Nephrotoxicity Of Contrast Media Research Articles

Proteomic Analyses of Contrast Media-Treated Mesangial Cell

Contrast Media is used in angiography, urography and tomography. It has been reported that contrast media nephrotoxicity incidence is 50% higher in patients with diabetic nephropathy undergoing coronary angiography and ap- proximately 15% of these patients developed renal failure. Proteomic analyses are a promising tool to study renal patho- physiology. In the future identification of biomarkers in renal diseases will develop therapeutic targets that will decrease the damage of acute renal failure. To identify proteins that were up or down-regulated in immortalized mesangial cells in a culture in the presence of contrast media we evaluated three groups: control, manitol used as control of osmolarity and Hexabrix TM . The cell homogenate from each group was submitted to the 2D-PAGE analysis, and proteins were identified by MALDI-TOF mass spectrometry. Some proteins were expressed only in the Hexabrix group (Proliferating Cell Nu- clear Antigen and Masp 1); others were up-regulated in the Manitol group (Translationally Controlled Tumor Protein), a protein was expressed only in the Control and Manitol (Annexin A3) groups, and we identified proteins that were ex- pressed in all three groups (Heat shock proteins 27 and 84, protein disulfide isomerase A3 precursor and Beta-actin 1). We believe that other substances present in Hexabrix, possibly the iodine, could be the regulatory factor of these proteins and the Hexabrix could be responsible for the nephrotoxicity observed in these cells.

Efectos renales y sistémicos en la prevención de la nefrotoxicidad por contraste con sueros salino (0,9%) e hiposalino (0,45%)

Physiological and hypotonic saline solutions have been used interchangeably for preventing contrast media nephrotoxicity. No analysis of the possible differential effects of the two solutions on the milieu interieur or intercompartmental fluid volumes has been performed. Our aim was to study the systemic and renal effects of two types of saline solution regularly used to prevent contrast media nephrotoxicity in patients undergoing coronary angiography. Changes in electrolyte levels and volume distribution were studied in 71 individuals who were randomized to receive either 0.9% isotonic saline (n=36) or 0.45% hypotonic saline (n=35) during the 12 hours before and after contrast injection (2000 mL in each period). The creatinine level was elevated equally often in the isotonic and hypotonic saline groups. Isotonic saline administration led to reductions in hemoglobin level, hematocrit and plasma albumin level, and to increases in plasma volume, by 12.3% and 10.4% at 24 and 48 hours, respectively. These changes were significant compared with baseline measurements and compared with the group that received hypotonic saline. Neither of the two saline solutions resulted in a change in plasma atrial natriuretic peptide level. Plasma and urine osmolality decreased only with hypotonic saline. The increase in plasma creatinine level was similar with both isotonic and hypotonic saline. During standard therapy for preventing contrast media nephrotoxicity, (1) isotonic saline, but not hypotonic saline, increased plasma volume; (2) this increase did not raise the atrial natriuretic peptide level; and (3) no difference in the increase in serum creatinine level was observed between the two saline solutions. These findings provide evidence that 0.45% saline, at a dose suitable for preventing contrast media nephrotoxicity, is associated with a lower risk of volume expansion. This result is important for patients with severely impaired ventricular function.

IV N-Acetylcysteine and Emergency CT: Use of Serum Creatinine and Cystatin C as Markers of Radiocontrast Nephrotoxicity

The purpose of this study was to assess the effect of i.v. administration of N-acetylcysteine (NAC) on serum levels of creatinine and cystatin C, two markers of renal function, in patients with renal insufficiency who undergo emergency contrast-enhanced CT. Eighty-seven adult patients with renal insufficiency who underwent emergency CT were randomized to two groups. In the first group, in addition to hydration, patients received a 900-mg injection of NAC 1 hour before and another immediately after injection of iodine contrast medium. Patients in the second group received hydration only. Serum levels of creatinine and cystatin C were measured at admission and on days 2 and 4 after CT. Nephrotoxicity was defined as a 25% or greater increase in serum creatinine or cystatin C concentration from baseline value. A 25% or greater increase in serum creatinine concentration was found in nine (21%) of 43 patients in the control group and in two (5%) of 44 patients in the NAC group (p = 0.026). A 25% or greater increase in serum cystatin C concentration was found in nine (22%) of 40 patients in the control group and in seven (17%) of 41 patients in the NAC group (p = 0.59). On the basis of serum creatinine concentration only, i.v. administration of NAC appears protective against the nephrotoxicity of contrast medium. No effect is found when serum cystatin C concentration is used to assess renal function. The effect of NAC on serum creatinine level remains unclear and may not be related to a renoprotective action.

Significance of zinc in nephrotoxicity of contrast media used in imaging diagnostics of the cardiovascular system

Nephrotoxicity is an undesirable reaction of contrast media used in X-ray or magnetic resonance diagnostics. In addition to a direct toxic effect on renal tubules, the hemodynamic factor is considered to be the main cause of kidney damage and malfunction. The factors that increase the probability of a nephrotoxic effect of contrast media include oldage, diabetes, arterial hypertension, circulatory system insufficiency, neoplastic diseases, and prior kidney damage. Decreased serum zinc is observed in all those conditions. In this article, the influence of contrast media on zinc homeostasis and the possibility of a nephrotoxic reaction caused by these agents is discussed.

A Meta-Analysis of the Renal Safety of Isosmolar Iodixanol Compared With Low-Osmolar Contrast Media

We sought to compare the nephrotoxicity of isosmolar contrast medium (IOCM) iodixanol with low-osmolar contrast media (LOCM) and to identify predictors of contrast-induced nephropathy (CIN). Contrast-induced nephropathy is a serious complication of diagnostic and interventional procedures. Pooled individual patient data (n = 2,727) from 16 double-blind, randomized, controlled trials in which patients received either intra-arterial IOCM iodixanol (n = 1,382) or LOCM (n = 1,345) were included. Patients were stratified according to chronic kidney disease (CKD), diabetes mellitus (DM), or both. Outcome measures were the maximum increase in serum creatinine (Cr) over baseline and the incidence of postprocedural CIN. The maximum Cr increase within 3 days after contrast medium (CM) administration was significantly smaller in the iodixanol group compared with the LOCM group (0.06 mg/dl vs. 0.10 mg/dl, p < 0.001), particularly in patients with CKD (0.07 mg/dl vs. 0.16 mg/dl, p = 0.004) and CKD + DM (0.10 mg/dl vs. 0.33 mg/dl, p = 0.003). Contrast-induced nephropathy, defined as an increase in Cr > or =0.50 mg/dl within 3 days after CM administration, occurred less frequently in the iodixanol group than in the LOCM group in all patients (1.4% vs. 3.5%, p < 0.001), in CKD patients (2.8% vs. 8.4%, p = 0.001), and in CKD + DM patients (3.5% vs. 15.5%, p = 0.003). Independent predictors of CIN included CKD, CKD + DM, and use of LOCM. This meta-analysis of pooled data from 2,727 patients indicates that use of the IOCM iodixanol is associated with smaller rises in Cr and lower rates of CIN than LOCM, especially in patients with CKD or CKD + DM.

Contrast-induced nephropathy: Pharmacological prophylaxis

Contrast media-associated acute renal failure represents the third most common cause of in-hospital renal function deterioration after decreased renal perfusion and post-operative renal insufficiency. Although generally benign, this complication is associated with a mortality rate ranging from 3.8 to 64%, depending on the increase of creatinine concentration. Multiple drugs have been tested in an attempt to prevent this complication. Central to the pathophysiology of contrast-induced nephrotoxicity (CIN) is an alteration in renal hemodynamics. In an effort to reverse these hemodynamic changes, vasodilators and diuretics have been tested as prophylactic drugs. However, their effectiveness has not been confirmed. Recently, considerable interest has resulted from the initial positive data on the effectiveness of prophylactic administration of antioxidant compounds, such as acetylcysteine and ascorbic acid. In this review, we focus on the effectiveness of pharmacologic therapies for preventing CIN.

Néphropathie induite par les produits de contraste iodés, l’épuration extrarénale est-elle efficace en prevention ?

A FREQUENT AND EXPENSIVE PROBLEM: Ninety percent of contrast media nephrotoxicity (CMN) occur in patients with pre-existing kidney failure. Its aggravation may require early chronic dialysis. CMN prophylaxis is important in these patients. Pre- and post-hydration, with infusion of isotonic saline solution or sodium bicarbonate, and reduction of contrast medium (CM) volume to the strict minimum are essential for preventing CM-induced kidney failure. THE INTEREST OF PROPHYLACTIC HEMODIALYSIS AND HEMOFILTRATION: An interesting approach in preventing CMN is the early elimination of the CM with dialysis techniques. Preventive hemodialysis does not reduce the risk of CMN, but hemofiltration has shown significant efficacy in a population of patients with kidney failure. THE INTEREST OF IMMEDIATE HEMODIALYSIS IN CHRONIC HEMODIALYSIS PATIENTS: Although nephrotoxicity is no longer a problem in patients undergoing chronic hemodialysis, CM, especially in high-dose injections, may be responsible for fluid and electrolyte abnormalities and/or volemic expansion. No data yet justify a conclusion that a hemodialysis session immediately after injection of a CM in chronic dialysis patients might be helpful.

Effects of contrast media on renal function in patients with cirrhosis: a prospective study.

Patients with cirrhosis are frequently submitted to radiological procedures that require the administration of contrast media. Contrast media is a well-known cause of renal failure, particularly in the presence of some predisposing conditions. However, it is not known whether cirrhosis constitutes a risk factor for contrast media-induced renal failure. The aim of this study was to assess the possible nephrotoxicity of contrast media in patients with cirrhosis. In a first protocol, renal function was evaluated with sensitive methods (glomerular filtration rate using iothalamate I 125 clearance and renal plasma flow using iodohippurate I 131 clearance) before and 48 hours after the administration of contrast media in 31 patients with cirrhosis (20 with ascites, 5 with renal failure). Solute-free water clearance, urine sodium, prostaglandins, and markers of tubular damage were also measured. The administration of contrast media was not associated with significant changes in renal function tests, neither in the whole group of patients nor in patients with ascites or renal failure. Urinary prostaglandin E2 and N-acetyl-beta-D-glucosaminidase increased significantly, but sodium and solute-free water excretion remained unchanged. In a second protocol, a different series of 60 patients with cirrhosis and renal failure were examined prospectively. No patient had renal failure due to contrast media. Only in 1 patient with septic shock was contrast media a possible contributing factor. In conclusion, the administration of contrast media is not associated with adverse effects on renal function in patients with cirrhosis. Cirrhosis does not appear to be a risk factor for the development of contrast media-induced nephrotoxicity.

Contrast media augmented apoptosis of cultured renal mesangial, tubular, epithelial, endothelial, and hepatic cells.

Nephrotoxicity of contrast media, resulting in apoptosis and acute necrosis of tubular cells, is well documented. No studies concerning mesangial cells apoptosis have been published yet. Apoptosis of cultured mesangial, tubular, and hepatic cell lines was investigated following exposure to different contrast media. Apoptosis was assessed by TUNEL assay and verified by Mayer Hematoxylin staining. Iopromide, Ioxaglate, and Ioxatalamate induced apoptosis in all cell cultures at final concentrations ranged from 0.1% to 10.0%. However, only 1% to 10% Iomeprol elicited a significant apoptosis. Moreover, at 10% concentration, Iomeprol induced significantly less apoptosis than Iopromide, Ioxaglate, or Ioxatalamate. First, Iomeprol, which has a different physico-chemical properties, proved to be less proapoptotic compared with other contrast compounds. Second, all types of cells similarly respond by apoptosis to contrast media induced injury. However, apoptosis of mesangial cells might generate additional deleterious effects in vivo.

Angiography for renal artery stenosis: no additional impairment of renal function by angioplasty

The aim of this study was to compare renal function between patients with renal angiography and patients with renal angiography and angioplasty (AP) for renal artery stenosis (RAS). Forty-seven patients with suspected RAS were prospectively investigated by digital subtraction angiography (DSA) using non-ionic low osmolar contrast media (CM). In 22 patients RAS was detected and in 16 cases an angioplasty was performed in the same session. The following parameters were determined 1 day prior to and after the DSA, respectively: serum creatinine (S-Crea, micromol/l) and single-shot inulin clearance (In-Cl, ml/min) for the evaluation of renal function; and urine alpha 1-microglobuline (AMG, microg/g Crea) and beta-N-acetyl-glucoseaminidase (beta-NAG, U/g Crea) as markers of tubular toxicity. Serum creatinine was measured additionally 2 days after CM had been injected. In both groups with and without AP 174+/-65 and 104+/-56 ml of CM ( p<0.0005) were used, respectively. There were no differences with regard to renal function or risk factors for CM nephrotoxicity between both groups. In the group with AP S-Crea and In-Cl (each: mean+/-SD) did not change significantly (before DSA: 171+/-158 and 61+/-24, after DSA: 189+/-177 and 61+/-25, respectively), beta-NAG (median) rose from 4 to 14 ( p<0.05) and AMG from 8 to 55 (n.s., because of high SD). In the group without AP S-Crea increased from 134+/-109 to 141+/-113 ( p<0.01), In-Cl dropped from 65+/-26 to 62+/-26 ( p<0,01), beta NAG (median) rose from 4 to 8 ( p=0.01), and AMG from 7 to 10 (n.s.). A rise in baseline S-Crea by more than 25% or 44 micromol/l occurred in 4 and 2 patients in the group with and without AP, respectively. Creatinine increase was reversible in all cases within 7 days. In this study using sensitive methods to detect changes of renal function and tubular toxicity no additional renal function impairment in DSA with angioplasty for RAS compared with DSA alone could be demonstrated. Our data suggest that AP performed for RAS has a beneficial effect on renal function.

Editorial

In this Supplement, many of the recent advances in imaging and intervention in the urinary and male genital tracts are described and illustrated. The newer iodinated contrast media are described and the current understanding of their nephrotoxic effects and of how to prevent contrast medium nephrotoxicity are reviewed. Ultrasonographic contrast media are as yet little used in the urinary tract in clinical practice, but their considerable potential for the future is outlined. The improvements in renal CT diagnosis provided by helical (spiral) technology are described in several reviews, particularly in the evaluation of renal masses and for the diagnosis of ureteric colic, renal artery stenosis and acute pyelonephritis. The reviews show how, in addition to its role in diagnosis, CT has provided new insights into the pathophysiology of renal infection and acute ureteric obstruction. Doppler ultrasonography has also given new information about the pathophysiology of acute ureteric obstruction by allowing quantitative evaluation of the reduction in flow in the intrarenal arteries. However, the current consensus is that ultrasonographic imaging and Doppler studies have a secondary role in the diagnosis of acute ureteric obstruction. Improved MRI techniques now provide resolution rivalling CT for the diagnosis of renal masses and the multiplanar images are particularly helpful for staging renal cell carcinoma. The ability of MRI to detect static fluid in dilated pelvicalyceal systems and ureters without the use of contrast media provides a new noninvasive method for diagnosing ureteric obstruction. MR angiography has advanced and now rivals CT for the diagnosis of renal artery stenosis. The current role of nuclear medicine studies in the urinary tract and the imaging approach to childhood urinary tract infection are thoughtfully reviewed. The role of imaging in staging bladder and prostate cancer is outlined, with the emphasis on the value of MRI in assessing pelvic tumours because of its multiplanar images and excellent soft-tissue contrast resolution. The specific detection of prostate cancer using radionuclide labelled antibodies is described. The detailed images of the scrotal contents provided by modern high-resolution ultrasonography and their role in scrotal diagnosis are illustrated and the wide range of abnormalities which can be detected by ultrasonography and MR in infertile men is reviewed. CT and MRI can now accurately characterize many adrenal masses. The imaging approach to the incidentally discovered adrenal mass is described. Intervention in the urinary tract from simple to complex is reviewed and there is a look to the future in the article on interventional MR. The technical achievement summarized in this Supplement is certainly impressive but it is important not to be seduced either by the glamour of the new technology or the aesthetic appeal of the resultant images. Our primary purpose must be to obtain images which are necessary for decisions about patient management and to provide interventions which improve patient outcome. Therefore, the challenge for the future is not just to continue developing the new techniques, but for radiologists and urologists to work together to establish how the new methods should be used to achieve the best and most cost-effective imaging and interventional strategies to solve particular clinical problems. Guest Editor

An Evaluation of the Nephrotoxic Effects of Nonionic Low Osmolality Contrast Media Using Urinary Enzymes

A prospective clinical study was conducted to examine the usefulness of urinary enzymes as a sensitive parameter for determining nephrotoxicity caused by LOCM. Forty-seven patients were intravenously injected with 100 ml of LOCM (iohexol or iopamidol) in radiographic studies. Serum creatinine and creatinine clearance (Ccr) were determined before and 7 days after LOCM infusion. Urinary excretion of N-acetyl-β-D-glucosaminidase (NAG) and γ-glutamyltransferase (γ-GTP) was determined before and 1, 2, 3 and 7 days after LOCM administration. To analyze the relationship between the nephrotoxic effect of LOCM and renal function, patients were divided into group L (Ccr<70 ml/min, n = 19) and group N (Ccr≥70 ml/min, n = 28). No significant changes were noted in serum creatinine or Ccr in either group. Urinary NAG and γ-GTP levels were significantly elevated on day 1 compared with the levels prior to LOCM infusion, but these returned to the base line after day 2. The increase ratio of urinary NAG in group L was significantly higher than that in group N on days 3 and 7. No statistical difference between groups L and N was observed regarding urinary γ-GTP increases on any of the days. In conclusion, urinary enzymes are sensitive and useful indicators for evaluating contrast media nephrotoxicity, which cannot be detected by serum creatinine or Ccr. Careful attention should be paid in radiographic studies to patients with renal dysfunction, even when LOCM is being employed.

Oxygen free radicals and contrast nephropathy

Ionic, high-osmolality contrast medium causes nephrotoxicity associated with increased intrarenal adenosine production. To test the hypothesis that oxygen free radicals (produced during intrarenal adenosine catabolism to xanthine) should be implicated in the pathogenesis of ionic, high-osmolality contrast medium nephrotoxicity in humans and to determine whether magnesium protects the kidney from oxygen free radical injury following contrast, 39 patients with mild renal dysfunction were divided into low (LoMg++) and normal (NlMg++) magnesium states and randomized to precoronary angiography oral allopurinol (a xanthine oxidase inhibitor) or placebo. Creatinine clearance and urinary xanthine excretion were measured before and after angiography. Forty-eight hours after contrast medium exposure, placebo- treated LoMg++ and NlMg++ patients had 61%+/-5% and 67%+/-6% increases in urinary xanthine excretion, respectively; however, placebo-treated LoMg++ patients had a greater (79%+/-9% v 35%+/-6%; P < 0.01) decrease in creatinine clearance than placebo-treated NlMg++ patients. Allopurinol-treated LoMg++ and NlMg++ patients had no significant change in urinary xanthine excretion, but did have 40%+/-7% and 33%+/- 5% decreases, respectively, in creatinine clearance 48 hours after contrast medium exposure. There was no difference in renal dysfunctional response among placebo-treated NlMg++ patients or allopurinol-treated LoMg++ or NlMg++ patients. These data suggest (1) that oxygen free radicals contribute to ionic, high-osmolality contrast medium nephrotoxicity in hypomagnesemic patients with mild renal disease and (2) that magnesium attenuates the nephrotoxicity mediated by oxygen free radicals. (Am J Kidney Dis 1998 Jul;32(1):64-71)

Contrast media-induced nephrotoxicity--questions and answers.

The intravascular administration of contrast media (CM) can produce acute haemodynamic changes in the kidney characterized by an increase in renal vascular resistance and a decrease in the glomerular filtration rate (GFR). These changes may lead to clinically significant reduction in renal function in patients with pre-existing risk factors such as diabetic nephropathy, congestive heart failure and dehydration. The pathophysiology of the renal haemodynamic effects of CM involves activation of the tubuloglomerular feedback (TGF) mechanism and the modulation of the intrarenal production of vasoactive mediators such as prostaglandins, nitric oxide, endothelin and adenosine. The TGF response is osmolality-dependent and accounts for about 50% of the acute functional effects of high osmolar CM on the kidney. Reduction in the synthesis of the endogenous vasodilators nitric oxide and prostaglandins increases the nephrotoxicity of CM. Endothelin and adenosine play a crucial role in mediating the acute functional effects of CM. Antagonists of these mediators attenuate the reduction in renal function induced by contrast agents. Vacuolization of the cells of the proximal tubules and necrosis of those of the medullary ascending limbs of loops of Henle are the main structural effects of CM in the kidney. The reduction in renal function induced by CM could be minimized by the use of low osmolar CM and adequate hydration. The prophylactic administration of calcium channel blockers and adenosine antagonists such as theophylline may also offer some protective effect.

Contrast nephrotoxicity: Predictive value of urinary enzyme markers in a rat model

We tested whether urinary enzymes are an accurate and useful marker of renal damage in a rat model of contrast media nephrotoxicity. Thirty rats were pretreated with a combination of salt depletion, indomethacin, and contrast material. Alanine aminopeptidase (AAP), gamma-glutamyltranspeptidase (GGT), and N-acetyl-beta-D-glucosaminidase (NAG) were measured before and 24 hr after injection of contrast material. Enzyme concentrations were correlated with glomerular filtration rate (GFR) and histology. Decreasing GFR and histopathologic changes were found only in rats treated with all three variables. NAG levels increased from baseline for both diatrizoate meglumine- and ioversol-treated animals (from 83.9 +/- 48.6 to 145.5 +/- 55.4 and from 69.41 +/- 43.6 to 123.1 +/- 50.7, respectively; P < 0.05 from baseline for ioversol) and declined in other groups. GGT and AAP levels did not correlate well with structural and functional changes. In this model of contrast nephrotoxicity, NAG concentration appears to correlate with structural and functional changes associated with contrast media nephrotoxicity. However, the large range of baseline values makes this of dubious clinical use. AAP and GGT levels appear less helpful in detecting renal damage.

Low-Osmolality Contrast Media and the Risk of Contrast-Associated Nephrotoxicity

The authors review clinical data, including those from the recent Iohexol Cooperative Group trial, regarding the nephrotoxic potential of low-osmolar versus high-osmolar contrast media. The clinical characteristics and postulated mechanisms of contrast-associated nephrotoxicity are also considered. The principal strategy for identifying relevant articles was to search the MEDLINE database using the MeSH heading "contrast media nephrotoxicity." Articles from 1966 through 1992 that were considered included original research papers as well as reviews. Those articles selected for detailed review documented original research pertaining to use of low-osmolar or high-osmolar agents. Selected abstracts for pertinent society meetings were also used. No attempt was made to be complete in describing the field. Rather, specific articles that selectively address the question of nephrotoxicity related to the osmolar content of contrast media were used for discussion. In-vitro and animal studies indicate that renal changes possibly involved in the pathogenesis of contrast-associated nephrotoxicity seem to be ameliorated with low-osmolar contrast media, compared with high-osmolar agents. Several recent clinical trials, as well as a meta-analysis combining 24 randomized studies, suggest that the risk of contrast-associated nephrotoxicity is similarly low with high-osmolar and low-osmolar agents among otherwise stable patients with normal renal function, but that low-osmolar contrast is less nephrotoxic than media with high osmolality in patients with pre-existing renal insufficiency.

Nephrotoxicity of contrast media in persons over the age of 60

The nephrotoxicity potential and differences of three different contrast media, a high osmolar ionic (Diatrizoate), a low osmolar ionic (Ioxaglate) and a low osmolar non-ionic (Iohexol) after intravenous administration in 84 non-diabetic patients with normal renal function (26 female, 58 male) submitted to digital vascular imaging, were investigated.

Modulation of the Renal Effects of Contrast Media by Endothelium-Derived Nitric Oxide in the Rat

A possible involvement of endothelium derived relaxing nitric oxide (NO) in the pathogenesis of iodinated contrast media (CM)-induced nephrotoxicity was investigated in the rat. Male rats (6 to 12 per group) were uninephrectomized. Six days later, the aorta was clamped above the renal artery and a low-osmolar contrast medium (CM), ioxaglate, was injected (1 mL/min; 3 minutes) via an aortic puncture in the single remaining kidney. Contrast medium was injected with or without the NO-synthase inhibitor L-NAME (100 mg/kg intravenously [i.v.] 5 minutes before CM). One group received L-Arginine, the physiological precursor of NO (100 mg/kg i.v.), 5 minutes before L-NAME. Phenylephrine (300 micrograms/kg; 30 min) was used as a vasoconstrictive NO-independent control. The effects of iohexol, another low-osmolar CM, on creatinine clearance (CrCl) were also studied with and without pretreatment with L-NAME. A control group was subjected to a 3-minute renal ischemia only. Creatinine clearance and urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion were determined before, and 24 and 48 hours after CM administration. Blinded histologic analysis was carried out after completion of the study. When administered alone, neither L-NAME nor L-arginine modified CrCl. Ioxaglate mildly but significantly decreased CrCl at 24 hours (-26.5% of preinjection value). This was similar to the effect observed in the control group subjected to ischemia only. When associated with L-NAME, ioxaglate markedly decreased CrCl (-58 + 11% at 24 hours, P < .05 vs. ioxaglate alone). A similar interaction was noted in the case of iohexol. L-NAME also markedly increased ioxaglate-induced urinary NAG excretion. Phenylephrine had a similar impact on renal function. L-arginine pretreatment reduced the increase in serum creatinine induced by L-NAME+ioxaglate (68 + 17 mumol/L vs. 175 + 59 mumol/L for L-NAME+ioxaglate; P < .05) and urinary NAG excretion. Ioxaglate alone induced only tubular epithelial vacuolization. When associated with L-NAME, this CM induced tubular and vascular lesions, as well as necrosis in the outer medulla. Such histologic effects were clearly inhibited by L-arginine. These data indicate that L-NAME, a specific inhibitor of NO-synthase, and phenylephrine, accentuate the nephrotoxicity of CM in the rat. This is consistent with results from the literature showing that CM-toxicity is enhanced by renal ischemia.

Nephrotoxicity of contrast media following cardiac angiography: pathogenesis, clinical course, and preventive measures, including the role of low-osmolality contrast media.

To review the incidence, definition, clinical course, risk factors, pathogenesis and prevention of contrast-associated nephropathy (CAN) following cardiac angiography with emphasis on differences between high-osmolality contrast media (HOCM) and low-osmolality contrast media (LOCM). Investigations in animal models and in patients following cardiac angiography. Animal models of the pathogenesis of CAN are presented. Human studies describing the incidence, clinical course, risk factors, and prevention of CAN are reviewed. Comparative clinical trials of HOCM (diatrizoate, metrizoate) and LOCM (iohexol, iopamidol, ioxaglate) nephrotoxicity following cardiac angiography are critically evaluated. All clinical studies comparing CAN of HOCM versus LOCM following cardiac angiography have some methodologic limitations (e.g., small sample size, lack of control for other factors) that may affect renal function, lack of stratification for other reported risk factors, and variable or short follow-up periods. Whether the incidence of CAN following cardiac angiography is reduced with LOCM remains controversial. The incidence of CAN in patients with normal renal function does not appear to differ in patients treated with LOCM versus HOCM because few patients in each group develop renal failure. Additional controlled clinical trials comparing CAN of LOCM and HOCM in patients with renal dysfunction are needed. Because of greater product cost and scarcity of documented benefit compared with HOCM, selection of LOCM based on the presence of renal dysfunction cannot be recommended at this time.

Nephrotoxicity of Contrast Media in High-Risk Patients with Renal Insufficiency: Comparison of Low- and High-Osmolar Contrast Agents

We have compared the renal effects of ioxitalamate, ioxaglate, and iopamidol in patients with chronic renal failure. Sixty consecutive patients with an estimated creatinine clearance (ECRCl) less than 60 ml/min were randomly assigned to receive either ioxitalamate, iopamidol, or ioxaglate. All patients received 500 cm3 isotonic saline before the procedure. Serum creatinine and ECRCl were estimated before, 1 and 2 or 3 days after the procedure. There was no statistical difference between the three groups with respect to age, sex, weight, renal function, amount of iodine, and type of procedure. Mean serum creatinine and ECRCl remained unchanged after administration of contrast media. No patient had nephrotoxicity or acute oliguria requiring dialysis as a result of the administration of contrast material. The number of patients with an increase in the serum creatinine level greater than 10% from the basal value did not differ in the treatment groups. The maximal increases in serum creatinine were 52 mumol/l (29%) in the ioxitalamate group, 56 mumol/l (18%) in the ioxaglate group, and 57 mumol/l (23%) in the iopamidol group (p = NS). Using a population carefully randomized and matched for renal insufficiency, we could not show any differences in nephrotoxicity between these three contrast agents. Clinically serious renal impairment was uncommon in our study, regardless of the contrast agent used. However, the interpretation of these favorable findings requires a cautionary note. All patients in this study were well hydrated before and after uro-/angiography, and none had a recent renal injury or a treatment with a nephrotoxic agent that would predispose to injury from contrast material.(ABSTRACT TRUNCATED AT 250 WORDS)