The potential role of statins in contrast nephropathy

BACKGROUND: Administration of contrast agents may result in an acute reduction in renal function and occasionally end-stage renal disease. Risk factors for contrast-induced nephropathy (CN) are preexisting renal dysfunction, diabetes and reduced effective arterial volume. Hydration and use of nonionic contrast agents have been reported to ameliorate CN. Reactive oxygen species may have a role in the pathogenesis of CN. Statins decrease free oxygen radicals in animals. We retrospectively tested the hypothesis that administering statins prior to cardiac catheterization decreases the incidence of CN. METHODS: A total of 1,002 patients were studied. Patients with a stable baseline serum creatinine (SCr) > or = 1.5 mg/dl who had cardiac catheterization between July 1997 and June 2002, were included in the study. None of the patients were taking statins before admission. 250 patients were started on a statin before the procedure and 752 patients were not. The SCr was followed for 7 days after the procedure looking for an acute decrement in renal function, dialysis requirement and survival. RESULTS: The baseline characteristics, SCr, GFR, amount of intravenous fluids and contrast were similar in both groups. The post cath SCr (2.26 vs 3.1 mg/dl, p = 0.001) was significantly better in the statin group. Length of stay (2.72 vs 3.32 days, p = 0.01) and number of patients with acute renal failure (43 (17.2%) vs 168 (22.3%) patients, p = 0.028) were significantly lower in the statin group. Dialysis requirement within 7 days and 28-day survival were similar in both groups. CONCLUSION: Prophylactic administration of statins along with hydration may be associated with less CN induced by a nonionic, low-osmolality contrast.     

Acute renal haemodynamic effects of radiocontrast media in patients undergoing left ventricular and coronary angiography.

BACKGROUND: Tubular toxicity and renal ischaemia have been implicated in the pathogenesis of radiocontrast media induced nephropathy (CIN), but their respective role remains unclear. Aims. In order to evaluate changes in renal blood flow in response to intra-arterial contrast media administration, we aimed to continuously measure renal arterial perfusion by means of renal blood flow velocity (RBFV) during left ventricular and coronary angiography and subsequent coronary intervention in patients with chronic kidney disease (CKD). Patients and METHODS: Ten patients (7 males, 63.4 +/- 11.7 years) with serum creatinine (SCr) >1.5 mg/dl participated in the study. The first five patients received low-osmolar iopromide and the others iso-osmolar iodixanol contrast medium. RBFV was measured using a 0.014-inch Doppler guide wire, which was inserted through a separate contralateral femoral sheath via a 5 F Cobra diagnostic catheter into the renal artery. Data were recorded at 500 Hz to allow beat-to-beat analysis of RBFV and pressure. All patients were pre-treated with acetylcysteine and hydration. RESULTS: Immediately after left ventricular angiography no significant changes in RBFV were detected. Over time, however, following repeated administration of the additional contrast medium into the coronary arteries, RBFV decreased significantly from baseline until the end of the investigation, 28.4 (19.1/42.7) to 22.9 (16.9/30.6) cm/s (median and quartiles; P = 0.005), in the absence of significant changes in systemic arterial blood pressure. In individual patients the reduction in RBVF varied from 3.7% to 39.5%. On average the decline in RBFV was more pronounced in patients receiving iopromide (from 41.6 cm/s to 29.3 cm/s) than in those receiving iodixanol (from 19.3 to 17.8 cm/s; P = 0.008 for the difference of relative decline). However, in the iopromide treated patients, coronary intervention was more frequently performed (5/5 versus 2/5) and the median duration of the procedure tended to be longer [85 (32-150) min versus 38 (27-110) min; P > 0.2]. CONCLUSIONS: The administration of non-ionic low-osmolal contrast media has no immediate effect on renal perfusion in patients with CKD. However, during the course of coronary angiography a gradual decline in renal blood flow may occur, the extent of which varies, presumably depending on individual pre-disposition as well as on the amount of the contrast medium.     

尿肾损伤分子-1检测对伽玛刀治疗过程中肿瘤患者发生急性肾损伤的早期诊断

目的 近年来接受立体定向伽玛射线治疗系统（伽玛刀）治疗的肿瘤患者日益增多,我们观察到部分患者在治疗过程中并发急性肾损伤（AKI）,而肿瘤患者并发AKI后病死率明显增加,因此如何早期诊断和早期干预是防治和逆转疾病进展的关键。本研究旨在观察伽玛刀治疗过程中发生AK1的肿瘤患者尿肾损伤分子-1（KIM-1）表达水平的变化及其对AKI的早期诊断价值。方法：收集我院2007年5月-2007年11月期间于伽玛刀中心入院接受体部伽玛刀治疗的100例患者的详细资料,以伽玛刀治疗过程中血清肌酐上升超过0．3mg／dl或较基础值上升〉50％为AKI的诊断标准。ELISA方法检测伽玛刀治疗过程中（造影12h、24h、48h、伽玛刀治疗7次、伽玛刀治疗结束）肿瘤患者尿KIM-1表达水平的变化。结果：所有肿瘤患者中,25例为AKI组,75例为非AKI组。在造影12h、24h、48h和伽玛刀治疗7次各时间点,AKI组尿KIM-1水平均显著高于无AKI组（P值均〈0．05）。在造影48h和治疗结束时。AKI组血肌酐水平显著高于无AKI组（P〈0．05）,而其他时间点差异无统计学意义（P〉0．05）。经尿肌酐校正后,在造影12h、24h、48h,AKI组患者尿KIM-1／尿肌酐表达水平显著高于非AKI组（P值均〈0．05）,而其他时间点差异无统计学意义（P〉0．05）。以造影12h尿KIM-1／尿肌酐表达水平诊断AKI的灵敏度和特异度绘制ROC曲线,其AUC为0．709（95％（21为0．585-0．832,P〈0．05）,与完全随机情况下获得的AUC=0．5的差异有统计学意义（P〈0．05）。结论：肿瘤患者在伽玛刀治疗过程中,造影后12h监测尿KIM-1表达水平可以较血肌酐更早期预测急性肾损伤的发生,及时检测有利于早期干预和治疗。     

A randomized controlled trial of N-acetylcysteine to prevent contrast nephropathy in cardiac angiography

BACKGROUND: Contrast nephropathy (CN) is a common cause of renal dysfunction after cardiac angiography. Recently, N-acetylcysteine (NAC) has been found to reduce the risk of CN after CT imaging with contrast enhancement. The purpose of the current study was to evaluate the efficacy of NAC for the prevention of CN in the setting of cardiac angiography. METHODS: Eligible patients were those undergoing cardiac angiography with serum creatinine>1.7 mg/dL. Patients were randomized to one of two groups: Group 1, IV hydration and NAC, 1200 mg one hour before angiography, and a second dose 3 hours after; Group 2, IV hydration and placebo. CN was defined as an increase of 0.5 mg/dL in serum creatinine. RESULTS: Seventy-nine patients completed the study. There were no significant differences between the groups in baseline characteristics, duration of angiography, mean volume of dye infused or mean IV hydration. Contrast nephropathy developed in 24.0% of subjects, 26.3% NAC, and 22.0% placebo (P = NS). Among subjects with diabetes mellitus, there was no significant difference in the rate of CN between the groups (42.1% NAC, 27.8% placebo; P = 0.09). The independent predictors of CN risk were diabetes mellitus and preexisting chronic renal insufficiency. CONCLUSIONS: NAC was not effective for the prevention of CN after cardiac angiography.     

What is the best hydration regimen to prevent contrast media-induced nephrotoxicity?

BACKGROUND: Hydration is a commonly used method to prevent the decline in GFR after contrast media (CM) application. So far, there have been no controlled, randomized trials investigating the most effective route of fluid administration. METHODS: Thirty-nine patients with normal renal function (65 +/- 9 years, serum creatinine 0.9 +/- 0.2 mg/dl, GFR = 110 +/- 31 ml/min/1.73 m2) receiving at least 80 ml of low-osmolality CM during an angiographic procedure were randomized to one of the following hydration regimens: Group 1: volume expansion with 300 ml saline during CM administration (n = 20, serum creatinine 0.8 +/- 0.1 mg/dl, GFR 119 +/- 27 ml/min/1.73 m2); Group 2: intravenous administration of at least 2,000 ml saline within 12 h before and after CM application (n = 19, serum creatinine 0.9 +/- 0.2 mg/dl, GFR 101 +/- 32 ml/min/1.73 m2). GFR was measured by CM clearance (Renalyzer) at baseline and 48 hours after CM administration. The primary end point was the mean change in the GFR after 48 hours, the secondary one was the incidence of CM-induced nephropathy (CMIN), defined as a decrease in GFR of more than 50% from the baseline GFR within 48 hours. RESULTS: Patients of group 1 showed a significantly (p < 0.05) higher decline in GFR (delta GFR 34.6 +/- 25.7 ml/min/1.73 m2) compared to patients receiving the intravenous prehydration regimen (delta GFR 18.3 +/- 25.0 ml/min/1.73 m2). The incidence of CMIN was lower in prehydrated patients (5.3%) compared to the other group (15%). CONCLUSION: In patients with normal renal function, intravenous prehydration seems to be a very effective and feasible method to prevent the decline in GFR after contrast media exposure. Volume expansion given only during the CM exposure appears not to be sufficient enough to prevent renal damage.     

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.     

经导管动脉栓塞术中使用对比剂对肾功能的影响

目的探讨经导管动脉栓塞术(TAE)术中使用对比剂对外伤患者肾功能的影响。方法回顾性分析因腹部或盆腔急性外伤而接受TAE的80例患者,比较其术前及术后血清肌酐水平。结果术前血清肌酐为(1.02±0.24)mg/dl,术后为(0.94±0.26)mg/dl,略低于术前(P=0.01)。肾衰竭高危患者TAE后血清肌酐总体水平无明显增高。术后5例(5/80,6.25%)发生对比剂肾病,对比剂肾病发生率的95%可信区间为2%～11%;血清肌酐水平均于术后5天内恢复至基线水平。结论外伤患者TAE后可能发生对比剂肾病,但多为一过性的,TAE中使用对比剂是较为安全的。     

A randomized trial of saline hydration to prevent contrast nephropathy in chronic renal failure patients.

BACKGROUND: Contrast nephropathy (CN) is a common cause of renal dysfunction that may be prevented by saline hydration and by drugs such as theophylline or furosemide. Whether oral saline hydration is as efficient as intravenous saline hydration is unknown. The preventive efficacy of theophylline and furosemide for CN remains controversial. The purpose of the current study was to evaluate the efficacy of oral saline hydration and of intravenous saline hydration plus theophylline or furosemide for the prevention of CN. METHODS: We prospectively studied 312 patients with chronic renal failure (serum creatinine 201+/-81 micromol/l, Cockcroft clearance 37+/-12 ml/min/1.73 m(2)), who were undergoing various radiological procedures with a non-ionic, low osmolality contrast agent. Patients were randomly assigned to four arms. In arm A, patients received 1 g/10 kg of body weight/day of sodium chloride per os for 2 days before the procedure. In arm B, patients received 0.9% saline intravenously at a rate of 15 ml/kg for 6 h before the procedure. In arm C, patients received the same saline hydration as in arm B plus 5 mg/kg theophylline per os in one dose 1 h before the procedure. In arm D, patients received the same saline hydration as in arm B plus 3 mg/kg of furosemide intravenously just after the procedure. RESULTS: Patients were well-matched with no significant differences at baseline in any measured parameters. Acute renal failure, defined as an increase in serum creatinine of 44 micromol/l (0.5 mg/dl), occurred in 27 out of 312 patients (8.7%). There was no significant difference between the rate of renal failure in the different arms of the study: five out of 76 (6.6%) in arm A, four out of 77 (5.2%) in arm B, six out of 80 (7.5%) in arm C and 12 out of 79 (15.2%) in arm D. No patient had fluid overload or a significant increase in blood pressure in the 2 days following the radiological procedure. The independent predictors of CN were diabetes mellitus, high baseline serum creatinine and high systolic blood pressure. CONCLUSIONS: Oral saline hydration was as efficient as intravenous saline hydration for the prevention of CN in patients with stage 3 renal diseases. Furosemide and theophylline were not protective.     

Analysis of factors affecting the course of renal disease progression in patients with established renal insufficiency

All renal diseases ultimately progress to end-stage renal disease after renal dysfunction develops except for acute renal failure or rapidly progressive glomerulonephritis. However, renal function can be preserved for long periods in patients with mild renal insufficiency. We examined the factors affecting the progression of renal disease in patients with established renal insufficiency. We enrolled 38 patients with renal insufficiency diagnosed at the first visit and who were followed up for at least 3 years. We retrospectively recorded all information relating to serum creatinine and blood pressure levels during the follow-up periods. The patients were categorized as group A(n = 11), long-term renal survivors(at least 8 years), group B(n = 22), short-term renal survivors(3 to 8 years) and others(n = 5). Basal renal diseases were variable, and included IgA nephropathy, membranous nephropathy, focal segmental glomerulosclerosis, hypertensive glomerulosclerosis, tubulo-interstitial disease and lupus nephritis. Except for the degree of urinary occult blood, no other clinical data obtained at the first visit differed between groups A and B. Overall blood pressure levels throughout the entire clinical course also did not differ between the two groups. However, mean blood pressure levels before serum creatinine had reached the level of 2.0 mg/dl were significantly lower in group A compared with group B (96 +/- 7.8 vs. 103 +/- 6.3 mmHg, p < 0.05). We considered that the serum creatinine level of the so-called "point of no return" might be 2.0 mg/dl. In conclusion, blood pressure should be strictly controlled before serum creatinine levels reach 2.0 mg/dl.     

Exacerbation of radiocontrast nephrotoxicity by endothelin receptor antagonism

BACKGROUND: Endothelin is a potent vasoconstrictor that has been implicated in the pathogenesis of radiocontrast nephrotoxicity. Endothelin antagonists may reduce the renal hemodynamic abnormalities following radiocontrast administration. METHODS: One hundred fifty-eight patients with chronic renal insufficiency [mean serum creatinine +/- SD = 2.7 +/- 1.0 mg/dL (242. 3 to +/- 92.8 micromol/L)] and undergoing cardiac angiography were randomized to receive either a mixed endothelin A and B receptor antagonist, SB 290670, or placebo. All patients received intravenous hydration with 0.45% saline before and after radiocontrast administration. Serum creatinine concentrations were measured at baseline, 24 hours, 48 hours, and 3 to 5 days after radiocontrast administration. The primary end point was the mean change in serum creatinine concentration from baseline at 48 hours; the secondary end point was the incidence of radiocontrast nephrotoxicity, defined as an increase in serum creatinine of > or =0.5 mg/dL (44 micromol/L) or > or = 25% from baseline within 48 hours of radiocontrast administration. RESULTS: The mean increase in serum creatinine 48 hours after angiography was higher in the SB 209670 group [0.7 +/- 0. 7 mg/dL (63.5 +/- 58.6 micromol/L)] than in the placebo group [0.4 +/- 0.6 mg/dL (33.6 +/- 55.1 micromol/L), P = 0.002]. The incidence of radiocontrast nephrotoxicity was also higher in the SB 209670 group (56%) compared with placebo (29%, P = 0.002). This negative effect of SB 209670 was apparent in both diabetic and nondiabetic patients. Adverse effects, especially hypotension or decreased blood pressure, were more common in the SB 209670 group. CONCLUSIONS: In patients with chronic renal insufficiency who were undergoing cardiac angiography, endothelin receptor antagonism with SB 209670 and intravenous hydration exacerbate radiocontrast nephrotoxicity compared with hydration alone.     

Safety of gadolinium contrast angiography in patients with chronic renal insufficiency

OBJECTIVE: To prevent iodinated contrast medium-induced nephrotoxicity, gadolinium has been used increasingly for magnetic resonance angiography (MRA) or conventional digital subtraction angiography (DSA) to visualize arterial anatomy in patients undergoing vascular surgery who are considered at high risk because of chronic renal insufficiency. We assessed the safety of gadolinium-based contrast medium as a substitute for iodinated contrast medium-enhanced examinations. We determined the incidence of gadolinium-induced nephrotoxicity in a clinical setting and searched for contributing risk factors.Patients and methods In a single-center retrospective study from December 1999 to January 2001, 218 inpatients underwent MRA and 42 inpatients underwent DSA, with gadolinium as the sole contrast agent. Patient comorbid conditions, indications for vascular imaging, contrast dose, urine output, baseline and post-procedure serum creatinine concentration (SCr), and outcome were recorded for all patients in whom gadolinium-induced renal failure developed. RESULTS: Of 260 patients who received gadolinium-based contrast agents, at a dose of 0.25 mmol/kg or more, 195 patients (75%) had pre-test baseline chronic renal insufficiency. In 7 of 195 patients (3.5%) acute renal failure developed after gadolinium-based contrast medium administration, for MRA (n = 153) in 3 patients (1.9%) and DSA (n = 42) in 4 patients (9.5%). Average baseline SCr in the 195 patients with chronic renal insufficiency was 38.2 +/- 1.6 mL/min/1.73 m(2), and in the 7 patients in whom acute renal failure developed, baseline SCr was 32.5 +/- 7.8 mL/min/1.73 m(2) (P =.33). Respective intravenous and intra-arterial gadolinium doses in these 7 patients ranged from 0.31 to 0.41 mmol/kg for MRA and 0.27 to 0.42 mmol/kg for DSA. Acute renal failure did not develop in any of 65 patients with normal baseline SCr. CONCLUSION: Despite reports of negligible nephrotoxicity, rarely gadolinium-based contrast agents can cause acute renal failure in patients with underlying chronic renal insufficiency. Estimation of creatinine clearance alone does not enable prediction of which patients are likely to have acute renal failure. Patients at high-risk should be identified, and prophylactic measures should be taken to reduce the risk for nephrotoxicity.     

Gadolinium as an alternative contrast agent for diagnostic and interventional angiographic procedures in patients with impaired renal function.

BACKGROUND: The study was designed to investigate the safety and feasibility of gadopentetate dimeglumine, a gadolinium-based contrast medium, as an alternative angiographic contrast agent in patients with impaired renal function and high risk for iodinated contrast-induced nephropathy. METHODS: Gadopentetate dimeglumine was used as the radiographic contrast agent in 32 diagnostic or interventional angiographic procedures in 29 patients (59% diabetics) with severe renal insufficiency (average serum creatinine of 3.6+/-1.4 mg/dl). The average dose of gadopentetate dimeglumine was 0.34+/-0.06 mmol/kg body weight. Gadopentetate dimeglumine was used either alone (n=20) or in conjunction with carbon dioxide (n=12). RESULTS: Thirty-two angiographic procedures (24 diagnostic angiographies and 8 interventional procedures) were performed in 29 patients. For diagnostic purposes, eleven selective renal arteriographies, six angiographies of the iliac arteries and lower extremities, and seven venous angiographies of the upper extremity and central veins were performed. Interventional procedures consisted of two percutaneous transluminal renal angioplasties with stenting, four percutaneous peripheral vascular interventions, and two balloon angioplasties of a dialysis fistula. None of the patients, except one, had evidence of post-procedure contrast material-induced renal failure (increase in serum creatinine >0.5 mg/dl within 72 h) or other complications. This patient had a clinically important increase in serum creatinine level after percutaneous transluminal renal angioplasty and stenting, probably due to cholesterol embolism. Gadopentetate dimeglumine had sufficient radiographic density to allow adequate diagnostic visualization with digital subtraction equipment in all cases. CONCLUSIONS: Gadopentetate dimeglumine is an alternative and safe radiographic contrast agent for angiography and interventional procedures in patients with severe pre-existing renal impairment. In this population with high risk for contrast-induced acute renal failure, it is obviously less nephrotoxic than iodinated contrast media.     

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.     

Renal toxicity of interleukin-2 administration in patients with metastatic renal cell cancer: effect of pre-therapy nephrectomy

Systemic administration of interleukin-2 and lymphokine-activated killer cells is a new approach to the immunotherapy of advanced cancer. Metastatic renal cell cancer is one of the histological types of tumors particularly susceptible to this treatment approach although renal toxicity often is a dose-limiting side effect. We compared the renal functional changes observed during interleukin-2 therapy in 52 consecutive patients with advanced renal cancer to that of 83 consecutive patients with metastatic nonrenal cancer. Of the 52 patients with renal cancer 41 had recently undergone nephrectomy. The over-all peak serum creatinine values and the percentage increase of serum creatinine over baseline for all patients studied were significantly higher in cycle 2 of interleukin-2 therapy than in cycle 1: 3.8 +/- 0.2 versus 2.6 +/- 0.1 mg. per dl. and 241.7 +/- 16.5 versus 140.3 +/- 11.0 per cent, respectively. In patients with pre-therapy serum creatinine values of 0.4 to 0.9 mg. per dl. there were no significant differences in the mean peak serum creatinine nor in the percentage increase over baseline between renal and nonrenal cancer patients during cycle 1. In cycle 2 of therapy these values were higher in the renal cancer group (3.6 +/- 0.8 versus 2.4 +/- 0.2 mg. per dl. and 310.4 +/- 103.5 versus 214 +/- 30.4 per cent, respectively) but they did not reach statistical significance (P2 = 0.08 and 0.25, respectively). Renal and nonrenal cancer patients with pre-therapy serum creatinine levels of 1.0 to 1.4 mg. per dl. achieved similar high values in cycle 2 of interleukin-2 therapy (3.9 +/- 0.3 versus 3.9 +/- 0.4 mg. per dl. and 222.7 +/- 23.2 versus 248.7 +/- 33.5 per cent, respectively), although the initial increase (cycle 1) was higher in the renal cancer patients (3.3 +/- 0.3 versus 2.4 +/- 0.2 mg. per dl. and 172.3 +/- 25.9 versus 116.1 +/- 18.0 per cent, respectively). Baseline serum creatinine greater than or equal to 1.5 mg. per dl. was associated with an over-all higher peak serum creatinine and higher percentage increase of serum creatinine over baseline than that below 1.5 mg. per dl. baseline: 4.4 mg.per dl. and 171.1 +/- 36.3 per cent in cycle 1 and 6.5 +/- 0.7 mg. per dl. and 296.1 +/- 44.0 per cent in cycle 2, respectively (p less than 0.01). There was no association between peak serum creatinine and interval from nephrectomy to interleukin-2 therapy.(ABSTRACT TRUNCATED AT 400 WORDS)     

Prevention of radiocontrast-media-induced nephropathy in patients with pre-existing renal insufficiency by hydration in combination with the adenosine antagonist theophylline.

BACKGROUND: Radiographic contrast media (CM) application causes a decline in renal function, especially in patients with pre-existing renal dysfunction. In addition to hydration, several vasodilating substances have been evaluated for their ability to prevent renal damage after CM application. In a prospective, double-blind, placebo-controlled study we investigated the effect of the oral administration of theophylline, an adenosine receptor antagonist, on changes in renal haemodynamics and tubular injury induced by CM in well-hydrated patients with mild-to-moderate renal insufficiency. METHODS: We studied 80 patients with pre-existing chronic renal insufficiency (creatinine > 1.5 mg/dl) who received more than 100 ml iopromide. Hydration (either oral or intravenous) started at least 24 h before and lasted until 24 h after CM application. In addition, patients were randomly assigned to receive either theophylline (810 mg daily) or placebo. Serum creatinine and creatinine clearance were measured before and for 3 days after CM application. Urine was collected to measure N-acetyl-beta-glucosaminidase (NAG) enzymuria for the same period. Sixty-four patients completed the entire study protocol (theophylline, n = 35 and placebo, n = 29). RESULTS: During the study period serum creatinine concentration and creatinine clearance did not change significantly in either group. Acute renal failure (increase of serum creatinine of at least 0.5 mg/dl) could be observed in two patients from the theophylline group (5.7%) and one from the placebo group (3.4%). The increase in NAG excretion reached statistical significance (P < 0.05) in the placebo group on days 2 and 3 after CM application. CONCLUSIONS: Our results indicate a role for adenosine in CM-induced tubulotoxicity. However, the glomerular filtration rate is preserved by hydration alone in these patients. The application of theophylline did not bring an additional benefit. The use of adenosine antagonists may be beneficial in patients where sufficient hydration may be impossible or in patients with a concomitant decrease in renal blood flow (e.g. congestive heart failure).     

Effects of N-acetylcysteine on renal hemodynamics in contrast media-induced nephropathy

Background: N-acetylcysteine (NAC) has been proposed to prevent radiocontrast nephropathy in high-risk patients. Methods: The effect of single-dose and prolonged administration of NAC before application of either the ionic, high-osmolar radiocontrast agent diatrizoate sodium (DTZ) or the nonionic, low-osmolar radiocontrast agent iohexol (IOH) in a rat model combining uninephrectomy, salt depletion, and administration of indomethacin was explored. Arterial blood pressure and total, cortical, and medullary blood flow were continuously recorded in anesthetized Sprague-Dawley rats. Results: NAC had no effect on renal hemodynamics in control rats. Both DTZ and IOH induced biphasic changes in renal blood flow and cortical renal blood flux and persistently reduced medullary blood flux. Neither single-dose nor prolonged administration of NAC prevented the hemodynamic changes following administration of DTZ or IOH, respectively. Acute prophylactic administration of NAC prevented increased urinary ET excretion after injection of IOH and, to a smaller degree, of DTZ. Both an ionic, high-osmolar (DTZ) and a nonionic, low-osmolar (IOH) radiocontrast agent induce marked changes in renal hemodynamics in salt-depleted rats treated with indomethacin. Conclusions: Renal perfusion is not affected by NAC application in a model of experimental contrast nephropathy in rats. Other effects of NAC might thus account for the presumed renoprotective properties.     

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.     

The role of theophylline in contrast-induced nephropathy: a case-control study.

BACKGROUND: Various strategies for the prevention of contrast-induced nephropathy (CN) have been studied, with conflicting results. Adenosine may play an important role in the pathogenesis of CN. This study prospectively assessed the role of oral theophylline in the prevention of CN. METHODS: We randomized into two groups 70 patients with diabetes mellitus who were undergoing coronary angiography (CAG) with high-osmolar contrast media. Group I (n=35) underwent routine CAG, and group II (n=35) received oral theophylline 200 mg b.d. 24 h before and for 48 h after CAG. Serum Na(+), K(+), blood urea nitrogen (BUN), creatinine, osmolality, glomerular filtration rate (GFR) and urinalysis were performed before and after CAG. The (99m)Tc-DTPA-clearance method was used to assess GFR. RESULTS: Following angiography, patients in the control group showed a significant rise in serum creatinine (1.19+/-0.23 vs 1.44+/-0.32 mg/dl, P=0.003) and BUN (13.95+/-2.61 vs 17.55+/-3.9 mg/dl, P=0.01) along with a fall in GFR (85.4+/-14.7 vs 66.85+/-14.8 ml/min, P=0.008). The mean percentage fall in GFR was 35.8%. There was no significant change in serum creatinine (1.16+/-0.18 vs 1.24+/-0.21 mg/dl), BUN (12.8+/-3.36 vs 14.8+/-2.5 mg/dl) and GFR (86.8+/-15.8 vs 80.3+/-16.0 ml/min) in those receiving theophylline. No patient in the theophylline group had a >25% rise in serum creatinine, compared with 7/35 in the control group (P=0.017). In the control group, 11/35 (31%) developed CN, as demonstrated by a >/=25% fall in GFR, while only one patient in the theophylline group had a fall in GFR (P=0.004). None of the pre-angiographic variables could predict the development of CN. CONCLUSIONS: Following the use of high-osmolar contrast media for routine CAG, CN may develop in 31% of diabetic patients. Patients who received prophylactic oral theophylline had a significantly lower risk of CN than those who did not.     

Effect of timing of cyclosporine administration on recovery from renal ischemia in rats

The effect of timing of cyclosporine administration on functional recovery from renal ischemia was studied in Sprague-Dawley rats. Animals were given cyclosporine and subjected to renal ischemia by temporarily occluding both the renal artery and vein. Our data demonstrate no significant difference in serum creatinine among rats subjected to renal ischemia, cyclosporine, or cyclosporine-vehicle cremophor EL administration, or the control group. On the other hand, renal ischemia in combination with cyclosporine resulted in rapid and marked deterioration in renal function with serum creatinine peaking on Day 2. The most significant rise was in rats that received cyclosporine 4 hr prior to induction of renal ischemia (4.7 +/- 0.5 mg/dl), followed by those that received cyclosporine 4 and 24 hr postischemia (2.8 +/- 0.5 and 3.2 +/- 0.7 mg/dl, respectively). Cyclosporine administration 24 hr prior to renal ischemia resulted in the least elevation of the serum creatinine (2.1 +/- 0.5 mg/dl) and the earliest return to the baseline value. Our data suggest that the timing of cyclosporine administration in rats subjected to renal ischemia influences the extent of renal injury and the subsequent recovery of renal function.