Prevention Of Contrast Medium-induced Nephropathy Research Articles

Atorvastatin alleviates iodinated contrast media-induced cytotoxicity in human proximal renal tubular epithelial cells.

Contrast media (CM)-induced nephropathy (CIN) is a serious complication of intravascularly applied radiocontrast media. At present, no drugs have been approved for the prevention of CIN. The present study aimed to explore the effects and potential mechanisms of atorvastatin on iodinated CM-induced cytotoxicity in the human proximal renal tubular epithelial cells. The cytotoxic effect of iohexol (50, 100 and 200 mg I/ml) and the protective effect of atorvastatin pretreatment (1, 20 and 40 µM) were assessed. The cytotoxicity of iohexol was evaluated via the MTT cell viability and lactate dehydrogenase assays. The amount of apoptotic cells was determined by flow cytometry. Morphological changes in HK-2 cells were observed via transmission electron microscopy. The mRNA expression of NOX4 and p22phox was measured through reverse transcription-quantitative polymerase chain reaction analysis. The cytotoxicity was induced by iohexol in HK-2 cells. Atorvastatin was identified to significantly alleviate the suppression of cell viability induced by iohexol. Notably, 40 µM atorvastatin also significantly reduced the mRNA expression of intracellular NOX4 and p22phox, and the percentage of apoptotic cells. Furthermore, morphological changes characteristic of injured cells were alleviated by atorvastatin pretreatment. These results suggest that atorvastatin exhibits a protective effect on HK-2 cells against iohexol-induced cytotoxicity through the downregulation of NOX4 and p22phox. Thus, atorvastatin is a potential therapeutic agent for the prevention of CIN and required further study.

Evaluation of different sodium bicarbonate regimens for the prevention of contrast medium-induced nephropathy.

IntroductionThe rapid decline in renal function caused by radiographic contrast agents usually is transient, but it can result in chronic kidney disease. The pathophysiology of contrast-induced nephropathy (CIN) is poorly understood, but it may include acute hypoxia-induced oxidative stress and free radicals generated within the acid environment of the renal medulla. Thus, the alkalization of urine by sodium bicarbonate has been regarded as resulting in the reduction of CIN. The aim of this study was to determine whether a long-duration sodium bicarbonate regimen is more effective than a short-duration regimen in reducing CIN.MethodsOne hundred patients were assigned randomly to treatment with sodium bicarbonate solution using either the short regimen (intravenous bolus 3 mL/kg/h of 166 mEq/L sodium bicarbonate for 1 hour immediately before radiocontrast) or the long regimen (initial intravenous bolus of 3 mL/kg/h of 166 mEq/L sodium bicarbonate for 6 hr). Patients with renal dysfunction (estimated glomerular filtration rate [eGFR], 60 mL/min/1.73 m2 or less) who underwent elective or emergent coronary angiography (CAG) with/without percutaneous coronary intervention (PCI) at Nephrology Department (Theodor Bilharz Research Institute) were enrolled in the study. Data were analyzed by SPSS version 12, using Kruskal Wallis, ANOVA, Chi square test and Spearman rank correlation coefficient.ResultsThere was a significant increase in serum creatinine and a decrease in eGFR 48 hr post-intervention in group 1 (short regimen) with no statically difference regarding those parameters group 2 (long regimen). Serum potassium clearly was decreased significantly post procedure in both groups.ConclusionsThe results of our study indicated that the long regimen of bicarbonate supplementation was a more effective strategy to prevent CIN than the short regimen.

Is hypoalbuminemia a prognostic risk factor for contrast-induced nephropathy in peritoneal dialysis patients?

ObjectiveResidual renal function (RRF) is an important predictor of outcome in peritoneal dialysis (PD) patients. Hypoalbuminemia was found to be an independent risk factor for the development of acute kidney injury. We investigated the possibility of an association between serum albumin levels and the development of iodine contrast media-induced nephropathy (CIN) in PD patients.MethodsA total of 103 PD patients who underwent invasive angiographies with exposure to iodine contrast media (ICM) were reviewed retrospectively. All patients received 0.9% saline intravenously at a rate of 75 mL per hour for 12 hours prior, during, and 12 hours after exposure to ICM. Acetylcysteine was given orally at a dose of 600 mg twice daily, on the day before and on the day of exposure to ICM. The nonionic, low-osmolar contrast agent iopromide was used at a mean dose of 75.0±15.2 mL. The changes in RRF from baseline to 1 week and 4 weeks after exposure to ICM were recorded. Outcomes of patients with serum albumin levels <3.8 g/dL and those with serum albumin levels ≥3.8 g/dL were compared. A reduction >30% in RRF at 7 days after exposure to ICM was considered CIN.ResultsCIN developed in 27.2% (28/103) of patients. Of the 103 patients, 59.2% (61) had serum albumin levels <3.8 g/dL. Of those, 37.7% (23/61) developed CIN, compared with 11.9% (5/42) of those with serum albumin levels ≥3.8 g/dL (P=0.004). After adjustment for all tested variables in a logistic regression with a stepwise selection model, serum albumin level at exposure to ICM was found to be the most powerful predictor of the development of CIN (odds ratio =4.5; confidence interval =1.5–13.0; P=0.006).ConclusionPD patients with serum albumin levels <3.8 g/dL should be monitored carefully when exposed to ICM. Serum albumin level may be considered a potential therapeutic target in the prevention of CIN and preservation of RRF in PD patients.

Ischemic Preconditioning for Prevention of Contrast Medium-Induced Nephropathy: Randomized Pilot RenPro Trial (Renal Protection Trial)

Background —Contrast-medium-induced acute kidney injury is associated with substantial morbidity and mortality. The underlying mechanism has been partially attributed to ischemic kidney injury. The aim of this randomized, double-blind, sham-controlled trial was to assess the impact of remote ischemic preconditioning on contrast-medium-induced acute kidney injury. Methods and Results —Patients with impaired renal function (serum creatinine >1.4 mg/dL and/or estimated glomerular filtration rate <60 mL/min/1.73 m2) undergoing elective coronary angiography were randomized in a 1:1 ratio to standard care with (n=50) or without ischemic preconditioning (n=50; intermittent arm ischemia through four cycles of 5-min inflation and 5-min deflation of a blood-pressure cuff). Overall, both study groups were at high risk to develop contrast-medium-induced acute kidney injury using Mehran risk score. The primary endpoint was the incidence of contrast-medium-induced kidney injury, defined as an increase of serum creatinine ≥ 25 % and/or ≥ 0.5 mg/dL above baseline at 48 hours after contrast-medium exposure. Contrast-medium-induced acute kidney injury occurred in 26 patients (26%), 20 (40%) in the control group and 6 (12%) in the remote ischemic preconditioning group (OR 0.21; 95% CI 0.07-0.57; P=0.002). No major adverse events were related to remote ischemic preconditioning. Conclusions —Remote ischemic preconditioning before contrast-medium use prevents contrast-medium-induced acute kidney injury in high risk patients. Our findings merit a larger trial to establish remote ischemic preconditioning on clinical outcomes. Clinical Trial Registration Information —www.germanctr.de; Identifier: U1111-1118-8098.

Intrarenal application of N-acetylcysteine for the prevention of contrast medium-induced nephropathy in primary angioplasty

Contrast medium-induced nephropathy (CIN) is a well-known complication of coronary angiographic procedures, especially in patients treated with primary angioplasty. To prevent CIN, we examined using a local application of N-acetylcysteine (NAC) for the prevention of CIN during primary angioplasty. We hypothesized that a local application of NAC into the renal arteries would provide the benefit of a higher local concentration, lower first-pass metabolism, and faster efficacy. To evaluate the effects of NAC by the intrarenal route, we performed a prospective, randomized clinical study in patients with acute myocardial infarction treated with primary angioplasty. Participants were 312 patients with ST-segment elevation myocardial infarction undergoing primary angiography. Eligible patients were randomly assigned to receive intravenous NAC, intrarenal NAC, or placebo. Overall, CIN occurred in 74 (23.7%) of the 312 patients. The rate of CIN was 25% in the intravenous NAC group, 22.9% in the intrarenal NAC group, and 23.2% in the placebo group, with no significant effect seen for either treatment (P=0.64). We did find a significant correlation between CIN and ejection fraction (P=0.05) and baseline renal function (P=0.01). Both intrarenal and intravenous applications of NAC failed to show any benefit over placebo in the prevention of CIN. This result shows that NAC application does not have any prophylactic effect, dose dependent or otherwise, on CIN, as previously reported. Our results suggest that more attention should be paid to optimize hemodynamic variables for the prevention of CIN.

Impact of sodium bicarbonate administration and N-acetylcysteine on the prevention of contrast media-induced nephropathy in endovascular aortic aneurysm repair

Impact of sodium bicarbonate administration and N-acetylcysteine on the prevention of contrast media-induced nephropathy in endovascular aortic aneurysm repair

Sodium chloride vs. sodium bicarbonate for the prevention of contrast medium-induced nephropathy: a randomized controlled trial

The most effective regimen for the prevention of contrast-induced nephropathy (CIN) remains uncertain. Our purpose was to compare two regimens of sodium bicarbonate with 24 h sodium chloride 0.9% infusion in the prevention of CIN. We performed a prospective, randomized trial between March 2005 and December 2009, including 258 consecutive patients with renal insufficiency undergoing intravascular contrast procedures. Patients were randomized to receive intravenous volume supplementation with either (A) sodium chloride 0.9% 1 mL/kg/h for at least 12h prior and after the procedure or (B) sodium bicarbonate (166 mEq/L) 3 mL/kg for 1 h before and 1 mL/kg/h for 6 h after the procedure or (C) sodium bicarbonate (166 mEq/L) 3 mL/kg over 20 min before the procedure plus sodium bicarbonate orally (500 mg per 10 kg). The primary endpoint was the change in estimated glomerular filtration rate (eGFR) within 48 h after contrast. Secondary endpoints included the development of CIN. The maximum change in eGFR was significantly greater in Group B compared with Group A {mean difference -3.9 [95% confidence interval (CI), -6.8 to -1] mL/min/1.73 m2, P = 0.009} and similar between groups C and B [mean difference 1.3 (95% CI, -1.7-4.3) mL/min/1.73 m(2), P = 0.39]. The incidence of CIN was significantly lower in Group A (1%) vs. Group B (9%, P = 0.02) and similar between Groups B and C (10%, P = 0.9). Volume supplementation with 24 h sodium chloride 0.9% is superior to sodium bicarbonate for the prevention of CIN. A short-term regimen with sodium bicarbonate is non-inferior to a 7 h regimen. ClinicalTrials.gov Identifier: NCT00130598.

Intravenous N-Acetylcysteine in the Prevention of Contrast Media-Induced Nephropathy

To define the clinical role of intravenous N-acetylcysteine for prophylaxis of contrast-induced nephropathy (CIN). Randomized controlled clinical trials were identified using a search of MEDLINE (1990-September 2010) with the search terms acetylcysteine, N-acetylcysteine, NAC, intravenous, IV, nephropathy, nephrotoxic, radiocontrast, contrast, and media. The search was limited to studies published in English. Additional pertinent literature was retrieved by reviewing references of the articles obtained in the initial search. N-Acetylcysteine is a vasodilator and antioxidant that has been investigated for the prevention of CIN. In the majority of clinical trials, neither oral nor intravenous N-acetylcysteine has demonstrated clinical benefits at preventing CIN. The pharmacodynamic and pharmacokinetic profiles of intravenous N-acetylcysteine are significantly different from those of the oral product in that intravenous administration bypasses extensive first-pass metabolism. Studies have suggested that N-acetylcysteine directly affects serum creatinine levels in a way that is not associated with improvement of kidney function. Only intravenous N-acetylcysteine doses that were higher than the oral doses showed potential benefits, but they were associated with significant adverse events. Furthermore, the study populations were heterogeneous, including patients with various levels of kidney function and other risk factors, and the clinical definition of CIN was not well established. No conclusive evidence has shown that intravenous N-acetylcysteine is safe and effective in preventing CIN. Further clinical trials to define its role are warranted.

Prevention of contrast media-induced nephropathy by isotonic sodium bicarbonate: a meta-analysis

The clinical value of hydration therapy using sodium bicarbonate in the prevention of contrast media-induced nephropathy is subject of controversy. This meta-analysis of randomized clinical trials was performed to determine whether hydration therapy using sodium bicarbonate consistently differs from control hydration regimens with normal saline in its preventive effects upon radiocontrast media-induced renal dysfunction. Randomized clinical trials comparing sodium bicarbonate with a control regimen for prevention of contrast media-induced nephropathy were selected by multiple methods, including computer searches of bibliographic databases, perusal of reference lists, and manual searching. Major findings were qualitatively summarized. In addition, a quantitative meta-analysis was performed on renal dysfunction data. Altogether, 9 randomized clinical trials with a total of 2,043 patients were included. The pooled odds ratio was 0.45 (confidence interval, 0.26-0.79), indicating a significant treatment benefit of sodium bicarbonate compared to normal saline. Heterogeneity was detectable (p=0.016) and evidence of publication bias was present (p=0.012). After adjustment for presumed unpublished trials after trim-and-fill analysis, the estimated pooled odds ratio was 0.65 (confidence interval, 0.36-1.20). This meta-analysis confirms that, based on currently available randomized trials, bicarbonate therapy is effective in preventing contrast media-induced nephropathy. However, study heterogeneity and publication bias are substantial, and therefore further controlled clinical trials are needed.

Sodium Bicarbonate vs Sodium Chloride for the Prevention of Contrast Medium–Induced Nephropathy in Patients Undergoing Coronary Angiography

Sodium bicarbonate has been suggested as a possible strategy for prevention of contrast medium-induced nephropathy, a common cause of renal failure associated with prolonged hospitalization, increased health care costs, and substantial morbidity and mortality. To determine if sodium bicarbonate is superior to sodium chloride for preventing contrast medium-induced nephropathy in patients with moderate to severe chronic kidney dysfunction who are undergoing coronary angiography. Randomized, controlled, single-blind study conducted between January 2, 2006, and January 31, 2007, and enrolling 353 patients with stable renal disease who were undergoing coronary angiography at a single US center. Included patients were 18 years or older and had an estimated glomerular filtration rate of 60 mL/min per 1.73 m(2) or less and 1 or more of diabetes mellitus, history of congestive heart failure, hypertension, or age older than 75 years. Patients were randomized to receive either sodium chloride (n = 178) or sodium bicarbonate (n = 175) administered at the same rate (3 mL/kg for 1 hour before coronary angiography, decreased to 1.5 mL/kg per hour during the procedure and for 4 hours after the completion of the procedure). The primary end point was a 25% or greater decrease in the estimated glomerular filtration rate on days 1 through 4 after contrast exposure. Median patient age was 71 (interquartile range, 65-76) years, and 45% had diabetes mellitus. The groups were well matched for baseline characteristics. The primary end point was met in 13.3% of the sodium bicarbonate group and 14.6% of the sodium chloride group (relative risk, 0.94; 95% confidence interval, 0.55-1.60; P = .82). In patients randomized to receive sodium bicarbonate vs sodium chloride, the rates of death, dialysis, myocardial infarction, and cerebrovascular events did not differ significantly at 30 days (1.7% vs 1.7%, 0.6% vs 1.1%, 0.6% vs 0%, and 0% vs 2.2%, respectively) or at 30 days to 6 months (0.6% vs 2.3%, 0.6% vs 1.1%, 0.6% vs 2.3%, and 0.6% vs 1.7%, respectively) (P > .10 for all). The results of this study do not suggest that hydration with sodium bicarbonate is superior to hydration with sodium chloride for the prevention of contrast medium-induced nephropathy in patients with moderate to severe chronic kidney disease who are undergoing coronary angiography. clinicaltrials.gov Identifier: NCT00312117.

Contrast Medium‐Induced Nephropathy: Strategies for Prevention

Contrast medium-induced nephropathy (CIN) is the third leading cause of acute renal failure in hospitalized patients. The exact mechanism by which contrast media induce renal failure is complex and not completely understood. Alteration in renal hemodynamics and direct toxicity to tubular cells have been proposed. The most important risk factor for development of CIN is preexisting renal insufficiency. Identification of patients with risk factors for development of CIN is essential, as measures for prevention of CIN can be instituted. Administration of fluids such as sodium chloride has been the traditional cornerstone of preventive therapy. Alkalization of tubular fluid with intravenous sodium bicarbonate has dramatically reduced the frequency of CIN in patients with baseline impaired renal function. Based on available evidence, use of sodium bicarbonate constitutes the most reliable and effective option. Prevention of CIN has also been achieved with periprocedural use of N-acetylcysteine, but not as consistently as with sodium bicarbonate. Although many studies evaluated different N-acetylcysteine dosages and routes of administration, the optimal regimen has yet to be determined. Combinations of these preventive therapies are just emerging and require further research.

Empfehlungen zur Prophylaxe der Nebenwirkungen bei intravasaler Applikation jodhaltiger Kontrastmittel

Iodinated contrast media are widely used in computed tomography and angiography. Adverse reactions such as contrast-medium induced nephropathy (CIN), anaphylactoid reactions and iodine-induced thyrotoxicosis are associated with intravasal administration of contrast agents. Iodinated contrast agents are generately considered to be safe, but in rare cases they can cause severe life threatening situations. In this review we present an overview about the incidence, pathways, and risk factors of adverse reactions. Simple schemes including hydration protocols for prevention of CIN, medication for prophylaxis of iodine-induced thyrotoxicosis with thyreostatics and anaphylactoid reactions with histamine antagonists and corticosteroids are suggested.

Improved estimation of glomerular filtration rate by serum cystatin C in preventing contrast induced nephropathy by N-acetylcysteine or zinc--preliminary results

Prevention of contrast media (CM) induced nephropathy (CIN) by prophylaxis (e.g. N-acetylcysteine; NAC) is controversially discussed. Up to now, assessment of kidney function has been based on measurements of serum creatinine, although this biomarker has several limitations. We investigated NAC and zinc (Zn) for the prevention of CIN by monitoring creatinine and cystatin C. In a prospective, placebo-controlled, double blind trial, patients with moderately impaired kidney function receiving low-osmolar, non-ionic CM were randomly assigned to an oral treatment for 2 days with 1.2 g/day of NAC (n = 19), for 1 day with 60 mg/day of Zn (n = 18) or placebo (n = 17). All patients received peri-procedurally 1 ml/kg/h of 0.45% saline for 24 h. At baseline, prior to exposure of CM, 2 and 6 days after CM, creatinine and cystatin C were measured. There was no difference in the incidence of CIN, but a significant drop in creatinine (P < 0.05) was observed in all patients during volume expansion. Creatinine showed no increase after CM and it was normalized to the baseline values in all groups at the study end. In contrast, 2 days after CM there was a significant rise in cystatin C in the Zn (P = 0.012) and the placebo (P = 0.041) group, whereas NAC prevented this deterioration of kidney function. Cystatin C seems to reflect CM-induced changes in kidney function better than creatinine. NAC and Zn have no effect in preventing CIN by the standard definition, but based on cystatin C we can confirm a preventive effect of NAC. It appears mandatory to assess kidney function by cystatin C in CIN intervention trials, because relying on creatinine can be misleading.

A randomized controlled trial comparing hydration therapy to additional hemodialysis or N-acetylcysteine for the prevention of contrast medium-induced nephropathy

Contrast medium-induced nephropathy (CIN) is a serious complication with increasing frequency and an unfavorable prognosis. Previous analyses of surrogate parameters have suggested beneficial effects of hemodialysis that are assessed in this randomized clinical trial. We performed a prospective single-center trial in 424 consecutive patients with serum creatinine concentrations between 1.3- 3.5 mg/dl who underwent elective coronary angiography. Patients were randomized to one of three treatment strategies with all patients receiving pre- and postprocedural hydration: One group received no additional therapy, patients in the second group were hemodialyzed once, and the third group received oral N-acetylcysteine. The frequency of CIN (defined as an increase in serum creatinine>or=0.5 mg/dl) from 48 to 72 h after catheterization was 6.1% in the hydration-only group, 15.9% with hemodialysis treatment, and 5.3% in the N-ACC group (intention-to-treat analysis; P=0.008). There were no differences between the treatment groups with regard to increased (>or=0.5 mg/dl) serum creatinine concentrations after 30-60 days (4.8%, 5.1%, and 3.1%, respectively; P=0.700). Analyses of long-term follow-up (range 63 to 1316 days) by Cox regressions models of the study groups found quite similar survival rates (P=0.500). In contrast to other (retrospective) studies, long-term survival of patients with vs those without CIN within 72 h was not different, but patients who still had elevated creatinine concentrations at 30-60 days suffered from a markedly higher 2-year mortality (46% vs 17%, P=0.002). In conclusion, hemodialysis in addition to hydration therapy for the prevention of CIN provided no evidence for any outcome benefit but evidence for probable harm. Increased creatinine concentrations at 30-60 days, but not within 72 h, were associated with markedly reduced long-term survival.

Facts and fallacies concerning the prevention of contrast medium–induced nephropathy

The aim of this article is to extract from recent medical literature and nephrologic practice the facts and fallacies concerning the possible prophylaxis of contrast medium-induced nephropathy. A MEDLINE/PubMed search (1985 to January 2006) was conducted, including all relevant articles investigating the pathogenesis and prevention of contrast medium-induced nephropathy from a nephrologic critical point of view. Considerable efforts have been made to develop pharmacologic therapy for the prevention of contrast medium-induced nephropathy, especially in patients at risk, such as elderly subjects and those with preexisting renal impairment, hypovolemia, or dehydration. There is general consensus that hydration protocols implemented before and after imaging with contrast medium may be effective in preventing contrast medium-induced nephropathy. However, definitive and convincing data related to amounts to be infused, infusion timing, and type of solutions (half-isotonic, isotonic saline solution, or bicarbonate) are lacking. Forced diuresis with furosemide or mannitol and use of dopamine, together with concomitant hydration, have been proved to be ineffective or even more risky in the event of inadequate maintenance of euvolemia. Various direct or indirect vasodilators have been investigated (atrial natriuretic peptide, calcium channel blockers, angiotensin-converting enzyme inhibitors, and endothelin receptor antagonists), yet results have been inconsistent and inconclusive. Recent large meta-analyses concerning the protective role of antioxidant action of N-acetylcysteine have led to the conclusion that the statistical significance of the results is borderline. Preventive hemodialysis has not proved to be useful; on the contrary, it might worsen the clinical conditions by inducing hypotension. Hemofiltration, despite some positive studies, is too complex and cannot be used extensively. : It is believed that prevention is actually achieved by correcting hypovolemia, dehydration, or both. Normalization of body fluids is probably the true objective to be achieved by preventive measures in all patients, not only in those at risk. Because limited data have been collected in intensive care units, at present, no firm or specific recommendations can yet be provided for the critically ill.

How to avoid CIN: guidelines from the European Society of Urogenital Radiology

The Contrast Media Safety Committee of the European Society of Urogenital Radiology (ESUR) has looked at the effects of contrast media (CM) on the kidney including prevention of contrast medium-induced nephropathy (CIN) as well as at the possibility of identifying patients with increased risk of CIN nephropathy. This has resulted in five reports dealing with (i) serum creatinine; (ii) contrast medium-induced nephrotoxicity; (iii) haemodialysis and contrast media; (iv) use of gadolinium CM instead of iodinated CM; and (v) CM injection in diabetic patients receiving metformin. The review presents an overview of four of these five reports.