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.     

Prevention of contrast-induced nephropathy with volume supplementation

Volume supplementation remains the cornerstone for the prevention of contrast-induced nephropathy (CIN). Current evidence suggests that the combination of intravenous and oral volume supplementation effectively prevents CIN in low- and moderate-risk patients. Normal isotonic (0.9%) saline should be started 12 h before (or at least in the morning of) the contrast procedure with an infusion rate of 1 ml/kg of body weight per hour and be continued for 24 h. In addition, patients should be encouraged to drink plenty of fluids (tea, mineral water). The use of bicarbonate infusion may allow shorter volume supplementation periods. Combined intravenous and oral volume supplementation protocols feasible for outpatients who limit the intravenous infusion to the contrast procedure are under investigation. Future studies are necessary to define further details regarding the optimal use of volume supplementation.     

Prevention of contrast-induced nephropathy: a pharmacological overview

The use of contrast media in diagnostic procedures is a potential risk for the development of acute renal failure. To reduce the occurrence of contrast-induced nephropathy, assessment and subsequent minimization of risk factors is important. If risk factors are present, consider discontinuing concomitant nephrotoxic drugs, limiting exposure to contrast media or using an alternative imaging technique. Additionally, adequate intravenous hydration is universally recommended and should be employed in all patients.     

Prevention of contrast-induced nephropathy: a critical review

PURPOSE OF REVIEW: Although contrast-induced nephropathy (CIN) is common and portends a significant morbidity and mortality, only few large and well designed trials have assessed the available prophylactic measures and there are no clear evidence-based guidelines that can easily be adopted by the clinician. We critically discuss the evidence for periprocedural hydration, pharmacological agents, periprocedural withdrawal of medication, application of renal replacement therapy and the use of contrast media. RECENT FINDINGS: Pending confirmation of the superiority of sodium bicarbonate, NaCl 0.9% remains the fluid of choice for periprocedural hydration. A recent trial found a dose-dependent beneficial effect of acetylcysteine on CIN and mortality, adding to the controversy on the prophylactic use of this agent. Publication bias of acetylcysteine trials may have confounded the results of the meta-analyses, since negative results were more likely to be published as an abstract only. Periprocedural haemofiltration protected against CIN in a high-risk population, but the results require confirmation before the technique can be recommended. SUMMARY: Pending randomized controlled trials with rigorous scientific design, we propose practical mixed evidence-based and opinion-based guidelines for the prevention of CIN, using a stratification of patients into three risk groups, based on their renal function and a risk-prediction model.     

Follow-up of patients with contrast-induced nephropathy

In this chapter, we review the approach to following the patient after contrast is administered. We first discuss the clinical importance of renal injury for if there were no clinically significant consequences of this renal injury, we would have far less concern for the adequacy of follow-up. We next look at markers of renal injury and what tests are used in clinical practice to define contrast-induced nephropathy (CIN). Finally, we discuss the steps that should be taken in those who do develop CIN to limit the impact of the injury and protect them from future adverse events.     

Prevention of contrast-induced nephropathy with prostaglandin E1 in high-risk patients undergoing percutaneous coronary intervention

Purpose

Contrast-induced nephropathy (CIN) is an important complication in the use of iodinated contrast media. The present study aimed to assess the safety and efficacy of prostaglandin E₁ (PGE₁) in prevention of CIN in patients with high-risk factors undergoing percutaneous coronary intervention (PCI).

Methods

The study group consisted of 163 patients who had undergone a coronary intervention procedure between January 1, 2012 and October 31, 2012. Study participants were randomly assigned to either the PGE₁ group (82 patients) or the control group (81 patients). Patients in the PGE₁ group received PGE₁ intravenous infusion of 20 ng/kg/min for 6 h before and after the administration of contrast media. The control group received 0.9 % sodium chloride solution for routine hydration only. A nonionic, low-osmolality contrast agent was used in our laboratory at this time. Serum creatinine (Scr) values and estimated glomerular filtration rate were measured before and within 48 h of the administration of contrast agents. CIN was defined as an increase of ≥0.5 mg/dL or ≥ a 25 % increase in Scr concentrations over baseline within 48 h of angiography.

Results

The amount of contrast agent administered was similar for the PGE₁ and control groups (156 ± 63 vs. 161 ± 68 mL, P > 0.05). The incidence of CIN was lower in the PGE₁ group than in the control group (3.7 vs. 11.1 %, P < 0.05). No serious adverse effects were observed.

Conclusions

In patients with high-risk factors undergoing PCI, the use of PGE₁ for prevention of CIN is safe and efficacious.     

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.     

Efficacy of pentoxifylline in prevention of contrast-induced nephropathy in angioplasty patients

Background

Contrast-induced nephropathy (CIN) is an adverse consequence of contrast media use that results in significant morbidity and mortality and adds significant costs to diagnostic and interventional cardiology procedures. Various pathophysiological mechanisms have been proposed for CIN and various agents have been tested for its prevention. There is currently a general agreement that adequate pre-procedure hydration constitutes the cornerstone of prevention, yet there are reports of the use of some other agents with various efficacies. We prospectively tested pentoxifylline (PTX), an antioxidant, anti-inflammatory drug, for CIN prevention in patients undergoing coronary angioplasty.

Materials and methods

In this prospective, randomized, single-blind, single-center clinical trial, 286 consecutive patients were randomly assigned to the control group (n?=?146), with routine treatment and no PTX, or the study group (n?=?140), with routine treatment and PTX, 400?mg/tid from 24?h before to 24?h after coronary angioplasty. Serum creatinine was measured before and 2?days after the procedure. The primary end point was the occurrence of CIN within 48?h.

Results

The control and PTX groups were comparable in the overall predicted risk of CIN. Also, the type and volume of the contrast agent were not significantly different between the two groups. Following angioplasty, CIN occurred in 20 (13.69%) patients in the control group and in 12 (8.5%) patients in the study group; the difference was not statistically significant (P?=?0.17). Additionally, there was no mortality and need for hemodialysis in either group.

Conclusion

In angioplasty patients, the prophylactic oral use of PTX could be recommended for CIN prevention, although no statistically significant protective effect was documented.     

血红蛋白预测肝癌患者TACE术后对比剂肾病

目的评估血红蛋白(Hb)对肝细胞癌(HCC)患者TACE术后发生对比剂肾病(CIN)的预测价值。方法回顾性分析250例原发性HCC患者,共行417次TACE。采用倾向性匹配评分(PSM)法进行配对,以单因素及多因素Logistic回归分析评价CIN发病的危险因素,采用ROC曲线分析Hb水平对CIN的诊断效能。结果 PSM匹配前,417次TACE治疗前85次患者出现Hb降低、Hb正常332次;PSM匹配后,74对(即Hb降低、Hb正常分别74次)匹配成功。PSM匹配前,Hb降低时CIN发生率为10.59%(9/85),Hb正常时为4.52%(15/332),糖尿病、Hb、肌酐及胆红素为CIN发病的独立影响因素(P均0.05)。PSM匹配后,Hb降低时CIN发病率为10.81%(8/74),正常时为4.05%(3/74),Hb为CIN发病的独立影响因素(P0.05)。ROC曲线结果显示,女性:Hb预测肝癌患者TACE术后发生CIN的最佳截断值为93.5 g/L,诊断灵敏度为91.9%,特异度75.0%,AUC为0.83;男性:Hb预测肝癌患者TACE术后发生CIN的最佳截断值为104.0 g/L,诊断灵敏度为90.8%,特异度36.0%,AUC为0.65。结论 Hb是肝癌患者TACE术后发生CIN的独立影响因素。     

Risk factors for contrast-induced nephropathy

An increasing number of diagnostic imaging and interventional procedures require the use of radiographic contrast agents which has led to a parallel increase in the incidence of contrast-induced nephropathy (CIN). CIN is a serious clinical problem associated with increased morbidity and mortality, particularly in patients with chronic renal failure (see the Case Report). A key step to minimize CIN is to identify patients at risk of CIN. The aim of the present review was to summarize the knowledge about the risk factors of CIN, including the review of ultimate clinical research and developments.     

Prophylaxis of contrast-induced nephropathy with N-acetylcysteine

PURPOSE: Clinical trials evaluating N-acetylcysteine (NAC) for the prevention of radiocontrast-induced nephropathy (RCN) have reported mixed results. Despite formerly published meta-analyses and due to currently published RCTs, time has come to re-evaluate the current evidence of preventing RCN by administering NAC. METHODS: We performed a computerized search without restricted to a language to identify relevant published randomized clinical trials that evaluated N-acetylcysteine for the prevention of radiocontrast-induced nephropathy. Abstracted data from each trial included assessments of clinical outcomes, trial quality, and additional characteristics. The primary outcome of interest was the incidence of nephropathy after contrast administration. Data were combined using random effects models with the performance of standard tests to assess for heterogeneity and publication bias. Subgroup analyses were also performed. RESULTS: Twenty-eight trials involving 3 604 patients met our inclusion criteria. Trials varied in patient demographic characteristics, inclusion criteria, dosing regimens, and trial quality. The summary risk ratio for contrast-related nephropathy was 0.69 (95 % confidence interval: 0.57 to 0.82; P = 0.02), a statistically significant trend towards benefit in patients treated with N-acetylcysteine. This effect varied, however, across the 28 trials, and only eight of the 28 trials demonstrated significant results although higher-quality trials demonstrated a stronger benefit for N-acetylcysteine in general, few reported important elements of study design, such as concealment of allocation, placebo-controls, or double-blinding. Heterogenity was unexplained by subgroup analyses. SUMMARY AND CONCLUSIONS: N-acetylcysteine (NAC) may reduce the incidence of contrast-related nephropathy, but this finding is reported inconsistently across currently available trials. Large high-quality, clinical trials are needed before the application of N-acetylcysteine can be recommended in general for this indication.     

Bone morphogenic protein-7 serum level decreases significantly in patients with contrast-induced nephropathy

Background and Aim  

Previous studies have demonstrated that endogenous bone morphogenic protein-7 (BMP-7) level is reduced in acute kidney injury and administration of exogenous BMP-7 has a beneficial effect on kidney function. In spite of preventive management, contrast-induced nephropathy (CIN) is still the third cause of acute deterioration of kidney function in hospitalized patients. With this background in mind, we studied changes in serum BMP-7 in a group of patients with chronic kidney disease and contrast-induced nephropathy.     

不同剂量阿托伐他汀改善对比剂所致肾功能损害

目的探讨不同剂量阿托伐他汀对急性冠状动脉综合征(ACS)患者接受经皮冠状动脉介入术(PCI)因对比剂引起的肾功能损害的缓解作用及其可能机制。方法 80例接受PCI的ACS患者随机分为两组,术前2～3天每晚顿服阿托伐他汀40mg(40mg他汀组,n=40)或20mg(20mg他汀组,n=40)。分别于术前8h、术后第1天、第2天测定血超敏C反应蛋白(hsCRP)、胱抑素C(CysC)、血清肌酐(Scr)、血尿素氮(BUN),检测尿α1-微球蛋白(α1-MG)、转铁蛋白(TRF)、微量白蛋白(mALB),计算肌酐清除率(Ccr)和肾小球滤过率(GFR),并进行统计学分析。结果①PCI术后,40mg他汀组中未发现对比剂肾病(CIN)病例,20mg他汀组中1例患者发生CIN(2.50%)。②与术前相比,术后第1天两组患者的α1-MG、Scr及CysC均明显升高(P均0.05),Ccr及GFR明显降低(P均0.05);与术后第一天比,术后第二天两组患者的α1-MG、Scr及CysC均明显降低(P均0.05),而Ccr及GFR明显升高(P均0.05)。③与术前相比,两组患者术后第1天hsCRP均明显升高(P均0.05);与术前第1天相比,术后第2天hsCRP均无明显变化(P均0.05)。④组间相比,术前及术后两组患者BUN、TRF、mALB、Scr、Ccr、CysC、GFR及hsCRP的差异均无统计学意义(P均0.05)。结论 PCI术前2～3天服用阿托伐他汀可有效缓解对比剂所致肾功能损害,其作用机制可能与减轻炎症反应、改善血管内皮功能有关。     

Prevention of cardiac complications in peripheral vascular surgery

The prevalence of severe coronary artery disease in peripheral vascular patients exceeds 50 per cent. It is therefore not surprising that complications of coronary artery disease are the most common causes of mortality following peripheral vascular operations. If the incidence of cardiac complications is to be reduced, it is first necessary to identify patients at risk through screening tests that will reliably detect hemodynamically important coronary occlusive disease. The operative risk can then be reduced by modifying the magnitude of the procedure, taking measures that can enhance the tolerance for a specific operation, or employing a combination of both. Screening methods in current use include risk factor analysis, exercise testing, routine coronary angiography, and dipyridamole thallium-201 scintigraphy. The risk factor approach has the advantage of being widely applicable since it makes use of historical, physical, and electrocardiographic findings that are already familiar to surgeons and anesthesiologists. It is also inexpensive. However, it may overlook the patient who has no symptoms of coronary artery disease, possibly as a result of the sedentary lifestyle imposed by complications of peripheral vascular disease. The electrocardiographically monitored stress test will identify the asymptomatic patient with occult coronary disease and is helpful in predicting operative risk. However, a meaningful test is dependent on the patient's ability to exercise--an activity that is frequently limited by claudication, amputation, or arthritis. Exercise testing also suffers from a lack of sensitivity and specificity when compared with coronary arteriography. Routine preoperative coronary angiography overcomes the exercise limitation of treadmill testing but is not widely applicable as a screening test for reasons of cost and inherent risk. Dipyridamole thallium-201 scanning, on the other hand, is safe and of relatively low cost and does not require exercise. Further, it has a high degree of sensitivity and specificity when compared with coronary arteriography. It appears to be an accurate predictor of postoperative cardiac complications.     

Angiotensin converting enzyme inhibitors and contrast-induced nephropathy

The available data on the use of angiotensin-converting enzyme inhibitors, and the associated risks for contrast-induced nephropathy are sparse and conflicting. Nevertheless, it is a common practice to hold angiotensin-converting enzyme inhibitors before contrast media administration. The reduction of renal blood flow that occurs following the administration of contrast media may be due to the renin-angiotensin-aldosterone system causing constriction of the afferent arterioles. The influence of angiotensin-converting enzyme inhibitor administration on the development of contrast-induced nephropathy was discussed in this letter.