A meta-analysis of N-acetylcysteine in contrast-induced nephrotoxicity: unsupervised clustering to resolve heterogeneity

Gonzales, Denise A.; Norsworthy, Kelly J.; Kern, Steven J.; Banks, Steve; Sieving, Pamela C.; Star, Robert A.; Natanson, Charles; Danner, Robert L.

doi:10.1186/1741-7015-5-32

Cited by 137 publications

(78 citation statements)

References 103 publications

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“…NAC has mainly been studied in the setting of contrast nephropathy following the initial publication by Tepel et al [213] which provided the catalyst for the subsequent proliferation of similar studies [127, [213][214][215][216][217][218][219][220][221][222]. This subject continues to generate much research and has led to several meta-analysis [152, [223][224][225][226][227][228] (ESM Table S9). Most report a risk reduction, although study heterogeneity and positive reporting bias somewhat hinders definitive recommendations [229].…”

Section: Rationalementioning

confidence: 99%

Prevention of acute kidney injury and protection of renal function in the intensive care unit

et al. 2009

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Background: Acute renal failure on the intensive care unit is associated with significant mortality and morbidity. Objectives: To determine recommendations for the prevention of acute kidney injury (AKI), focusing on the role of potential preventative maneuvers including volume expansion, diuretics, use of inotropes, vasopressors/vasodilators, hormonal interventions, nutrition, and extracorporeal techniques. Method: A systematic search of the literature was performed for studies using these potential protective agents in adult patients at risk for acute renal failure/kidney injury between 1966 and 2009. The following clinical conditions were considered: major surgery, critical illness, sepsis, shock, and use of potentially nephrotoxic drugs and radiocontrast media. Where possible the following endpoints were extracted: creatinine clearance, glomerular filtration rate, increase in serum creatinine, urine output, and markers of tubular injury. Clinical endpoints included the need for renal replacement therapy, length of stay, and mortality. Studies are graded according to the international Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) group system Conclusions and recommendations: Several measures are recommended, though none carries grade 1A. We recommend prompt resuscitation of the circulation with special attention to providing adequate hydration whilst avoiding high-molecular-weight hydroxy-ethyl starch (HES) preparations, maintaining adequate blood Intensive Care Med (2010) 36:392-411 DOI 10.1007/s00134-009-1678 EXPERT PANEL pressure using vasopressors in vasodilatory shock. We suggest using vasopressors in vasodilatory hypotension, specific vasodilators under strict hemodynamic control, sodium bicarbonate for emergency procedures administering contrast media, and periprocedural hemofiltration in severe chronic renal insufficiency undergoing coronary intervention.

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Section: Rationalementioning

confidence: 99%

Prevention of acute kidney injury and protection of renal function in the intensive care unit

et al. 2009

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“…Daha sonraki çalışmalarda NAC oral düşük doz, oral yüksek doz ve intravenöz yollarla kullanılarak karşılaştırılmıştır. Ancak çalışmalarda ve metaanalizlerde çelişkili sonuçlar elde edilmiştir (6) .…”

Section: Yazışma Adresiunclassified

Contrast-Induced Nephropathy: Management by Antioxidant Therapy

Büyüklü¹

2017

Kosuyolu Heart Journal

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ÖZETGünümüzde görüntüleme ve girişimsel işlemlerin artış göstermesi ile birlikte kontrast madde kullanımı giderek artmıştır. Oksidatif stresin kontrast madde nefropatisi patofizyolojisinde önemli rolü vardır. Çeşitli önleyi-ci tedaviler ve yan etkisi daha az düşük osmolar kontrast maddelere rağmen, klinik pratikte tek önleyici tedavi intravenöz iztonik infüzyonudur. Bu yüzden yeni bir koruyucu tedaviye ihtiyaç vardır.Anahtar Kelimeler: Kontrast; kontrast madde nefropatisi; antioksidan tedavi; anjiyografi. Contrast-Induced Nephropathy: Management by Antioxidant Therapy ABSTRACTAt present, the number of imaging and interventional procedures using contrast agents is gradually increasing. Oxidative stress plays a significant role in its pathophysiology. Despite the use of various prophylactic therapies and low-osmolar contrast agents with lesser adverse effects, intravenous isotonic fluid infusion is the only method that has been proven to be effective in preventing contrast-induced nephropathy in clinic practice. Therefore, a novel kidney-protecting treatment model is required for contrast-induced nephropathy. Günümüzde görüntüleme ve girişimsel işlemlerin artış göstermesi ile birlikte kontrast madde (KM) kullanımı giderek artmıştır. Tartışılmaz faydalarının yanında yapılarındaki moleküler değişikliklere rağmen tüm KM'lerin hafiften şiddetli dereceye varan yan etkileri olabilmektedir. Bu yan etkilerden en önemlisi kontrast madde nefropatisi (KMN)'dir. KMN tanısı klinik pratikte serum kreatinin düzeyi (SKr) takibi ile konur. KM verildikten 48 saat sonra ölçülen SKr düzeyinde bazal değere göre %25'ten fazla artış olması veya 0.5 mg/dL'den fazla artış olması KMN tanısı açısından anlamlıdır. KMN hastanede gelişen akut böbrek yetersizliğinin üçüncü nedenidir (1) . Normal popü-lasyondaki insidansı %1-2 iken, diyabetik azotemi gibi risk faktörleri olan hastalarda bu oran %50'ye kadar çıkmaktadır (2) . KMN hastanede yatış süresini, morbiditeyi ve mortaliteyi arttıran bir durumdur.KMN patofizyolojisi tamamen belli olmamakla birlikte, bir çok faktör bu duruma yol açabilmektedir (3) .1. Direkt Toksik Etki: KM'ler filtre olurlar, fakat emilmezler. Bu nedenle tubül sistemi boyunca yüksek bir osmotik yük oluşur. Sonuç olarak tubüler hücrelerin intrasellüler transportu ve enerji metabolizması bozulur. "Osmotik nefrozis" diye adlandırılan bu durum tubüler hücre hasarına yol açar.2. Renal Mikrovasküler Hemodinamiksel Değişim: KM'nin intratubüler basınç artışına yol açması sonucu renal kan akımı azalır.3. Reperfüzyon ve ROS toksisitesi: Renal kan akımı azalması sonucu oluşan hipoksi, oksidatif stres yaparak, reaktif oksijen ürünleri (ROS) oluşumuna yol açar. ROS ise renal hasar oluşumuna katkıda bulunur.4. İnflamasyon Nedenli Toksisite: KM kompleman ve sitokin döngüsünü aktive ederek renal hasara katkıda bulunur.

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“…Because animal studies have indicated that NAC may protect the myocardium and preserve kidney function [128], it was expected to prevent CIN in humans. After the report by Tepel et al [65] on the effect of NAC (600 mg twice daily, orally) in preventing CIN, many RCTs and meta-analyses were conducted [129][130][131][132][133][134][135][136][137][138][139].…”

Section: Level Of Evidence: II Grade Of Recommendation: C2 Rationale mentioning

confidence: 99%

“…Although this meta-analysis concluded that NAC was more renoprotective than was saline hydration alone, the sample sizes of the studies analyzed and the quality of sample calculation methods used in the meta-analysis were questioned. In another meta-analysis of 22 RCTs, Gonzales et al [138] used a modified L'Abbé plot to divide the data into cluster 1 (18 studies, 2,445 patients) and cluster 2 (4 studies, 301 patients), and reported that cluster 1 studies showed no benefit, while cluster 2 studies indicated that NAC was highly beneficial. However, cluster 2 studies were published earlier, and were of lower quality as measured by Jadad scores (\3, three study characteristics combined) [138,139].…”

Section: Level Of Evidence: II Grade Of Recommendation: C2 Rationale mentioning

confidence: 99%

“…In another meta-analysis of 22 RCTs, Gonzales et al [138] used a modified L'Abbé plot to divide the data into cluster 1 (18 studies, 2,445 patients) and cluster 2 (4 studies, 301 patients), and reported that cluster 1 studies showed no benefit, while cluster 2 studies indicated that NAC was highly beneficial. However, cluster 2 studies were published earlier, and were of lower quality as measured by Jadad scores (\3, three study characteristics combined) [138,139]. At the present time, oral NAC treatment has not been demonstrated to be sufficiently effective in the prevention of CIN.…”

Section: Level Of Evidence: II Grade Of Recommendation: C2 Rationale mentioning

confidence: 99%

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Guidelines on the use of iodinated contrast media in patients with kidney disease 2012: digest version

et al. 2013

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A meta-analysis of N-acetylcysteine in contrast-induced nephrotoxicity: unsupervised clustering to resolve heterogeneity

Abstract: Background: Meta-analyses of N-acetylcysteine (NAC) for preventing contrast-induced nephrotoxicity (CIN) have led to disparate conclusions. Here we examine and attempt to resolve the heterogeneity evident among these trials.

Cited by 137 publications

References 103 publications

Prevention of acute kidney injury and protection of renal function in the intensive care unit

Prevention of acute kidney injury and protection of renal function in the intensive care unit

Contrast-Induced Nephropathy: Management by Antioxidant Therapy

Guidelines on the use of iodinated contrast media in patients with kidney disease 2012: digest version

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