Radiocontrast Media Research Articles

Theophylline for Prevention of Contrast-Induced Nephropathy

Contrast-induced nephropathy (CIN) is an important cause of declines in kidney function and is related to greater morbidity, health care costs, and mortality. Adenosine has been proposed to contribute to the pathophysiological process of CIN. We performed a systematic review and meta-analysis of theophylline, an adenosine antagonist, for the prevention of CIN. Studies were identified in all languages by search of MEDLINE (1966 through November 2003), EMBASE (1980 through week 44 [November] of 2003), and the Cochrane Controlled Clinical Trials Register (1996 through November 2003) databases and selected conference proceedings. We searched for randomized controlled trials comparing theophylline vs control in patients receiving radiocontrast media for angiography or computed tomography. Our primary outcome measures were the risk of CIN, the difference in serum creatinine levels between theophylline and control groups at 48 hours and need for dialysis. Nine randomized controlled trials involving 585 patients were identified and included for analysis. Theophylline protocols and definitions of CIN varied across studies. There was evidence of heterogeneity of results across trials (Q = 9.77; P = .08); therefore, pooled values require cautious interpretation. The overall pooled odds ratio (OR) using a conservative random-effects model was 0.40 (95% confidence interval [CI], 0.14 to 1.16; P = .09) indicating a trend toward reduction in the incidence of CIN with theophylline use. The pooled estimate for the difference in 48-hour serum creatinine levels between the theophylline and control groups was -0.17 mg/dL (95% CI, -0.28 to -0.06 mg/dL) (-15.2 micromol/L [95% CI, -24.6 to -5.7 micromol/L]) (P = .002), indicating that theophylline may be protective in CIN. The incidence of CIN requiring dialysis was uncommon and reported in only 1 case. Theophylline may reduce the incidence of CIN with an efficacy that is perhaps comparable to that reported in studies of N-acetylcysteine. However, findings are inconsistent across studies. A large, well-designed trial that incorporates the evaluation of clinically relevant outcomes is required to more adequately assess the role for theophylline in CIN prevention.

Radiocontrast-Induced Acute Renal Failure

The intravascular administration of iodinated radiocontrast media can lead to acute renal dysfunction. Even small changes in renal function have been associated with increased morbidity and mortality, making the prevention of radiocontrast nephropathy of paramount importance. This review summarizes the principal risk factors for radiocontrast nephropathy and evidence-based preventive strategies that should be used to limit its occurrence. Risk factors for radiocontrast nephropathy include preexistent kidney disease, diabetes mellitus, dose of radiocontrast used, advanced congestive heart failure, and intravascular volume depletion. Proven preventive measures include volume expansion with intravenous saline or sodium bicarbonate and the use of low-osmolar or iso-osmolar radiocontrast media. Studies evaluating N-acetylcysteine have been conflicting, with meta-analyses suggesting a small beneficial effect. Studies of other pharmacologic agents have not demonstrated clinical benefit.

Delayed type hypersensitivity reaction caused by non-ionic Radiocontrast media

Delayed type hypersensitivity reaction caused by non-ionic Radiocontrast media

Radiocontrast anaphylaxis with failure of premedication

Radiocontrast media (RCM) is used commonly in clinical practice, and can be associated with significant adverse effects. We report a patient who experienced severe anaphylaxis after being given multiple drugs. Challenge testing established allergy to both RCM and ceftriaxone. Premedication did not prevent recurrence of anaphylaxis on repeat challenge with RCM. The haemodynamic and serum tryptase consequences of the challenges are discussed, and a summary of RCM allergy is provided.

Anaphylactoid reactions to radiocontrast media

Adverse reactions to contrast material are a concern because iodinated contrast materials are commonly used drugs. The risk for adverse reaction is 4% to 12% with ionic contrast materials and 1% to 3% with nonionic contrast materials. The risk for severe adverse reaction is 0.16% with ionic contrast materials and 0.03% with nonionic contrast materials. The death rate, one to three per 100,000 contrast administrations, is similar for both ionic and nonionic agents. More than 90% of adverse reactions with nonionic contrast materials are anaphylactoid. The types of severe reactions seen with nonionic contrast administration were initially predominantly anaphylactoid. With the advent of helical CT angiography, the reactions are now predominantly attributable to cardiopulmonary decompensation. With the widespread use of nonionic contrast materials, adverse reactions are now seen less frequently. Skills involved in evaluating and treating adverse reactions are not as frequently used. Periodic reviews and updates of specific treatment plans for various reactions with the physicians and staff who use contrast material are very important to ensure optimal preparedness. The key to successful treatment is preparation and early intervention.

Effect of N-Acetylcysteine in Prevention of Contrast-Induced Nephropathy after Coronary Angiography

Background and Objectives:Contrast-induced nephropathy (CIN) is associated with increased morbidity and mortality in coronary angiography. Although the mechanism is unclear, N-acetylcysteine (NAC) is known to protect against CIN. Preliminary studies with NAC have found conflicting results for the prevention of CIN in patients undergoing coronary angiography. This study was designed to evaluate the efficacy and safety of NAC for the prevention of CIN in patients undergoing coronary angiography. Subjects and Methods:48 patients with chronic renal insufficiency (mean (±SD) serum creatinine concentration, 2.06±0.56 mg/dL), who were undergoing coronary angiography with a nonionic, low-osmolar contrast agent, were prospectively studied. Pa- tients were randomly assigned to receive either the antioxidant, NAC (600 mg orally twice daily), and 0.45% saline intravenously (n=25), before and after administration of contrast agents, or saline only (n=23). The renal function parameters were assessed 48 hour before and after radiocontrast media administration. Results:14 of the 48 patients (29%) showed an increase in the 0.5 mg/dL serum creatinine concentration after 48 hours of contrast media administration: 4 of the 25 patients in the NAC group (16%) and 10 of the 23 in the control group (43%; p=0.036; relative risk, 0.37; 95% confidence interval, 1.04 to 7.79). In the NAC group, the mean serum creatinine concentration insignificantly increased (p=0.54), from 2.2±0.8 to 2.3±0.9 mg/dL, after 48 hours of contrast media administration; whereas, in the control group, the mean serum creatinine concentration significantly increased (p=0.011), from 1.9±0.4 to 2.2±0.8 mg/dL. The absolute change in serum creatinine concentration was significantly greater in the control than the NAC group (p=0.044). Conclusion:Prophylac- tic oral administration of the antioxidant NAC, along with hydration, prevents the decrease in the renal func- tion induced by a nonionic, low-osmolality contrast agent in patients with chronic renal insufficiency. (Korean Circulation J 2005;35:696-701)

Análisis crítico de un artículo: Acetilcisteína para prevenir falla renal por medio de contraste Birck R, Krzossok S, Markowetz F, Schnulle P, van der Woude FJ, Braun C. Acetylcysteine for prevention of contrast nephropathy: meta-analysis. Lancet 2003; 362 (9384): 598-603

Background: Contrast nephropathy is associated with increased in hospital morbidity and mortality and leads to extension of hospital stay in patients with chronic renal insufficiency. Acetylcysteine seems to be a safe and inexpensive way to reduce contrast nephropathy. We aimed to assess the efficacy of acetylcysteine to prevent contrast nephropathy after administration of radiocontrast media in patients with chronic renal insufficiency. Methods: We did a meta-analysis of randomized controlled trials comparing acetylcysteine and hydration with hydration alone for preventing contrast nephropathy in patients with chronic renal insufficiency. The trials were identified through a combined search of the BIOSIS+/RRM, MEDLINE, Web of Science, Current Contents Medizin, and The Cochrane Library Databases. We used incidence of contrast nephropathy 48 h after administration of radiocontrast media as an outcome measure. Findings: Seven trials including 805 patients were eligible according to our inclusion criteria and were analyzed. Overall incidence of contrast nephropathy varied between 8% and 28%. Since significant heterogeneity was indicated by the Q statistics (p=0.016) we used a random effects model to combine the data. Compared with periprocedural hydration alone, administration of acetylcysteine and hydration significantly reduced the relative risk of contrast nephropathy by 56% (0.435 [95% CI 0.215-0.879], p=0.02) in patients with chronic renal insufficiency. Meta-regression revealed no significant relation between the relative risk of contrast nephropathy and the volume of radiocontrast media administered or the degree of chronic renal insufficiency before the procedure. Interpretation: Compared with periprocedural hydration alone, acetylcysteine with hydration significantly reduces the risk of contrast nephropathy in patients with chronic renal insufficiency. The relative risk of contrast nephropathy was not related to the amount of radiocontrast media given or to the degree of chronic renal insufficiency before the procedure

Plasma and urinary free 3-nitrotyrosine following cardiac angiography procedures with non-ionic radiocontrast media

Plasma and urinary free 3-nitrotyrosine following cardiac angiography procedures with non-ionic radiocontrast media

Low negative predictive value of skin tests in investigating delayed reactions to radio-contrast media.

Delayed reactions to radio-contrast media (RCM) with positive skin tests are rare. We report the study of a series of 15 patients who presented delayed reactions to RCM, with an analysis of the clinical features and the results of standardized drug skin tests. Patch tests were performed with RCM and iodized antiseptics (IAs). If negative, prick tests were performed, followed by intradermal tests (IDTs), then intravenous administration under hospital surveillance. The main clinical features were maculopapular rashes or a macular rubella-like rashes. Patch tests were positive with RCM in 2 of 15 cases and with IAs in 4 of 15 cases. All the prick tests were negative. IDTs were positive at 24 h in 8 of 15 cases. 5 of 12 patients had a non-severe relapse of the rash upon receiving an RCM despite clearly negative skin tests with the readministered RCM. Visipaque cross-reacted with Iopamiron, Iomeron, Telebrix, Omnipaque, Xenetix and Hexabrix. Omnipaque cross-reacted with Hexabrix and Iopamiron. IDTs with delayed readings are of better value than patch tests in such patients. The readministration of RCM with negative IDTs must be performed with progressive amounts under hospital surveillance. Cross-reactions between various classes of RCM are frequent. The responsible epitopes are unknown. Iodine itself could be involved.

Anaphylaxis during surgical and interventional procedures

To describe the current evidence-based knowledge of the causes, diagnostic evaluation, and treatment of patients with anaphylaxis associated with surgical and interventional procedures. Articles published between 1966 and 2003 were identified in MEDLINE using the keywords anaphylactoid, anaphylaxis, anesthetics, antibiotics, cephalosporins, contrast media, colloids, flow cytometry, hypersensitivity, latex, neuromuscular depolarizing agents, neuromuscular nondepolarizing agents, penicillins, radioallergosorbent test, skin test, and vancomycin. Additional studies were identified from article reference lists. Relevant, peer-reviewed original research articles and reviews. Neuromuscular blocking agents, natural rubber latex, antibiotics, and induction agents are the most common causes of anaphylaxis during surgical and interventional procedures. Colloids, opioids, and radiocontrast media probably account for less than 10% of all reactions. Newer agents implicated in anaphylaxis include isosulphan blue and chlorhexidine. Skin tests are useful for evaluating allergic reactions to anesthetic agents and penicillins and for selecting alternative agents. Skin testing and specific IgE measurements for latex vary in allergen standardization and sensitivity and specificity, respectively. Flow cytometric allergen stimulation tests show promise in differentiating allergic from idiosyncratic ("pseudoallergic") reactions. Drug desensitization has been shown to be useful for penicillin anaphylaxis. Premedication with histamine receptor antagonists and corticosteroids helps prevent or attenuate radiocontrast media reactions. Anaphylaxis during surgical and interventional procedures may be difficult to evaluate because of the rapid, successive use of multiple drugs or diagnostic agents. Careful analysis of anesthetic records and diagnostic tests for all the putative agents are necessary to ensure a complete evaluation.

Plasma and urinary free 3-nitrotyrosine following cardiac angiography procedures with non-ionic radiocontrast media.

Radiocontrast media (RCM) administration is a common cause of hospital-acquired acute renal failure, especially in high-risk patients, but mechanisms of nephrotoxicity have not been fully elucidated. Reactive oxidant species recently have been shown to play a role in experimental RCM nephropathy, while there is clinical evidence that acetylcysteine, an antioxidant drug, has a protective effect against RCM nephropathy in humans. However, no study has been published showing that RCM administration elicits oxidative stress in humans. In an unselected series of patients undergoing elective cardiac catheterization for coronary artery angiography and/or angioplasty, we monitored the time course of plasma and urinary levels of free 3-nitrotyrosine (3-NT), a stable marker of peroxynitrite generation resulting from the in vivo reaction of superoxide and nitric oxide. Urinary 3-NT levels were measured as the ratio of urinary 3-NT to urinary creatinine. Measurements were taken at baseline, immediately after the procedure and at 24, 48 and 72 h. Twenty-six patients were studied (median age 67.5 years, range 42-86; baseline serum creatinine 1.0 mg/dl, 0.6-1.5; RCM dose 215 ml, 100-580). Plasma 3-NT levels slightly increased over the 72 h following the procedure (P<0.001), while urinary 3-NT levels peaked at the end of the procedure (P<0.001). Urinary 3-NT levels reached at the end of the procedure were proportional to the RCM dose administered (P = 0.017). The present study provides indirect evidence that RCM administration in humans is associated with an increased production of 3-NT. Further studies are needed to ascertain whether oxygen- and nitrogen-derived radical species play a major role in the pathogenesis of RCM-associated nephrotoxicity in the clinical setting.

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.

Provider Use of Preventive Strategies for Radiocontrast Nephropathy in High-Risk Patients

Background/Aims: Radiocontrast nephropathy (RCN) is a common and costly form of acute renal failure. Current preventative strategies include the use of intravenous (IV) fluids and the discontinuation of nephrotoxic medications at the time of radiocontrast administration. We sought to determine whether providers employ these strategies in high-risk patients to limit the development of RCN. Methods: High-risk patients undergoing procedures using radiocontrast media over a 12-month period were identified. Medical records were reviewed for all subjects who developed RCN and a randomly selected 25% of patients without RCN. Patients with a contraindication to IV volume expansion were excluded. Medical records of the remaining patients were reviewed to determine whether IV fluids were administered and whether NSAIDs or COX-2 inhibitors were prescribed at the time of contrast administration. Results: RCN developed in 8% of patients overall. Of 144 patients eligible for IV volume expansion, 16% failed to receive any IV fluids. When IV fluids were employed, their dose and timing of administration varied significantly by treating specialty and procedure. NSAIDs and COX-2 inhibitors were prescribed to 8% of patients. Conclusions: Commonly accepted strategies for the prevention of RCN are underutilized. Quality improvement efforts are needed to increase the use of these two simple prophylactic measures.

Time course of serial cystatin C levels in comparison with serum creatinine after application of radiocontrast media

The delayed increase of creatinine after radiocontrast application is a potential reason for overlooking radiocontrast nephrotoxicity. Cystatin C may be more useful to rapidly assess a decrease in glomerular filtration rate (GFR). We compared cystatin C and creatinine to examine their kinetics after application of radiocontrast media. Forty-one patients (60.8 +/- 8.8 years, 68% males) with normal to subnormal GFR scheduled for coronary angiography (27% with angioplasty), were studied for serum cystatin C and creatinine levels before, 5 h, 24 h and 48 h after angiography. Furthermore, alpha1-microglobulin was checked for evidence of tubular damage. At 5 hours after angiography, there was no significant change compared to baseline in either serum creatinine nor cystatin C. In comparison with the value immediately before coronary angiography, the increase of cystatin C achieved a maximum at 24 h after the application of the contrast agent (+7.2%). Within 48 h, cystatin C decreased to the level before angiography. Serum creatinine increased at 24 h (+7.7%) and continued to increase at 48 h (+11.3%). Cystatin C increases earlier after radiocontrast application compared with creatinine. Therefore, cystatin C needs to be investigated as a potential early marker for nephrotoxicity, especially in the upcoming setting of short-time hospitalizations for coronary angiographies and interventions. Thus, further studies in patients with renal failure undergoing radiocontrast application are warranted to assess the usefulness of cystatin C in respect of an earlier detection of radiocontrast nephrotoxicity.

Hypersensitivity reactions to radiocontrast media: The role of complement activation

Although intravenous use of radiocontrast media (RCM) for a variety of radiographic procedures is generally safe, clinically significant acute hypersensitivity reactions still occur in a significant percentage of patients. The mechanism of these anaphylactoid, or "pseudoallergic," reactions is complex, involving complement activation, direct degranulation of mast cells and basophils, and modulation of enzymes and proteolytic cascades in plasma. In this review, basic information on different RCMs and their reactogenicity is summarized and updated, and the prevalence, pathomechanism, prediction, prevention, treatment, and economic impact of hypersensitivity reactions are discussed. Particular attention is paid to the in vitro and in vivo evidence supporting complement activation as an underlying cause of RCM reactions.

Cyclic AMP reverses radiocontrast media–induced apoptosis in LLC-PK1 cells by activating A kinase/PI3 kinase

Radiographic contrast material is one of agents that are prone to cause nephropathy, although little is known about cellular mechanisms underlying contrast media-induced renal failure. The present study was designed to determine the role of caspase in contrast media-induced renal injury. The modulation by cyclic adenosine monophosphate (cAMP) of cell injury was subsequently examined. LLC-PK1 cells (a proximal renal tubular cell line of porcine origin) were exposed to diverse contrast media for 30 minutes followed by incubation for 24 hours in normal medium. Cell viability was assessed by mitochondrial enzyme activity and propidium iodide stain. Apoptosis was determined by DNA electrophoresis and annexin V stain. Caspase activity was measured fluorometrically. The mRNA for bax and bcl-2 was determined by reverse transcription-polymerase chain reaction (RT-PCR). Iodinated and magnetic resonance contrast media reduced cell viability due to apoptosis. The cell damage induced by a non-ionic contrast medium ioversol was inhibited by specific inhibitors for caspase-3 and -9 but not caspase-8. Ioversol enhanced the activities of caspase-3 and -9, but to a lesser extent, caspase-8. The bax mRNA was enhanced, while bcl-2 mRNA was reduced, after exposure to ioversol. All of these actions of ioversol were reversed by dibutyl cAMP in the manner sensitive to a protein kinase A inhibitor H89 and a phosphatidylinositol 3 (PI3) kinase inhibitor wortmannin. We demonstrated for the first time that cAMP reversed caspase-dependent apoptotic renal cell damage caused by contrast media. Both protein kinase A and PI3 kinase might be involved in protective effect of cAMP.

Anaphylactic transfusion reactions.

Although anaphylactic reactions to blood products are rare, the incidence of allergic reactions to blood products is similar to the allergic reaction incidence to penicillin antibiotics, and therefore worthy of proportionate attention. Comprehensive reviews and guidelines of the management of anaphylaxis currently do not include much information on blood products. Current guidelines for the specific management of anaphylactic transfusion reactions are contradictory as to the utility of anti-IgA testing and incomplete by not offering suggestions for the management of non-IgA related reactions. Anti-IgA is not responsible for most reactions. Anti-haptoglobin antibodies are responsible for more reactions than anti-IgA in Japan, but the cause of most reactions is still not known. The incidence of reactions to platelets is the highest compared with fresh frozen plasma and red blood cells. Pre-storage white blood cell reduction of platelets does not decrease the incidence of reactions, indicating that white blood cell-derived cytokines are not responsible for most reactions. The increased incidence of reactions to platelets compared with fresh frozen plasma suggests that a platelet-related factor may be responsible for many of the reactions. The possible role of platelet microparticles or activated platelet membranes, which carry a negative charge similar to ionic radiocontrast media, the major cause of iatrogenic anaphylactic reactions in the hospital, is explored.

Acetylcysteine for prevention of contrast nephropathy: meta-analysis

Contrast nephropathy is associated with increased in-hospital morbidity and mortality and leads to extension of hospital stay in patients with chronic renal insufficiency. Acetylcysteine seems to be a safe and inexpensive way to reduce contrast nephropathy. We aimed to assess the efficacy of acetylcysteine to prevent contrast nephropathy after administration of radiocontrast media in patients with chronic renal insufficiency. We did a meta-analysis of randomised controlled trials comparing acetylcysteine and hydration with hydration alone for preventing contrast nephropathy in patients with chronic renal insufficiency. The trials were identified through a combined search of the BIOSIS+/RRM, MEDLINE, Web of Science, Current Contents Medizin, and The Cochrane Library Databases. We used incidence of contrast nephropathy 48 h after administration of radiocontrast media as an outcome measure. Seven trials including 805 patients were eligible according to our inclusion criteria and were analysed. Overall incidence of contrast nephropathy varied between 8% and 28%. Since significant heterogeneity was indicated by the Q statistics (p=0.016) we used a random-effects model to combine the data. Compared with periprocedural hydration alone, administration of acetylcysteine and hydration significantly reduced the relative risk of contrast nephropathy by 56% (0.435 [95% CI 0.215-0.879], p=0.02) in patients with chronic renal insufficiency. Meta-regression revealed no significant relation between the relative risk of contrast nephropathy and the volume of radiocontrast media administered or the degree of chronic renal insufficiency before the procedure. Compared with periprocedural hydration alone, acetylcysteine with hydration significantly reduces the risk of contrast nephropathy in patients with chronic renal insufficiency. The relative risk of contrast nephropathy was not related to the amount of radiocontrast media given or to the degree of chronic renal insufficiency before the procedure.

Radiographic contrast media–induced tubular injury: Evaluation of oxidant stress and plasma membrane integrity

Experimental and clinical investigations suggest that oxidant stress is a critical determinant of radiocontrast nephropathy (RCN), and that N acetyl cysteine (NAC) can prevent this damage. This study addresses these issues directly at the tubular cell level. Potential alternative mechanisms for RCN have also been sought. Isolated mouse proximal tubule segments (PTS), or cultured proximal tubule (HK-2) cells, were subjected to radiocontrast media (RCM) (Ioversol, Optiray 320) exposure, followed by assessments of cellular viability [% lactate dehydrogenase (LDH) release, tetrazolium dye (MTT), uptake] and lipid peroxidation. These experiments were conducted in the absence or presence of a variety of antioxidants [NAC, glutathione (GSH), superoxide dismutase, catalase] or pro-oxidant (GSH depletion, heme oxygenase inhibition) strategies. RCM effects on mitochondrial and plasma membrane integrity were also assessed. RCM exposure did not induce PTS lipid peroxidation. Neither antioxidant nor pro-oxidant interventions mitigated or exacerbated RCM-induced tubular cell injury, respectively. RCM impaired mitochondrial integrity, as assessed by ouabain-resistant ATP reductions, and by cytochrome c release (before cell death). RCM also induced plasma membrane damage, as indicated by loss of key resident proteins (NaK-ATPase, caveolin) and by increased susceptibility to phospholipase A2 (PLA2) attack (increase of >/=2 times in free fatty acid and NaK-ATPase release). Hyperosmolality could not account for RCM's toxic effects. RCM toxicity can be dissociated from tubular cell oxidant stress. Alternative mechanisms may include mitochondrial injury/cytochrome c release and plasma membrane damage. The latter results in critical protein loss, as well as a marked increase in plasma membrane susceptibility to exogenous/endogenous PLA2 attack.

Contrast agent-associated nephrotoxicity

Radiocontrast media can lead to a reversible form of acute renal failure that begins soon after the contrast dye administration and generally is benign. Contrast media accounts for 10% of all causes of hospital-acquired acute renal failure and represents the third leading cause of in-hospital renal function deterioration after decreased renal perfusion and postoperative renal insufficiency. The in-hospital mortality rate in patients developing renal insufficiency is related directly to the magnitude increase of serum creatinine concentration. The mortality rate ranges from 3.8% with an increase in serum creatinine level of 0.5 to 0.9 mg/dL to 64% with an increase of greater than 3.0 mg/dL. The mechanism by which contrast-induced renal failure occurs is not well understood. Contrast agent-associated nephrotoxicity appears to be a result of direct contrast-induced renal tubular epithelial cell toxicity and renal medullary ischemia. Furthermore, a key mechanism seems to be alteration in renal dynamics, probably caused by imbalances between vasodilator and vasoconstrictor factors, including the activities of nitric oxide, prostaglandins, endothelin, and reactive oxygen species. The optimal strategy to prevent contrast-associated nephrotoxicity remains uncertain. At present, recommendations are as follows: (1) periprocedural hydration, (2) use of a low-osmolality contrast, and (3) limiting the amount of contrast agent. Recently, considerable interest has resulted from the preliminary positive data on the effectiveness of prophylactic administration of acetylcysteine and fenoldopam. The former may prevent the direct oxidative tissue damage, whereas the latter is a selective intrarenal vasodilator. Copyright 2003, Elsevier Science (USA). All rights reserved.