patton K, Colon-Hernadez P, de Joseph D, Jang I. Prophylaxis of contrast-induced nephropathy in patients undergoing coronary angiography. Catheter Cardiovasc Interv. 2003;60:458–461. doi: 10.1002/ccd.10684.
    1. Oldemeyer JB, Biddle P, Wurdeman R, Mooss A, Cichowski E, Hilleman D. Acetylcysteine in the prevention of contrast-induced nephropathy after coronary angiography. Am J Heart. 2003;146:e23.
    1. Shyu K-G, Cheng J-J, Kuan P. Acetylcysteine protects against acute renal damage in patients with abnormal renal function undergoing a coronary procedure. Journal of the American College of Cardiology. 2002;40:1383–1388. doi: 10.1016/S0735-1097(02)02308-2.
    1. Vallero A, Cesano G, Pozzato M, Garbo R, Minelli M, Quarello F, Formica M. Contrast nephropathy in cardiac procedures: No advantages with prophylactic use of N-acetylcysteine (NAC) Giornale Italiano di Nefrologia. 2002;19:529–533.
    1. Cook D, Guyatt G, Ryan G, Clifton J, Buckingham L, Willan A, McIlroy W, Oxman A. Should unpublished data be included in meta-analyses? Current convictions and controversies. JAMA. 1993;269:2749–2753.
    1. Birck R, Krzossok S, Makowetz F, Schnulle P, van der Woude F, Braun C. Acetylcysteine for prevention of contrast nephropathy: meta-analysis. Lancet. 2003;362:598–603. doi: 10.1016/S0140-6736(03)14189-X.
    1. Isenbarger D, Kent S, O'Malley P. Meta-analysis of randomized clinical trials on the usefulness of acetycysteine for prevention of contrast nephropathy. Am J Card. 2003;92:1454–1458. doi: 10.1016/j.amjcard.2003.08.059.
    1. Alonso A, Lau J, Jaber B, Weintraub A, Sarnak M. Prevention of radiocontrast nephropathy with N-acetylcysteine in patients with chronic kidney disease: a meta-analysis of randomized, controlled trials. American Journal of Kidney Diseases. 2004;43:1–9. doi: 10.1053/j.ajkd.2003.09.009.
    1. Faddy S. Significant statistical heterogeneity in a meta-analysis of the usefulness of acetylcysteine for prevention of contrast nephropathy. Am J Cardiol. 2004;94:414. doi: 10.1016/j.amjcard.2004.02.079.
    1. Pannu N, Manns B, Lee H, Tonelli M. Systematic review of the impact of N-acetylcysteine on contrast nephropathy. Kidney International. 2004;65:1366–1374. doi: 10.1111/j.1523-1755.2004.00516.x.
    1. Kshirsagar A, Poole C, Mottl A, Shoham D, Francechini N, Tudor G, Agrawal M. N-acetylcysteine for the prevention of radiocontrast induced nephropathy: A meta-analysis of prospective controlled trials. Journal of the American Society of Nephrology. 2004;15:761–769. doi: 10.1097/01.ASN.0000116241.47678.49.
    1. Teo KK, Yusuf S, Collins R, Held PH, Peto R. Effects of intravenous magnesium in suspected acute myocardial infarction: overview of randomized trials. BMJ. 1991;303:1499–1503.
    1. Horner S. Efficacy of intravenous magnesium in acute myocardial infarction in reducing arrhythmias and mortality: Meta-analysis of magnesium in acute myocardial infarction. Circulation. 1992;86:774–779.
    1. Yusuf S, Koon T, Woods K. Intravenous magnesium in acute myocardial infarction. An effective, safe, simple, and inexpensive intervention. Circulation. 1993;87:2043–2046.
    1. Group I-FISoISC. ISIS-4: A randomized factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58 050 patients with suspected acute myocardial infarction. Lancet. 1995;345:669–685. doi: 10.1016/S0140-6736(95)90865-X.
    1. Baxter G, Sumeray M, Walker J. Infarct size and magnesium: insights into LIMIT-2 and ISI-4 from experimental studies. Lancet. 1996;348:1424–1426. doi: 10.1016/S0140-6736(96)07281-9.
    1. Investigators TMiCMT Early administration of intravenous magnesium to high-risk patients with acute myocardial infarction in the Magnesium in Coronaries (MAGIC) Trial: a randomized controlled trial. Lancet. 2002;360:1189–1196. doi: 10.1016/S0140-6736(02)11278-5.
    1. Egger M, Davey Smith G. Misleading meta-analysis. BMJ. 1995;310:352–354.
    1. Guitterez N, Diaz A, Timmis G, O'Neill WW, Stevens MA, Sandberg K, McCullough PA. Determinants of serum creatinine trajectory in acute contrast nephropathy. J Interv Cardiol. 2002;15:349–354.
    1. Hemmelgarn BR, Ghali WA, Quan H, Brant R, Norris CM. Poor long-term survival after coronary angiography in patients with renal insufficiency. American Journal of Kidney Diseases. 2001;37:64–72.
    1. Merten G, Burgess W, Gray L, Holleman J, Roush T, Kowalchuk G, Bersin R, Moore A, Simonton C, Rittase R, Norton H, Kennedy T. Prevention of contrast-induced nephropathy with sodium bicarbonate. JAMA. 2004;291:2328–2334.
    1. Stone G, Mc Cullough P, Tumlin J, Lepor N, Madyoon H, Murray P, Wang A, Chu A, Schaer G, Stevens M, Wilensky R, O'Neill W. Fenoldopam mesylate for the prevention of contrast-induced nephropathy: A randomized controlled trial. JAMA. 2003;290:2284–2291.
    1. Briguori C, Colombo A, Airoldi F, Violante A, Castelli A, Balestrieri P, Elia PP, Golia B, Lepore S, Riviezzo G, Scarpato P, Librera M, Focaccio A, Ricciardelli B. N-acetylcysteine versus fenoldopam mesylate to prevent contrast agent-associated nephrotoxicity. Journal of the American College of Cardiology. 2004;44:762–765. doi: 10.1016/j.jacc.2004.04.052.
    1. Bagshaw S, Culleton B. Acetylcysteine for the prevention of contrast nephropathy. JAMA. 2003;289:2795.

Source: PubMed

3
Subscribe