Review: Low-osmolality contrast media is associated with less deterioration in renal function in high-risk patients
ACP J Club. 1993 Nov-Dec;119:74. doi:10.7326/ACPJC-1993-119-3-074
Barrett BJ, Carlisle EJ. Meta-analysis of the relative nephrotoxicity of high- and low-osmolality iodinated contrast media. Radiology. 1993 Jul;188:171-8
To determine if low-osmolality contrast media (LOCM) are less nephrotoxic than high-osmolality contrast media (HOCM) and to determine if the nephrotoxicity is greater for patients with renal impairment.
Studies were identified using MEDLINE (1982 to 1991), EMBASE, personal files, bibliographies of review articles and relevant papers, and contact with authors and pharmaceutical companies.
Studies were selected if they were randomized controlled trials in English comparing intravascularly administered LOCM and HOCM, if they measured serum creatinine (SCr) levels or glomerular filtrafion rates before and after receiving contrast media, or measured need for dialysis after receiving contrast media.
Data were extracted to calculate the relative effects of LOCM and HOCM for all patients and for those with preexisting renal impairment using odds ratios (ORs) for incidence of increase in SCr levels of > 44 µmol/L (0.5 mg/dL); the effect size for means of continuous variables (SCr levels, glomerular filtration rate) adjusted according to sample size and standard deviation; and pooled P values.
31 studies with 5146 patients were eligible for analyses. The pooled effect size for differences in the change in SCr levels and glomerular function was small (- 0.058 SD, 95% CI - 0.14 to 0.02) and was equivalent to mean changes in SCr that were 0.2 to 6.2 µmol/L less using LOCM compared with HOCM. From 25 studies, the pooled OR of the difference in the proportion of patients with an increase in SCr levels of > 44 µmol/L was 0.61 (CI 0.48 to 0.77), favoring LOCM. For diabetic patients with renal impairment, the pooled OR for increases in SCr levels of > 44 µmol/L was 0.54 (CI 0.3 to 0.9), and for all patients with renal impairment the pooled OR was 0.5 (CI 0.36 to 0.7), both in favor of LOCM. The pooled effect size for differences in the mean changes in renal function, however, was small (-0.06 SD, CI - 0.22 to 0.09) and the difference was not statistically significant in patients with renal impairment exposed to LOCM compared with those exposed to HOCM. 4 studies examined large changes in renal function (increases in SCr levels of > 90 µmol/L) for patients with renal impairment. The pooled OR was 0.44 (CI 0.26 to 0.73), favoring LOCM.
Low-osmolality contrast media reduces the incidence of elevations of serum creatinine levels compared with high-osmolality contrast media. The overall benefit is small; the greatest benefit occurs in those with preexisting renal impairment.
Source of funding: Kidney Foundation of Canada.
For article reprint: Dr. B.J. Barrett, Division of Nephrology, Health Sciences Centre, 300 Prince Phillip Drive, St. John's, Newfoundland A1B 3V6, Canada. FAX 709-737-6995.
Acute renal failure (ARF) resulting from iodinated radiocontrast media occurs rarely among low-risk patients without preexisting renal insufficiency or volume depletion. The probability of ARF occurring (> 25% increase in SCr levels) among high-risk patients receiving HOCM is estimated to be between 5% and 10%. Severe radiocontrast associated ARF requiring dialysis occurs much less frequently, probably in 1% to 2% of patients. LOCM, which cause less pain and fewer nonrenal adverse events, have been proposed as substitutes for HOCM to reduce the risk for radiocontrast-associated ARF. Although many clinical trials have compared the renal toxicity of HOCM and LOCM, until 1995 most had found no statistical differences in the risk for ARF, perhaps because small sample sizes provided inadequate power to detect differences. A recent randomized trial of more than 1100 patients undergoing cardiac catheterization showed a reduced risk for ARF (SCr increase by ≥ 1 mg/dL) after LOCM exclusively among the subset of patients with baseline SCr ≥ 1.5 mg/dL (1). Because of their high cost and the continued uncertainty of their protective effect on kidney function, the appropriate role of LOCM remains controversial. Therefore, the meta-analysis by Barrett and Carlisle represents a timely and important contribution.
Meta-analyses increase statistical power by pooling the results of many trials and often permit detection of clinically important differences between treatments not apparent from the results of individual trials. Overall, the analysis indicates that using LOCM reduces the risk and extent of ARF, but this effect was small. Subgroup analyses showed that persons with preexisting renal impairment derive greater benefit from LOCM, when ARF is defined as an increase in SCr levels of > 44 µmol/L.
This study, and now a subsequent trial by Rudnick and colleagues (1), confirms that LOCM are not necessary to preserve renal function among low-risk patients. Although LOCM have a greater beneficial effect among patients with renal insufficiency, an increase in SCr levels of > 44 µmol/L may not be the most relevant measure of ARF. Analyses using outcome measures, such as the need for dialysis, or studies of costs associated with moderate rises in SCr would help define the appropriate role of LOCM in patients with renal impairment.
Harold I. Feldman, MD, MSCE
University of PennsylvaniaPhiladelphia, Pennsylvania, USA