The role of osmolality in the incidence of contrast-induced nephropathy: a systematic review of angiographic contrast media in high risk patients

BACKGROUND: The role of osmolality of contrast media (CM) in the pathogenesis of contrast-induced nephropathy (CIN) has been suggested by studies comparing high osmolality CM (>1500 mOsm/kg) with low-osmolality CM (550-850 mOsm/kg), and by the results of a recent comparison of a CM isotonic to plasma (iodixanol, 290 mOsm/kg) with a low-osmolality CM (iohexol, 844 mOsm/kg) in high-risk patients undergoing cardiac or peripheral angiography. METHODS: Using prospectively defined search criteria, we performed a systematic overview of prospective, randomized, controlled studies of CIN in renally impaired patients receiving intra-arterial doses of iodixanol or low-osmolality, nonionic CM, and conducted a systematic review of the data from those studies to determine whether the osmolality of CM was predictive of CIN incidence. RESULTS: Seventeen primary studies met the selection criteria, for a total of 1365 patients. Overall, the incidence of CIN was 16.8%. A multivariate logistic regression model showed that the risk of CIN is similar with the iso-osmolality iodixanol and the low-osmolality iopamidol (796 mOsm/kg). The risk of CIN was significantly lower with iodixanol and iopamidol compared to iohexol. The incidence of CIN with iohexol was also significantly higher than with iopamidol, despite their similar osmolalities. CONCLUSION: These data suggest that factors other than osmolality play a significant role in the pathogenesis of CIN, at least for agents with osmolalities of 800 mOsm/kg or less.     

Renal failure in 57 925 patients undergoing coronary procedures using iso-osmolar or low-osmolar contrast media

We compared the Swedish Coronary Angiography and Angioplasty Registry with the Swedish 'Hospital Discharge Register' to assess contrast media (CM)-induced renal failure. Hospitals used only one type CM. From 2000 to 2003, iodixanol (iso-osmolar) was used in 45 485 patients, ioxaglate (low osmolar) in 12 440 subjects. To include the earlier used CM iohexol (low osmolar), analysis extended back to 1990 (86 334 patients). Incidence of clinically significant renal failure was greatest for patients receiving the iso-osmolar CM iodixanol (1.7%). Ioxaglate-treated patients had a significantly lower renal failure incidence (0.8%, P<0.001). The odds ratio for iodixanol-treated patients was significantly higher than for ioxaglate (1 vs 0.48, P<0.001). In subsets of either diabetic patients or patients with previous renal failure, odds ratios for renal failure remained greater in the iodixanol groups (P<0.01). Hospitals switching CM to iodixanol experienced a doubling in clinically significant renal failure after cardiac procedures. Dialysis was required in 0.2% of patients receiving iodixanol, which was significantly higher (P<0.01) than for ioxaglate-treated patients (0.1%). Iohexol-treated patients had a similar low risk for developing clinically significant renal failure (0.9%) as ioxaglate. In conclusion, risk of developing renal failure and required dialysis after coronary procedures is higher when patients received iodixanol than ioxaglate or iohexol.     

Nephrotoxicity of low-osmolality versus iso-osmolality contrast agents: impact of N-acetylcysteine

BACKGROUND: Recent data support that iodixanol, an iso-osmolality contrast agent, is less nephrotoxic than low-osmolality contrast agents when hydration is the only prophylactic strategy used. We evaluated the nephrotoxicity of iso- and low-osmolality contrast agents with prophylactic administration of N-acetylcysteine (NAC) along with hydration. METHODS: Two hundred and twenty-five patients with chronic renal insufficiency (serum creatinine >1.5 mg/dL or an estimated glomerular filtration rate <60 mL/min/1.73 m(2)), referred to our institution for coronary and/or peripheral procedures, were assigned to receive low-osmolality (iobitridol group; N = 115) or iso-osmolality (iodixanol group; N = 110) contrast dye. In all cases prophylactic administration of 0.45% saline intravenously and NAC (1200 mg orally twice daily) was used. RESULTS: Baseline creatinine levels were similar in the 2 groups [iobitridol group = 1.70 (IQR: 1.54-1.98) mg/dL; iodixanol group = 1.73 (IQR: 1.56-2.00) mg/dL, P = 0.33]. The risk score for contrast nephrotoxicity was 5.0 +/- 1.6 in the iobitridol group versus 5.0 +/- 1.8 in the iodixanol group (P = 0.44). Increase of at least 0.5 mg/dL of the creatinine concentration 48 hours after the procedure occurred in 4/115 patients (3.5%) in the iobitridol group and 3/110 patients (2.7%) in the iodixanol group (P = 1.00; OR 0.78; 95% CI 0.17-3.56). Amount of contrast media administration was similar in the 2 groups (iobitridol group = 167 +/- 90 mL; iodixanol group = 164 +/- 82 mL; P = 0.61). CONCLUSION: Nephrotoxicity of iso-osmolality and low-osmolality contrast agents was similar when a prophylactic strategy of hydration plus NAC was utilized.     

Nephrotoxicity of iodixanol versus iopamidol in patients undergoing peripheral angiography with or without endovascular therapy

Purpose

To compare the nephrotoxic effects of iodixanol and iopamidol in patients undergoing peripheral angiography.

Methods

Patients scheduled for peripheral angiography were randomly assigned to the iodixanol group (n?=?463) and iopamidol group (n?=?458). The primary endpoint was the incidence of contrast associated acute kidney injury (CA-AKI), which was defined as an increase?≥?25% or ≥?44.2 µmol/l (0.5 mg/dl) in serum creatinine (SCr) from baseline within 72 h after receiving contrast media (CM). The secondary endpoints were the mean peak SCr increase within 72 h after receiving CM and major adverse renal events (SCr increased by two times after 30 days, the need for dialysis treatment, rehospitalization for acute renal failure, or kidney-related death) during hospitalization and within 30 day postdischarge.

Results

The incidence of CA-AKI did not differ significantly between the iodixanol group and iopamidol group (18.1% vs. 16.8%; p?=?0.595). There was no significant difference in the mean peak SCr increase between the iodixanol group and iopamidol group (10.4?±?13.0 vs. 10.6?±?14.3 µmol/l, p?=?0.919). There were four patients [1 (0.2%) patient in the iodixanol group and 1 (0.7%) patients in the iopamidol group, p?=?0.609] with doubling of SCr; no other adverse renal events were observed.

Conclusions

Our data showed that the nephrotoxicity of iodixanol was comparable with that of iopamidol in patients undergoing peripheral angiography.

     

Nephrotoxic effects of ionic and nonionic contrast media on rat and human renal cortical slices

Background. Nephrotoxicity is a well-known adverse effect of radiographic contrast medium (CM). Recently, several kinds of low- osmolality nonionic CM have been developed. However, the nephrotoxic effects of nonionic CM compared with those of ionic CM have not been well evaluated. Methods. To compare the direct nephrotoxic effects of ionic and nonionic CM on renal epithelial cells, rat and human renal cortical slices were incubated with CM at 37°C for 120 min. Diatrizoate and iothalamate were employed as ionic CM. Iopamidol, iohexol, iomeprol, ioversol, iopromide, and ioxilan were employed as nonionic CM. Direct toxicity of CM was evaluated by the activities of N-acetyl-β-D-glucosaminidase (NAG) and γ-glutamyl-transferase (GGT) released from the renal slices into the incubation buffer. Results. In the experiment with rat renal slices, NAG and GGT activities in buffer solutions were increased dose-dependently by 30, 60, and 90 mg I/ml of CM. There was no significant difference in NAG or GGT release between ionic and nonionic CM at the concentration of 60 mg I/ml. In the experiment with human renal slices, incubation with 60 mg I/ml of diatrizoate, iothalamate, iomeprol, and iopromide did not affect NAG levels. Significantly greater increases in NAG levels, compared with the control, were observed after incubation with iopamidol, iohexol, ioxilan and ioversol. Nevertheless, the increases in NAG caused by some of the nonionic CM were very slight. GGT release from human renal slices was significantly greater than that of the control in all experimental groups. Again, there was no significant difference in renal toxicity between ionic and nonionic CM. Conclusions. Newly developed nonionic CM had almost the same degree of nephrotoxicity against rat and human renal epithelial cells as conventional ionic CM, when direct renal toxicity was evaluated by enzyme release in an in-vitro experimental system using renal cortical slices. Received: November 22, 2000 / Accepted: March 6, 2001     

Assessing residual renal function and efficiency of hemodialysis--an application for urographic contrast media

BACKGROUND: In patients on hemodialysis with end-stage renal disease there is an increasing interest in measuring both residual renal function (RRF) and quantity and quality of dialysis because insufficient dialysis gives higher mortality. For that purpose we have measured clearances of two urographic iodine (I) contrast media (CM) with different molecular masses (iohexol 821 u and iodixanol 1, 550 u). These CM are filtered through glomeruli and dialysis membranes and have higher molecular masses than urea and creatinine and might represent the dialyzability of the hypothetic uremic toxins with a molecular mass of 300-5,000 u. METHODS: Thirteen patients (8 of them were anuric) immediately after hemodialysis received 15 ml iohexol (300 mg I/ml i.v.) and 2 weeks later in the same way 15 ml iodixanol (320 mg I/ml). Nine other patients (2 anuric) received CM after only one dialysis; 8 got iohexol and 1 got iodixanol. After the CM injections the iodine concentrations were measured with X-ray fluorescence in blood and, when available, urine during the following 2 days including both the start and end of the next dialysis. Eighteen patients after two dialysis sessions, 2 weeks apart, received 10 ml iohexol i.v., and a single blood sample was taken at the start of the next dialysis 2 days later to determine RRF alone. RESULTS: In the 10 anuric patients the extrarenal clearances (mean +/- SD) were 2.5 +/- 1.1 and 2.7 +/- 1.1 ml/min/1.73 m(2) for iohexol and iodixanol, respectively. In patients with RRF good correlations were demonstrated between body clearance, based on two blood samples, and renal clearance of CM. Good correlations (r(2) = 0.853 for iohexol, r(2) = 0.933 for iodixanol) were noted between two-sample and single-sample body clearances. Repeated single sample iohexol clearances gave a coefficient of variation of 15%. During dialysis the clearances of iohexol and iodixanol were, respectively, 69 +/- 16 and 58 +/- 11 ml/min/1.73 m(2) when calculated from a single-pool model (hemodialysis clearance of CM from plasma). A median increase (rebound) of CM concentrations in plasma 45 min dialysis was 8% for iodixanol and 18% for iohexol. When the CM concentration 45 min after dialysis was used, the clearance values were by 8-10% lower and represented the hemodialysis clearance of CM from the extracellular compartments. The dialysis eliminations of iohexol and iodixanol were similar to that of urea, measured as percentage reduction of serum levels during dialysis. CONCLUSIONS: A single injection of CM at the end of dialysis followed by a single blood sample at the start of the next dialysis gives total body clearance, i.e., an estimation of the RRF. An additional blood sample at the end of the next dialysis gives dialysis efficiency.     

Effect of haemodialysis after contrast medium administration in patients with renal insufficiency

Background. The study was designed to investigate the influence of haemodialysis on the pharmacokinetics of the non-ionic contrast medium iopentol and the outcome of radiocontrast nephropathy in patients at risk undergoing angiography. Methods. We prospectively studied 30 patients with reduced renal function (mean serum creatinine concentration (±SEM), 2.4±0.16 mg/dl (212±14 &mgr;mol/l)). Patients were randomly assigned to receive either a haemodialysis procedure for 3 h, started as soon as possible (63±6 min) after administration of contrast medium, or a conservative treatment. Serum concentration of iopentol and creatinine were followed for up to 14 days. Results. The extracorporeal plasma clearance of contrast medium was 71±2.5 ml/min. The fraction of the dose eliminated was 32±3%. The rate of radiocontrast nephropathy (defined as serum creatinine increase of ⩾0.5 mg/dl (44 &mgr;mol/l) within 48 h) after administration of contrast medium was similar in both groups (53 and 40% in group 1 (haemodialysis) and group 2 (conservative treatment) respectively). The course of absolute changes in serum creatinine over the whole observation period was not different in both groups. Conclusions. The data indicate that haemodialysis eliminates contrast medium effectively, but it may not influence the incidence or outcome of contrast induced nephropathy.     

Comparison between gadolinium and iodine contrast for percutaneous intervention in atherosclerotic renal artery stenosis: clinical outcomes

Background. Percutaneous angiography with iodinated contrastin patients with chronic kidney disease carries a risk of contrastnephropathy, which is independently associated with renal diseaseprogression and increased mortality. Gadolinium contrast isa potential alternative to iodinated contrast for percutaneoustransluminal renal angioplasty (PTRA), and appears to be safeand well tolerated. The aim of this study was to assess theresults of gadolinium use to facilitate PTRA in patients withchronic kidney disease. Methods. Clinical outcomes were compared between patients withserum creatinine (Cr) 176 µmol/L (2 mg/dL), who had eithergadolinium (n = 57; gadoteridol or gadodiamide), iodinated (n= 68; iohexol or iodixanol) or a combination of gadolinium andiodinated-contrast-enhanced (n = 38) PTRA. Results. Despite similar degrees of pre-procedural renal insufficiency,the incidence of immediate contrast nephropathy [defined asan increase in serum Cr of 44 µmol/L (0.5 mg/dL) within7 days without other identifiable causes] was lowest in thegadolinium group (3/57, 5.3%) compared to those receiving acombination of modest iodinated contrast in addition to gadolinium(4/38, 10.5%) or solely iodinated contrast (14/68, 20.6%). Thiswas associated with a reduction in the 30-day progression toneed for renal replacement therapy (RRT) (P < 0.005). Yet,over a mean follow-up of 40 ± 22 months, renal functionoutcomes or all-cause mortality were not different between thecontrast groups. The type of contrast used had no effect ontechnical success and both short- and long-term blood pressureoutcomes were comparable between the groups. Two patients developedpathology-proven nephrogenic fibrosing dermopathy, a seriousskin condition that has been seen in patients with kidney diseasefollowing administration of gadolinium. Conclusions. Gadolinium contrast appears to be an effectiveagent for interventional renal angiograms. Compared to iodinatedcontrast, gadolinium contrast is associated with a significantlylower incidence of contrast nephropathy and early progressionto end-stage renal disease (ESRD) in patients with pre-existingchronic kidney disease. The risk of fibrosing dermopathy howeverand remains to be established.     

The Effects of the Iodinated X-Ray Contrast Media Iodixanol,Iohexol, Iopromide,and Ioversol on the Rat Kidney Epithelial Cell Line NRK 52-E

Nephrotoxicity, associated with the administration of iodinated X-ray contrast media (ICM), continues to be a major side effect in a significant number of vulnerable patients undergoing diagnostic X-ray imaging procedures. The molecular mechanisms underlying these adverse effects on the kidneys are unclear despite several decades of investigation. Side effects are more common after exposure to high-osmolar compared with low-osmolar ICM, suggesting that osmolality may be an important physical–chemical property related to nephrotoxicity. This investigation in cultured NRK 52-E cells, a cell line of renal origin, compares the in vitro toxicity of the iso-osmolal ICM iodixanol with the low-osmolal ICM iohexol, iopromide, and ioversol. The cellular toxicity was evaluated with the trypan blue exclusion assay, the MTT assay, and incidences of cell death. A qualitative assessment of vacuolation of the cultured NRK 52-E cells was taken as a measure of intracellular uptake of ICM. A difference in cell death incidence was observed between the iso-osmolal iodixanol and the low-osmolal iohexol, iopromide, and ioversol contrast media, with the iso-osmolal iodixanol having the least effect in each of the in vitro systems tested. The osmolality of the contrast media appeared to be the major cause for the observed in vitro toxicity.     

The effects of the iodinated X-ray contrast media iodixanol, iohexol, iopromide, and ioversol on the rat kidney epithelial cell line NRK 52-E

Nephrotoxicity, associated with the administration of iodinated X-ray contrast media (ICM), continues to be a major side effect in a significant number of vulnerable patients undergoing diagnostic X-ray imaging procedures. The molecular mechanisms underlying these adverse effects on the kidneys are unclear despite several decades of investigation. Side effects are more common after exposure to high-osmolar compared with low-osmolar ICM, suggesting that osmolality may be an important physical-chemical property related to nephrotoxicity. This investigation in cultured NRK 52-E cells, a cell line of renal origin, compares the in vitro toxicity of the iso-osmolal ICM iodixanol with the low-osmolal ICM iohexol, iopromide, and ioversol. The cellular toxicity was evaluated with the trypan blue exclusion assay, the MTT assay, and incidences of cell death. A qualitative assessment of vacuolation of the cultured NRK 52-E cells was taken as a measure of intracellular uptake of ICM. A difference in cell death incidence was observed between the iso-osmolal iodixanol and the low-osmolal iohexol, iopromide, and ioversol contrast media, with the iso-osmolal iodixanol having the least effect in each of the in vitro systems tested. The osmolality of the contrast media appeared to be the major cause for the observed in vitro toxicity.     

低浓度对比剂、低辐射剂量婴幼儿腹部CT扫描

目的探讨使用低浓度对比剂(270mgI/ml)、低辐射剂量(管电压100kV)增强CT扫描在婴幼儿腹部CT检查的可行性。方法收集因腹部实体肿瘤或外伤需接受CT增强检查的婴幼儿90例,将其分为3组:A组为平扫与实质期管电压120kV、对比剂碘克沙醇(320mgI/ml);B组为平扫与实质期管电压100kV、对比剂碘克沙醇(320mgI/ml);C组为平扫与实质期管电压100kV、对比剂碘克沙醇(270mgI/ml)。采用4分制主观评价实质期图像质量。测量实质期的皮下脂肪标准差(SD),以及肝实质、脾实质、肾皮质、肾静脉和腹主动脉SNR和CNR,记录容积CT剂量指数(CTDI_(vol))、剂量长度乘积(DLP),并计算有效剂量(ED)。对3组数据进行统计学分析。结果 3组实质期肝实质、脾实质、肾皮质、肾静脉和腹主动脉的SNR、CNR及主观评分差异均无统计学意义(P均0.05)。3组CTDI_(vol)、DLP、ED差异有统计学意义(P均0.01)。A组CTDI_(vol)(P=0.001、0.002)、DLP(P=0.013、0.004)、ED(P=0.003、0.001)与B组、C组比较差异均有统计学意义,B、C组CTDI_(vol)、DLP、ED差异无统计学意义(P均0.05)。结论采用低浓度对比剂(270mgI/ml)联合100kV管电压进行CT增强扫描,可保证婴幼儿腹部图像的CNR,并满足临床诊断要求。     

Premedication and short term complications in iohexol discography.

In 52 patients 0.5-3.0 ml of iohexol, 180 mg/ml, was injected using lateral injection technique and fluoroscopy control. A total of 146 lumbar discs using local anaesthesia was injected. Two types of premedication were used; either diazepam alone or diazepam in combination with pethidine and glycopyrronium bromide. There was no difference in the discography injection pain between the groups (X2 = 0.774, P greater than 0.05]. During discography, some patients had nausea (2%), convulsions (4%), back pain (6%) and hypotension (10%), but no allergic reactions were seen. This suggests that these immediate reactions are more related to the procedure itself than to the non-ionic ratio 3.0 iohexol contrast medium. More troublesome iatrogenic complications were seen the day after the discography in the form of severe headache (10%) probably related to liquor leakage, and increasing low back pain (81%). The latter may be caused by local haematoma or chemical irritation from iohexol. Patients with no pain during injection had a relatively slight need for analgesics (Somer's D = -0.196, P less than 0.05).     

Delayed Hypersensitivity Reaction After Infusion of Nonionic Intravenous Contrast Material for an Excretory Urogram: A Case Report and Review of the Literature

Delayed adverse reactions to ionic and nonionic intravenous contrast media have been reported previously. We report a case in which delayed hypersensitivity to iohexol, a nonionic intravenous contrast agent commonly used in excretory urography, resulted in a bi-phasic allergic response. This reaction consisted of a mild post-infusion episode of urticaria, which preceded and was clinically distinct from a moderately severe dermatological eruption. The episode of urticaria was self-limited. The dermatological reaction was treated successfully with antihistamine therapy.     

Nephrotoxicity of iso-osmolar versus low-osmolar contrast media is equal in low risk patients

BACKGROUND: Contrast media-induced nephropathy (CIN) is an increasing cause of hospital-acquired acute kidney injury and leads to a significant increase in mortality. There is uncertainty whether the use of iso-osmolar contrast media as opposed to the use of low-osmolar contrast media would be associated with a lower incidence of CIN. Therefore, we compared the nephrotoxicity of isoosmotic contrast media iodixanol with the low-osmotic contrast media iopromid in patients receiving contrast media during coronary angiography. METHODS: In this prospective double-blind study we examined 221 patients with normal renal function who received up to 1,000 ml of contrast media during coronary angiography, and compared the effect of iodixanol and iopromid on inducing contrast media nephropathy. Patients received 800 ml fluid orally before contrast media administration and 1,000 ml saline i.v. thereafter. Creatinine clearance, serum creatinine and urine-N-acetyl-beta-D-glucosaminidase (NAG) concentration was obtained 24 h before and 48 h after contrast media administration. Decrease of 20% of the creatinine clearance, increase of 25% of serum creatinine and increase of 20% of the urine concentration of NAG was defined as CIN. RESULTS: Incidence of CIN assessed by decreased creatinine clearance was 22.2% in the iopromid group and 19.7% in the iodixanol group. CIN defined by increased serum creatinine was 6.9% in the iopromid group and 8.6% in the iodixanol group. The difference between these two groups was not significant. Subgroup analysis of the diabetic patients or the patients that received high dose of contrast media revealed no significant difference in the incidence of CIN between the two contrast media. CONCLUSION: The iso-osmolar and the low-osmolar contrast media exhibited the same incidence of CIN in our study population. If fluid administration is sufficient, the selection of either iopromid or iodixanol has no impact on the risk of developing CIN in patients with normal renal function, even when they are diabetic or receive a high dose of more than 500 ml contrast media.     

Glutathione and Glycine in Acute Renal Failure

Background. Ochratoxin A (OTA) is a nephrotoxic metabolite occurring in foodstuffs. In the last decade, OTA‐induced nephropathy in man and animals have been confirmed by previous literature. The correlation between OTA and the severity of CRI and nephrotic syndrome was also researched. Therefore, this study was designed to determine whether OTA also played an important role in renal insufficiency of patients with chronic renal diseases in Taiwan. Methods. The patients in this study were divided into nonnephrotic syndrome and nephrotic syndrome groups, first, to look for the relation between urine protein and OTA. And then these patients were also divided into six groups: (I) patients with chronic glomerulonephritis; (II) patients with chronic interstitial nephritis; (III) patients with diabetes mellitus; (IV) patients with hypertension; (V) patients with other diseases; (VI) patients with unknown reasons. For all groups, laboratory evaluation of kidney such as serum creatinine, urinary creatinine, creatinine clear rate, urinary protein, and urinary analysis were carried out coupled with determination of ochratoxin A level in urine. Results. Higher levels of OTA were found in patients with nephrotic syndrome. There was a significantly positive correlation (P < 0.001) between 24‐hr OTA and 24‐hr urine protein. On the other hand, the mean excretion of OTA in DM group (group III) was found significantly higher compared to the other groups (P < 0.05). Distinct differences (P < 0.01) were found especially when DM group was compared with patients with chronic glomerulonephritis (group I; P = 0.0019), patients with chronic interstitial nephritis (group II; P = 0.0032) and patients with hypertension (group IV; P = 0.0062). Conclusion. The results could lead to the conclusion that OTA could play an important role in proteinuria of patients with chronic renal diseases in Taiwan. And OTA may play a role in diabetes patients with nephropathy. Further longitudinal study is needed to clarify the role of OTA in diabetic nephropathy.     

Risk factors of postoperative nephropathy in patients undergoing innovative CABG and intraoperative graft angiography.

INTRODUCTION: Intraoperative graft angiography is considered gold standard in quality control of innovative CABG techniques. Iodixanol, an iso-osmolar, non-ionic contrast agent has been safely applied in patients with impaired renal function. We aimed to quantify postoperative nephropathy in CABG patients undergoing intraoperative angiography and to define associated risk factors. METHODS: One hundred and thirty-five patients, aged 61 years (range: 43-83), underwent intraoperative angiography following CABG (36 robotically assisted CABG via sternotomy, 41 OPCAB and MIDCAB, 51 AHTECAB, 7 BHTECAB). In all patients iodixanol (Visipaque) was used, median amount: 150 ml (range: 20-500). Nephropathy was defined as an increase in serum creatinine concentration >or= 0.5 mg/dl compared with preoperative values. RESULTS: Nephropathy occured in 19/135 (14%) patients, and was correlated with the following variables: preoperative serum creatinine (p = 0.015, r = 0.208), age (p = 0.008, r = 0.229), postoperative peak troponin T levels (p < 0.001, r = 0.545), postoperative CK-MB peak levels (p = 0.028, r = 0.189), and presence of peripheral vascular disease (p = 0.011). No correlation was found for the contrast agent amount, diabetes mellitus, hypertension, preoperative urea level, cardiopulmonary bypass time, aortic cross clamp time, postoperative CK peak levels. Multivariate analysis showed that postoperative peak troponin T levels (p < 0.001), preoperative serum creatinine (p = 0.031), and patient age (p = 0.043) were independently associated with a postoperative increase of serum creatinine. In all 19 patients with postoperative nephropathy serum creatinine levels returned to preoperative levels. CONCLUSION: Patients with older age and elevated serum creatinine levels undergoing innovative CABG and intraoperative angiography were at increased risk of postoperative nephropathy. However, no correlation was found between the amount of contrast agent (iodixanol) applied and the nephropathy rate and none of the nephropathy cases persisted.     

Effect of low-osmolar contrast medium iopromide and iso-osmolar iodixanol on DNA fragmentation in renal tubular cell culture

Background

Intravascular administration of iodinated contrast media continues to be a common cause of hospital-acquired acute kidney injury. Accumulating evidence suggests that radiocontrast agent-induced nephrotoxicity is associated with increased oxidative stress, which leads to renal tissue damage with DNA fragmentation. We therefore tested whether an iso-osmolar contrast medium (iodixanol) causes less oxidative DNA damage to renal tubular cells than a low-osmolar contrast medium (iopromide).

Methods

HK-2 cells (human proximal renal tubular cell line) were incubated at different time points (10 min–2 h) with increasing concentrations (20–120 mg/ml iodine) of iodixanol or of iopromide. Oxidative DNA damage to renal tubular cells was measured by alkaline comet assay (single-cell gel electrophoresis).

Results

Both iso- and low-osmolar contrast agents induced time- and concentration-dependent DNA fragmentation. DNA fragmentation was maximal at 2 h with 120 mg/ml iodine for iopromide (32 ± 27 tail moments) and iodixanol (46 ± 41 tail moments); both were significantly different from the control value with 3.15 ± 1.6 tail moments (Student’s t test; p < 0.001). After 1 and 2 h and for all concentrations, iodixanol produced significantly higher DNA fragmentation than iopromide (ANOVA for 1 h p = 0.039 and 2 h p = 0.025, respectively).

Conclusion

We were able to demonstrate for the first time that an iso-osmolar contrast medium induced even greater oxidative stress and DNA damage than a low-osmolar agent in HK-2 cells. This could provide an explanation for the nephrotoxicity that also is observed with iodixanol in clinical practice.     

Evaluation of cystatin C with iohexol clearance in cardiac surgery

Background: Post‐operative renal dysfunction after cardiac surgery is not uncommon and can lead to adverse outcome. The ability to accurately monitor renal function is therefore important. Cystatin C is known to be a sensitive marker of the glomerular filtration rate (GFR), but it has not been fully evaluated in cardiac surgery. Iohexol clearance is considered a reliable reference method for the determination of GFR. The aim of this study is to, for the first time, evaluate the diagnostic accuracy of plasma cystatin C compared with iohexol clearance in cardiac surgery. Methods: Twenty‐one patients scheduled for elective coronary artery bypass grafting were prospectively enrolled in the study. Before surgery and on the second post‐operative day, an iohexol clearance was performed. Plasma cystatin C, plasma creatinine and plasma C‐reactive protein were determined before surgery and on the first, second, third and fifth post‐operative day. Estimated creatinine and cystatin C clearances were determined. Results: Post‐operative cystatin C and 1/cystatin C correlated strongly to iohexol clearance (r=?0.90 and 0.86) and so did creatinine and 1/creatinine (r=?0.83 and 0.78). Estimated creatinine clearance differed from iohexol clearance (P<0.01), whereas estimated cystatin C clearance did not differ from iohexol clearance (P=0.81). No correlation was found between C‐reactive protein and cystatin C. Conclusion: This study indicates that clearance estimations based on cystatin C are more accurate compared with estimations based on creatinine in determining GFR in cardiac surgery. Cystatin C has, in this study population, a stronger correlation to iohexol clearance than creatinine.     

The relative renal safety of iso -osmolar contrast media compared with low -osmolar contrast media in intravenous contrast-enhanced CT: a Meta-analysis

Objective To compare the nephrotoxicity of the iso ? osmolar contrast media (iodixanol) to low?osmolar contrast media (LOCM) in intravenous contrast?enhanced CT. Methods Randomized controlled trials (RCTs) of iodixanol or low?osmolar contrast media in intravenous contrast?enhanced CT were searched in the database of VIP, CBM, CNKI, Wanfang, PubMed, EMBASE, Web of Science, Cochrane Library from their start year to July 2012. Screening and information extracted were did by two researchers independently. The quality of the included documents was evaluated by the criterion of Cochrane handbook. Revman software (version 5.0) of the Cochrane collaboration was used in data analysis. Results There was no significant difference in the incidence of contrast?induced nephropathy (CIN) among 6 trials recruited 907 patients between the iodixanol group and the LOCM group [RR=0.64, 95%CI (0.31 ? 1.32), P=0.22] by using serum creatinine increased by more than 44 μmol/L (0.5 mg/dl) as the diagnostic criteria. No considerable difference was existed by using serum creatinine increased by more than 25% as the diagnostic criteria between the two groups [RR=0.79, 95%CI (0.48?1.30), P=0.35]. Subgroup analysis showed there was no obvious difference [RR=0.57, 95%CI (0.30 ? 1.10), P=0.09] between the two groups in patients with increased baseline of serum creatinine. No obvious difference were gained in normal baseline group [RR=1.28, 95%CI (0.57?2.86), P=0.55] . Conclusion Compared with low?osmolar contrast media, iodixanol is not associated with less CIN in intravenous contrast?enhanced CT.     

Contrast-induced nephropathy--prevention and risk reduction.

Contrast-induced nephropathy (CIN) is a serious, but potentially preventable adverse event associated with the use of iodinated contrast media (CM). Studies suggest that the occurrence of CIN is directly related to the number of pre-existing patient risk factors such as pre-existing renal insufficiency (RI) with or without diabetes, advanced age, congestive heart failure and dehydration. Because the risk factors for CIN are common and the consequences serious or even life-threatening, it is important for physicians to implement preventive strategies. Although the optimal strategy for preventing CIN has not been fully established, it is important to first identify patients at risk. The commonly used methods for identifying patients at risk include use of patient questionnaires, review of medical history and measurement of serum creatinine levels prior to the administration of CM. Estimation of the glomerular filtration rate (GFR) before CM administration should be encouraged. To prevent the development of CIN, patients should be well-hydrated and nephrotoxic medications should be withdrawn at least 24 h prior to CM. Use of the minimal necessary CM dose is recommended, as the nephrotoxic effect of CM is dose-dependent. Furthermore, appropriate selection of CM is important. The incidence of CIN has been shown to be lower when an iso-osmolar CM rather than a low-osmolar CM (iohexol) is used in patients with RI and diabetes. Pharmacological intervention with calcium channel blockers, dopamine and N-acetylcysteine have not consistently been shown to reduce the incidence of CIN. This article will review the risk factors for the development of CIN and discuss practical strategies for its prevention in at-risk patients.