{"id":1075,"date":"2012-08-01T00:00:07","date_gmt":"2012-08-01T07:00:07","guid":{"rendered":"http:\/\/rhochistj.org\/RhoChiPost\/?p=1075"},"modified":"2014-02-17T22:12:30","modified_gmt":"2014-02-18T05:12:30","slug":"role-n-acetylcysteine-contrast-induced-nephropathy","status":"publish","type":"post","link":"https:\/\/rhochistj.org\/RhoChiPost\/role-n-acetylcysteine-contrast-induced-nephropathy\/","title":{"rendered":"The Role of N-Acetylcysteine in Contrast Induced Nephropathy"},"content":{"rendered":"

By: Neal Shah, Co-Editor-In-Chief<\/span><\/p>\n

–<\/p>\n

Contrast dyes enhance imaging for computer tomography (CT), magnetic resonance (MR), and X-rays.1<\/sup> \u00a0Dyes usually consist of barium, iodine, or gadolinium, depending on the procedure.2<\/sup> \u00a0CT and X-ray scans often use iodine for systemic imaging and barium sulfate for GI imaging, whereas MR imaging primarily uses gadolinium.2<\/sup> \u00a0Gadolinium and iodine contrast dyes have renal elimination, and could lead to contrast-induced nephropathy (CIN), especially in patients with pre-existing renal impairment.3<\/sup><\/p>\n

The pathophysiology of CIN involves reduced blood flow to the kidneys (that causes ischemia), which leads to toxicity within tubular epithelial cells.3<\/sup> \u00a0The resulting reactive oxidative species (ROS) damage nephrons within the kidney and induce necrosis.3<\/sup> \u00a0CIN is defined as an abrupt increase in serum creatinine of 0.5 mg\/dL or a 25% increase from baseline levels 48 hours after injection of contrast media.4,5<\/sup> \u00a0Current strategies for managing CIN include: removal of nephrotoxic compounds, aggressive hydration, and administration of vasodilatory compounds (e.g.<\/i> theophylline) or anti-oxidant medications (e.g.<\/i> N-acetylcysteine [NAC]).3-5<\/sup> \u00a0NAC seemed a promising agent for mitigating CIN due to its low cost, multiple indications, and ease of use, but perspectives have changed.<\/p>\n

NAC is a modified amino acid used traditionally to reverse acetaminophen-induced hepatotoxicity and provide mucolytic activity in bronchial diseases.6<\/sup> \u00a0NAC is a precursor to the free radical scavenger, glutathione (GSH). \u00a0Normally, free radicals oxidize GSH, which reduces the damage caused by ROS to our cells.\u00a0 GSH is depleted upon major oxidative stress, and administration of NAC replenishes this depleted GSH content.7<\/sup> \u00a0Other uses of NAC include: increased ovulation and fertility in polycystic ovarian syndrome (PCOS) patients,8<\/sup> chemoprevention of certain cancers,9<\/sup> and oxaliplatin-induced\u00a0neuropathy.10<\/sup><\/p>\n

The efficacy of NAC in CIN is widely debated. \u00a0Data from 2011 and 2012 demonstrate that NAC is not efficacious in minimizing or preventing CIN. \u00a0Anderson et. al.<\/i>\u2019s MEDLINE meta-analysis concluded that papers published from 1990\u20142010 had no conclusive clinical evidence on NAC\u2019s safety or efficacy in the prevention of CIN.11<\/sup> \u00a0They found that while NAC improved serum creatinine levels, there was no improvement in overall renal function.11<\/sup> \u00a0A clinical trial in Brazil, published in September 2011, reported that in 2,038 patients with at least one risk factor for CIN, administration of NAC and placebo resulted in similar outcomes of CIN.12<\/sup> \u00a0The paper concluded that there were no significant risk reductions or enhanced outcomes of any kind with the administration of NAC.12<\/sup> \u00a0Tanaka et. al<\/i> reported that the administration of NAC in CIN had no significant differences in morbidity or mortality compared to placebo.13<\/sup> \u00a0Aligoglu et. al.<\/i> conducted a study measuring renal function with creatinine and cystatin C levels.14<\/sup> \u00a0Upon administration of oral NAC, there was no significant reduction in creatinine or cystatin C in patients with CIN treated with placebo or NAC.14<\/sup> \u00a0Jaffery et. al. <\/i>conducted a study in 398 patients, defining CIN as an increase in creatinine concentration \u2265 25% above the baseline level within 72 hours of the administration of intravenous\u00a0contrast.15<\/sup> \u00a0They reported that high-dose intravenous NAC failed to reduce the incidence of CIN.15<\/sup> \u00a0Aslanger et. al.<\/i> examined NAC\u2019s prophylactic utility in CIN with a study of 312 patients, but found that intrarenal and intravenous NAC had no significant benefit compared to placebo.16<\/sup><\/p>\n

The most conclusive evidence against NAC\u2019s efficacy in CIN came from a paper by Gurm et. al.<\/i> published in January 2012. \u00a0A retrospective analysis of NAC use in 10,574 out of 90,578 patients who underwent percutaneous coronary intervention (PCI) demonstrated no statistical significance between NAC treated patients and non-treated patients that developed CIN.17<\/sup> \u00a0The authors concluded that there was no clinical improvement associated with NAC use in CIN.17<\/sup><\/p>\n

Overall, while NAC remains efficacious in exerting mucolytic effects in bronchial diseases and assisting in decreasing acetaminophen-induced hepatotoxicity, overwhelming clinical evidence has reported against using NAC in CIN.<\/p>\n

SOURCES:<\/span><\/b><\/p>\n

    \n
  1. CT Scan.\u00a0 Available at: http:\/\/www.nlm.nih.gov\/medlineplus\/ency\/article\/003330.htm.<\/a>\u00a0 Accessed June 24, 2012.<\/li>\n
  2. Contrast Materials.\u00a0 Available at: http:\/\/www.radiologyinfo.org\/en\/safety\/index.cfm?pg=sfty_contrast.<\/a>\u00a0 Accessed June 24, 2012.<\/li>\n
  3. Rudnick M, Kesselheim A, Goldfarb S. Contrast-induced nephropathy:\u00a0 How it develops, how to prevent it.\u00a0 Cleveland Clinic Journal Of Medicine.\u00a0 Volume 73.\u00a0 January 2006.<\/li>\n
  4. Wong GTC and Irwin MG.\u00a0 Contrast-induced nephropathy.\u00a0 Br J Anaesth<\/i>.\u00a0 2007;99(4):474\u201483.<\/li>\n
  5. McCullough PA, Soman SS. Contrast-induced nephropathy.\u00a0 Crit Care Clin<\/i>.\u00a0 2005;21(2):261\u201480.<\/li>\n
  6. N-Acetylcysteine.\u00a0 Available at: http:\/\/www.mskcc.org\/cancer-care\/herb\/n-acetylcysteine.<\/a>\u00a0 Accessed June 24, 2012.<\/li>\n
  7. Tepel M.\u00a0 N-Acetylcysteine in the prevention of ototoxicity.\u00a0 Kidney Int.<\/i> 2007 Aug;72(3):231-2.<\/li>\n
  8. Salehpour S, Akbari Sene A, Saharkhiz N, et. al.<\/i> N-acetylcysteine as an adjuvant to clomiphene citrate for successful induction of ovulation in infertile patients with polycystic ovary syndrome.\u00a0 J Obstet Gynaecol Res.<\/i> 2012.<\/li>\n
  9. Estensen RD, Levy M, Klopp SJ et. al.<\/i> N-acetylcysteine suppression of the proliferative index in the colon of patients with previous adenomatous colonic polyps.\u00a0 Cancer Lett.<\/i>\u00a0 1999;147(1\u20142):109\u201414.<\/li>\n
  10. Lin PC, Lee MY, Wang WS et. al.<\/i> N-acetylcysteine has neuroprotective effects against oxaliplatin-based adjuvant chemotherapy in colon cancer patients: preliminary data.\u00a0 Support Care Cancer.<\/i>\u00a0 2006;14(5):484\u20147.<\/li>\n
  11. Anderson SM, Park ZH, Patel RV.\u00a0 Intravenous N-acetylcysteine in the prevention of contrast media-induced nephropathy.\u00a0 Ann Pharmacother.<\/i>\u00a0 2011;45(1):101\u20147.<\/li>\n
  12. Berwanger O, Cavalcanti AB, Sousa AG et. al.<\/i> Acetylcysteine for prevention of renal outcomes in patients undergoing coronary and peripheral vascular angiography: main results from the randomized Acetylcysteine for Contrast-induced nephropathy Trial (ACT).\u00a0 Circulation.<\/i>\u00a0 2011;124(11):1250\u20149.<\/li>\n
  13. Tanaka A, Suzuki Y, Suzuki N et. al.<\/i>\u00a0 Does N-acetylcysteine reduce the incidence of contrast-induced nephropathy and clinical events in patients undergoing primary angioplasty for acute myocardial infarction?\u00a0 Intern Med. <\/i>2011;50(7):673\u20147.<\/li>\n
  14. Alioglu E, Saygi S, Turk U et. al.<\/i> N-Acetylcysteine in Preventing Contrast-Induced Nephropathy Assessed by Cystatin C. Cardiovasc Ther.<\/i>\u00a0 2011.<\/li>\n
  15. Jaffery Z, Verma A, White CJ, et. al.<\/i>\u00a0 A randomized trial of intravenous n-acetylcysteine to prevent contrast induced nephropathy in acute coronary syndromes.\u00a0 Catheter Cardiovasc Interv.<\/i> 2012 May 1;79(6):921-6.<\/li>\n
  16. Aslanger E, Uslu B, Akdeniz C et. al.<\/i> Intrarenal application of N-acetylcysteine for the prevention of contrast medium-induced nephropathy in primary angioplasty.\u00a0 Coron Artery Dis<\/i>. 2012;23(4):265\u201470.<\/li>\n
  17. Gurm HS, Smith DE, Berwanger O et. al.<\/i> Contemporary use and effectiveness of N-acetylcysteine in preventing contrast-induced nephropathy among patients undergoing percutaneous coronary intervention.\u00a0 JACC Cardiovasc Interv.<\/i>\u00a0 2012;5(1):98\u2014104.<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    By: Neal Shah, Co-Editor-In-Chief – Contrast dyes enhance imaging for computer tomography (CT), magnetic resonance (MR), and X-rays.1 \u00a0Dyes usually consist of barium, iodine, or gadolinium, depending on the procedure.2 \u00a0CT and X-ray scans often use iodine for systemic imaging and barium sulfate for GI imaging, whereas MR imaging primarily uses gadolinium.2 \u00a0Gadolinium and iodine…<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[7],"tags":[46,668,1822,343,22,40,974,2246,163,2227,29,420,314,407,1646,93,96,2235,725,363,968,1625,657,212,1820,55,36,99,1666,21,539,149,17,1061],"class_list":["post-1075","post","type-post","status-publish","format-standard","hentry","category-clinical","tag-acetaminophen","tag-acid","tag-against","tag-and","tag-blood","tag-cancer","tag-citrate","tag-clinic","tag-dose","tag-ebola-virus-disease","tag-editor","tag-factor","tag-for","tag-injection","tag-intravenous","tag-january","tag-june","tag-kidney","tag-mg","tag-of","tag-one","tag-or","tag-oral","tag-paper","tag-reduction","tag-renal","tag-risk","tag-september","tag-sm","tag-study","tag-sulfate","tag-syndrome","tag-trial","tag-with"],"views":2508,"_links":{"self":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/posts\/1075","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/comments?post=1075"}],"version-history":[{"count":0,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/posts\/1075\/revisions"}],"wp:attachment":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/media?parent=1075"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/categories?post=1075"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/tags?post=1075"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}