Prevention of contrast-induced nephropathy in vascular patients undergoing angiography: a randomized controlled trial of intravenous N-acetylcysteine

OBJECTIVE(S): Apart from proper hydration, only oral N-acetylcysteine (NAC) has shown efficacy in reducing radiographic contrast media (RCM)-induced acute renal failure, though its benefit has been challenged. We investigated the effect of intravenous (i.v.) NAC on renal function in patients with vascular disease receiving RCM for angiography. METHODS: Single-center, randomized, double-blind, placebo-controlled trial. Based on a previous study, a trial with 44 patients each in placebo and treatment arms would give at least 80% power to show a statistically significant difference at the 5% level. Vascular patients undergoing angiography were consented and segregated into those whose serum creatinine (SC) level was normal or raised (men >1.32 mg/dl; women >1.07 mg/dL). All patients received 500 mL i.v. normal saline 6 to 12 hours prior to and then after angiography. Groups with normal SC and raised SC were randomly assigned to either 1 g of NAC with normal saline before and after angiography or nothing (placebo). Main outcome measures were change in SC and creatinine clearance (CrCl) as measured 1, 2, and 7 days postangiography (with comparison between active and placebo groups using unpaired t test) and incidence of acute renal decline (>25% or 0.5 mg/dL rise in SC) at 48 hours (with comparison between active and placebo using the Fisher exact test). RESULTS: Forty-six patients received NAC (29 normal SC, 17 raised SC), and 48 received placebo (27 normal SC, 21 raised SC). There was no significant difference in postangiography SC or CrCl at any of the time points measured between NAC and placebo in patients with either normal or raised SC. In the raised SC group, 3 patients from both the NAC and placebo groups suffered acute renal declines. Importantly, at 48 hours, the impaired SC group had a significant reduction in CrCl (-14% +/- 41% vs +18% +/- 58%: P = .0142) and a significant rise in SC (+7.0 +/- 25% vs -1.6% +/- 10%; P = .0246) when compared with the normal SC group. CONCLUSIONS: NAC (i.v. at 1 g) precontrast and postcontrast does not confer any benefit in preventing RCM-induced nephropathy in vascular patients. Patients with pre-existing raised SC have an increased risk of renal impairment as defined by a fall in CrCl and a rise in SC post-RCM when compared with patients with normal SC who appear to benefit from hydration.     

Pentoxifylline for the prevention of contrast-induced nephropathy in diabetic patients undergoing angioplasty: a randomized controlled trial

International Urology and Nephrology - Contrast-induced nephropathy (CIN) is one of the most important complications of contrast media. We aimed to evaluate the preventive effects of pentoxifylline...     

口服和静脉给予N-乙酰半胱氨酸预防对比剂肾病的疗效比较

目的比较口服与静脉注射途径给药对N-乙酰半胱氨酸(N-acetylcysteine,NAC)预防轻度肾功能异常患者接受增强电子计算机断层扫描成像(computed tomography,CT)后对比剂肾病(contrast-induced nephropathy,CIN)的疗效。方法选择2013年7月至2015年1月武汉大学中南医院接受增强CT检查且肾功能轻度受损的97例患者,按照随机数字表法将患者分为口服NAC组(48例)及静脉注射NAC组(49例);其中口服NAC组患者于增强CT检查前1 d开始口服NAC泡腾片(600mg/片)1 200 mg,2次/d,共2 d,并于CT检查前1 h静脉注射10%葡萄糖注射液250 ml;静脉注射NAC组患者增强CT检查前1 h及检查后第2天各静脉注射NAC 4 g+10%葡萄糖注射液250 ml。2组患者均于CT检查后均立即静脉注射0.9%氯化钠注射液500 ml,并自由饮水。观察2组患者使用对比剂(碘帕醇)前与使用后48 h血肌酐(SCr)、血清胱抑素C(Cystatin C,Cys C)及估算肾小球滤过率(estimated glomerular filtration rate,eGFR)的变化,并统计2组患者CIN发生率。结果口服NAC组患者SCr及CysC水平较增强CT检查前升高(P0.05),eGFR水平较CT检查前降低(P0.05);静脉注射NAC组患者增强CT检查前后SCr、Cys C及eGFR水平差异无统计学意义(P0.05);口服NAC组患者增强CT检查后SCr及Cys C水平较静脉注射NAC组升高(P0.05),eGFR水平较静脉注射NAC组降低(P0.05);口服NAC组有8例患者接受增强CT检查后48 h的SCr明显升高。静脉注射NAC组有1例CIN发生,经校正的四格表X~2检验,差异有统计学意义(X~2=4.547,P=0.033)。结论静脉注射NAC预防CIN的效果较口服给药效果好,临床上对于轻度肾功能不全的患者增强CT检查前、后应静脉途径给予NAC治疗以预防CIN的发生。     

N-acetylcysteine for the prevention of radiocontrast induced nephropathy: a meta-analysis of prospective controlled trials

N-acetylcysteine has been recommended for patients with renal insufficiency who are to receive radiocontrast media. However, trials of oral N-acetylcysteine for the prevention of radiocontrast-induced nephropathy have yielded inconsistent results. A systematic review of patient and study characteristics was undertaken to discover possible explanations of the inconsistencies. The databases MEDLINE, EMBASE, and CENTRAL (1966 to March 2003) were searched in all languages, and conference proceedings from several professional societies from the years 1999 to 2003 were also searched. Only prospective controlled trials of oral N-acetylcysteine were included. Risk difference estimates and 95% confidence intervals were calculated. The estimates were examined for evidence of publication bias and heterogeneity. Stratified and meta-regression analyses were used to compare estimates by study and patient characteristics. Identified were 16 studies, 15 published and 1 unpublished. There was no evidence of publication bias, but there was substantial evidence of heterogeneity, thus precluding reliance on a meaningful summary effect estimate. Meta-regression identified several patient and study characteristics, with some evidence of association with study-specific estimates. None of these characteristics, however, formed subsets of studies with results that were homogeneous enough to aggregate. Research on N-acetylcysteine and the incidence of radiocontrast nephropathy is too inconsistent at present to warrant a conclusion on efficacy or a recommendation for its routine use. Identified patient and study characteristics may be responsible for some, but not all, of this inconsistency. A large, randomized, placebo-controlled trial, a pooled analysis of patient-level data, or both may resolve this issue.     

Immunosuppressive treatments for immunoglobulin A nephropathy: a meta-analysis of randomized controlled trials

Immunoglobulin A (IgA) nephropathy is a worldwide disease that causes end-stage kidney disease (ESRD) in up to 15-20% of affected patients within 10 years from the apparent onset of disease and in up to 30-40% of individuals within 20 years from diagnosis. No specific treatment has been established and there is wide variation in current practice. This systematic review evaluates the use of immunosuppressive agents to treat patients with IgA nephropathy. The Cochrane Renal Group Specialized Register, Cochrane Controlled Trial Registry, MEDLINE, EMBASE and article reference lists were searched for randomized or quasi randomized trials. Two independent reviewers assessed studies for inclusion criteria (biopsy proven IgA nephropathy, randomized trial, use of immunosuppressive agents) and extracted data regarding the effects of immunosuppressive agents on ESRD, doubling of serum creatinine, glomerular filtration rate, urinary protein excretion and side-effects. Data were analysed with a random effects model. The published trials were few (13 trials, 623 patients) and were generally of poor quality. Compared with placebo, steroids were associated with a lower risk of progression to ESRD (six trials, 341 patients, RR 0.44, 95% CI 0.25-0.80) and lower end-of-trial proteinuria (six trials, 263 patients, weighted mean difference (WMD) -0.49 g/day, 95% CI -0.25 to -0.72). Treatment with alkylating agents significantly reduced end of treatment proteinuria (two trials, 122 patients, WMD -0.94, 95% CI -0.46 to -1.43). Although the optimal management of patients with IgA nephropathy remains uncertain because of limitations with the existing published data, immunosuppressive agents are a promising strategy and should be investigated further.     

The efficacy of probucol combined with hydration in preventing contrast-induced nephropathy in patients with coronary heart disease undergoing percutaneous coronary intervention: a multicenter,prospective, randomized controlled study

Purpose

To investigate the preventive effect of probucol combined with hydration on contrast-induced nephropathy (CIN) in patients with coronary heart disease undergoing percutaneous coronary intervention (PCI).

Methods

A total of 641 patients undergoing PCI were randomly assigned to either a probucol group (probucol 500 mg twice daily and hydration; n = 321) or a control group (hydration only; n = 320). The primary endpoint was the incidence of CIN, defined as an increase in serum creatinine (Scr) by ≥ 44.2 μmol/L or ≥ 25% within 72 h after the administration of contrast agent. Secondary endpoints were changes in Scr, cystatin-C (Cys-C), creatinine clearance rate (Ccr), C-reactive protein (CRP), superoxide dismutase (SOD), and glutathione (GSH) within 72 h, and major adverse events during hospitalization or the 14-day follow-up period.

Results

The incidence of CIN was 4.0% (13/321) in the probucol group and 10.9% (35/320) in the control group. The probucol group had lower Cys-C and higher Ccr at 48 and 72 h after PCI compared with the control group. At 48 and 72 h following the operation, Cys-C and CRP were lower in the probucol group compared with the control group, but Ccr, SOD, and GSH were higher. There were no differences in the incidence of major adverse events during hospitalization or the 14-day follow-up between the groups. Multivariate logistic regression analysis showed that probucol was an independent protective factor for CIN.

Conclusions

Probucol combined with hydration more effectively decreased the incidence of CIN in patients with coronary heart disease undergoing PCI compared with hydration alone.

     

N-乙酰半胱胺酸对高龄患者对比剂肾病的预防作用

目的 探讨N-乙酰半胱氨酸（N-acetylcysteine,NAC）对行增强CT检查的高龄患者对比剂肾病（contrast-induced nephropathy,CIN）的预防作用.方法 将行增强CT检查的高龄患者56例,采用随机数字表法随机分为NAC组28例、对照组28例.NAC组于增强CT检查前12 h、6 h,检查后6 h、12 h分别口服NAC泡腾片1 200 mg,2组均给予水化治疗,比较CT前后2组患者血肌酐和估算肾小球滤过率（estimated glomerular filtration rate,eGFR）变化,以及2组患者CIN发生率.结果 NAC组与对照组比较,增强CT检查后48 h,2组患者SCr水平均高于CT检查前（P＜0.01）,eGFR水平均低于CT检查前（P＜0.01）;检查前后NAC组SCr升高幅度与对照组比较差异无统计学意义（P＞0.05）,检查前、后NAC组eGFR下降幅度小于对照组,差异有统计学意义（P＜0.05）.NAC组无CIN发生,对照组仅有1例在行CT检查后SCr明显升高（SCr升高19.4 μmol/L,上升幅度28%）,但无临床意义,2组经校正的四格表χ2检验,差异无统计学意义（P＞0.05）.结论 NAC联合水化治疗对患者行增强CT所致CIN的预防作用与单纯水化治疗相当.说明大剂量NAC对对比剂引起的肾损害具有一定的防治作用.     

Comparative efficacy of pharmacological interventions for contrast-induced nephropathy prevention after coronary angiography: a network meta-analysis from randomized trials

Background

Contrast-induced nephropathy (CIN) is the major complication related to contrast media administration in patients after coronary angiography (CAG). However, inconsistent results have been published in the literature regarding the effects of pharmacological drugs on CIN prevention. We conducted a network meta-analysis to evaluate the relative efficacy of pharmacological interventions for the prevention of CIN.

Methods

We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to July 2017. We included any randomized controlled trials of eleven pharmacological interventions that reported the prevention of CIN.

Results

We identified 3850 records through database searches, of which 107 studies comprising 21,450 participants were finally identified. Compared with intravenous saline, intravenous saline plus pharmacological drugs including statin [relative risk (RR) 0.57; 95% credibility interval (CrI) 0.39 to 0.83], N-acetylcysteine (NAC) (RR 0.84; 95% CrI, 0.71 to 0.98), vitamin and its analogues (RR 0.66; 95% CrI 0.45 to 0.97), brain natriuretic peptide (BNP) and its analogues (RR 0.46; 95% CrI 0.30 to 0.70), prostaglandin analogues (RR 0.37; 95% CrI 0.18 to 0.76), NAC plus sodium bicarbonate (SB) (RR 0.60; 95% CrI 0.39 to 0.90), and statin plus NAC (RR 0.39; 95% CrI 0.21 to 0.70), have helped to reduce the incidence of CIN in patients after CAG. The top four ranked treatments were statin plus NAC, BNP and its analogues, statin, and vitamin and its analogues, respectively. NAC plus intravenous saline was associated with lower incidence of short-term all-cause mortality than intravenous saline alone (RR 0.62; 95% CI, 0.40 to 0.96; P = 0.03). However, no evidence indicated that any of the pharmacological drugs were associated with a reduced requirement for dialysis and major adverse cardiac and cerebrovascular events (MACCE).

Conclusions

Statin plus NAC plus intravenous saline seems to be the most effective treatment for the prevention of CIN in patients after CAG. NAC plus intravenous saline may have a protective role against short-term all-cause mortality. However, none of these drugs has effectively decreased the requirement for dialysis and MACCE.

     

N-acetylcysteine for the prevention of contrast-induced nephropathy in patients with pre-existing renal insufficiency or diabetes: a systematic review and meta-analysis

Abstract

Purpose: To identify benefit of N-acetylcysteine (NAC) on patients with pre-existing renal insufficiency or diabetes. Background: NAC administration is a common method for prevention of contrast-induced nephropathy (CIN). Nevertheless, its benefit on patients with pre-existing renal insufficiency or diabetes remains uncertain and controversial. Methods: Randomized controlled trials (RCTs) to evaluate the efficacy of NAC for the prevention of CIN in patients with pre-existing renal insufficiency or diabetes were searched from the databases of MEDLINE, EMBASE, and Cochrane library. Pooled odds ratio (OR) with 95% confidence interval (95% CI) were calculated using fixed-effects model by the Mantel–Haenszel test. Results: Twenty RCTs involving 3466 subjects (1756 assigned to NAC and 1710 assigned to the control) were included in the pre-existing renal dysfunction group. Pooled analysis suggested a significant reduction in CIN among this group (OR, 0.76; 95% CI, 0.61–0.93; p?=?0.008). However, the nine trials comparing NAC versus control among patients with diabetes (NAC, 367 subjects; control, 358 subjects) showed no benefit of NAC for prevention of CIN (OR?=?0.87; 95% CI, 0.58–1.30; p?=?0.50). No significant heterogeneity was detected (p?=?0.07; I²?=?34% for the group of pre-existing renal dysfunction; p?=?0.40; I²?=?5% for the group of diabetes). Conclusion: Our results suggest that NAC decreases the incidence of contrast-induced nephropathy among patients with pre-existing renal insufficiency. The benefit was not existed in patients with diabetes.     

昂丹司琼预防妇科腹腔镜手术恶心呕吐的Meta分析

目的 系统评价昂丹司琼预防妇科腹腔镜全麻术后恶心呕吐(postoperative nausea and vomiting,PONV)的有效性和安全性. 方法 电子检索中国学术期刊全文数据库(CNKI)、中国生物医学文献数据库(CBM)、重庆维普中文科技期刊全文数据库、万方数据库、Pubmed、Springer、Embase、Web of knowledge数据库,并查阅所获文献的参考文献,收集1995～2012年发表的有关昂丹斯琼预防妇科腹腔镜全麻PONV的随机对照试验(randomized controlled trials,RCTs).按Cochrane Handbook5.0.1对纳入文献进行质量评价和资料提取,统计学分析采用Stata11.0软件. 结果共纳入18个RCT,包括1 597例患者.Meta分析结果显示:①有效性:昂丹司琼单次静脉注射能降低妇科腹腔镜全麻PONV的发生率[(RR=0.210,95％CI=0.164～0.268)];昂丹司琼4 mg与8 mg单次静脉注射对预防妇科腹腔镜全麻术后患者24 h PONV效果相当[(RR=0.948,95％CI=0.433～2.075)];手术前期应用昂丹司琼较术毕应用患者PONV发生率更低[(RR=0.450,95％CI=0.290～0.698)];昂丹斯琼4 mg或氟哌利多1.25 mg～2 mg静脉注射患者术后24 h PONV发生率相同[(RR=1.36,95％CI=0.74～2.51)];昂丹司琼联合氟哌利多静脉注射预防术后PONV发生较单独使用昂丹司琼效果更好[(RR=3.56,95％CI=1.74～7.29)].②安全性:昂丹司琼静脉注射不增加头痛、低热的发生率. 结论 昂丹司琼4 mg术前静脉注射能明显降低妇科腹腔镜全麻PONV的发生率,但并不能降低头痛、低热等副作用的发生率.昂丹司琼联合小剂量氟哌利多静脉注射较单独使用昂丹司琼对预防妇科腹腔镜全麻PONV的发生效果更好.     

Renin-angiotensin system blockades and contrast-induced nephropathy: a meta-analysis

Objective To evaluate the effects of renin-angiotensin system (RAS) blockades [angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II type 1 receptor blockers (ARB)]on contrast-induced nephropathy (CIN) in patients undergoing angiography. Methods Pubmed, Embase, Cochrane library, Wanfang database and CNKI were searched. The literature limited range was from their start year to July 2015. Randomized controlled trials (RCTs) and non-randomized controlled trials of renin-angiotensin system blockades in influencing CIN were assessed. Two investigators extracted data and performed quality analysis independently from all trials included. Rev man 5.3 software was used. Results 16 trials with a total of 15 897 patients were identified. There were 7490 patients who received renin-angiotensin system blockades and 8407 patients in control group. The meta analysis revealed a higher CIN incidence in ACEI/ARB group than that in control group (14.35% vs 12.13%, P=0.04, OR=1.44, 95%CI 1.01-2.04). For patients with renal insufficiency, ACEI/ARB group had a higher CIN incidence than control group (12.23% vs 7.32%, P= 0.02, OR=1.80, 95%CI 1.10-2.94), and the serum creatinine changes in ACEI/ARB group were higher than those in control group. There was statistical difference in serum creatinine changes between groups (P=0.02, MD=0.08, 95%CI 0.02-0.15). Conclusions Renin-angiotensin system blockades can increase the incidence of CIN in patients undergoing angiography. Renin-angiotensin system blockades can contribute to CIN for patients with renal insufficiency.     

Neutrophil gelatinase-associated lipocalin (NGAL): a promising biomarker of contrast-induced nephropathy after computed tomography

Contrast-induced nephropathy (CIN) is a common cause of hospital-acquired acute kidney injury (AKI) and a source of significantly increased short- and long-term mortality. Studies of large cohorts have revealed that more than half of these cases are in subjects undergoing cardiac catheterization and intra-arterial coronary angiography, and nearly a third follow computed tomography (CT) scans. Neutrophil gelatinase-associated lipocalin (NGAL) represents an early predictive troponin-like biomarker for AKI. Its role in the timely diagnosis of CIN has already been examined in adults and children undergoing coronary angiography and a meta-analysis revealed a very good performance of plasma or urine NGAL in the prediction of CIN. Much of these data have been extrapolated to patients receiving intravenous (IV) contrast agent for CT scans, although major differences in patient populations, contrast volume administered and intra-procedural complications between the two settings exist. In this context, a recent prospective study by our group evaluated plasma NGAL, measured using standardized Τriage® NGAL test (Biosite Incorporated, San Diego, CA) at baseline and 6-h post-procedure, for early detection of CIN among hospitalized patients undergoing elective contrast-enhanced CT. CIN, defined as an increase in serum creatinine (SCr) of >25% or >0.5?mg/dL from baseline within 48-h post-procedure, was found in 8.51% of subjects. In contrast, significant elevation of plasma NGAL was found at 6-h post-procedure with excellent performance characteristics. This review presents the current status of NGAL in the prediction of CIN after IV contrast administration among hospitalized patients undergoing elective contrast-enhanced CT.     

Periprocedural effects of statins on the incidence of contrast-induced acute kidney injury: a systematic review and meta-analysis of randomized controlled trials

Abstract

Background: The reports on the efficacy of statins for the prevention of contrast-induced acute kidney injury (CIAKI) remain controversial. The objective of this meta-analysis was to assess the effect of statins for the prevention of CIAKI. Methods: Comprehensive literature searches for randomized controlled trials (RCTs) of periprocedural statin treatment for prevention of CIAKI were performed using MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials Systematic Reviews and clinicaltrials.gov from inception until May 2014. The primary outcome was the incidence of CIAKI. Results: Thirteen prospective RCTs were included in our analysis. Of 5803 patients with contrast exposures, 304 patients (5.2%) had CIAKI. Patients in the statin group had an overall lower incidence of CIAKI (3.6%) compared to the control group (6.9%). Intravenous (IV) fluid hydration was used in both groups of all included studies for prevention of CIAKI. There was a significant protective effect of periprocedural statins on the incidence of CIAKI when compared to the control group [risk ratios (RRs): 0.49; 95% CI: 0.37–0.66, I² of 25%]. Conclusions: Our study demonstrates a statistically significant protective effect of statin treatment during procedures with contrast exposures. This finding suggests the use of statins in addition to standard IV crystalloid hydration may be beneficial in the prevention of CIAKI.     

Early predictive value of red cell distribution width for contrast-induced nephropathy in patients after enhanced computed tomography

Objective To explore the early predictive value of red cell distribution width (RDW) for contrast-induced nephropathy (CIN) in patients after enhanced computed tomography (CT). Methods A total of 218 patients who underwent enhanced CT between June 2015 and June 2017 at Huizhou Central Municipal Hospital were enrolled in this study. Patients were divided into CIN group and no-CIN group. The diagnostic criteria for CIN is an increase in serum creatinine (Scr) of more than 44.2 μmol/L or 25% of the baseline value within 3 days of contrast agent use. The general information and clinical characteristics in two groups were compared. The risk factors of CIN were analyzed by logistic regression analysis. The receiver operator characteristic curve (ROC) was used to assess the value of RDW for predicting the occurrence of CIN. Results Among 218 patients, 10(4.59%) patients had CIN. In the CIN group age, baseline Scr and baseline RDW were significantly higher, while hemoglobin, baseline estimated glomerular filtration rate (eGFR), red blood cell, white blood cell, albumin, and high-density lipoprotein cholesterol were significantly lower than those in the no-CIN group (all P＜0.05). Binary logistic regression analysis revealed that baseline RDW (OR=2.250, 95% CI 1.031-4.911, P=0.042) and eGFR (OR=0.963, 95% CI 0.928-0.999, P=0.044) were correlated with the occurrence of CIN. ROC analysis confirmed the area under the curve of RDW as a predictor of CIN was 0.798 (P＜0.001). The cut-off value of RDW was 14.5%, and the diagnostic sensitivity and specificity in CIN were 70.00% and 85.58%, respectively. Conclusions Increased baseline RDW and decreased eGFR are the risk factors of the occurrence of CIN after enhanced CT. RDW has a good predictive value, and it may be a good biomarker for the early diagnosis of CIN.     

Safety and efficacy of hemodialysis and peritoneal dialysis in treating end-stage diabetic nephropathy: a meta-analysis of randomized controlled trials

International Urology and Nephrology - Present investigation aims to elucidate safety and efficacy of hemodialysis as well as peritoneal dialysis in treating end-stage diabetic nephropathy. We...