Association of Intravenous Radiocontrast With Kidney Function

Abstract

IMPORTANCERadiocontrast has long been thought of as nephrotoxic; however, a number of recent observational studies found no evidence of an association between intravenous contrast and kidney injury. Because these studies are at high risk of confounding and selection bias, alternative study designs are required to enable more robust evaluation of this association.OBJECTIVE To determine whether intravenous radiocontrast exposure is associated with clinically significant long-term kidney impairment, using a study design that permits stronger causal interpretation than existing observational research. DESIGN, SETTING, AND PARTICIPANTSThis cohort study included all emergency department patients aged 18 years or older undergoing D-dimer testing between 2013 and 2018 in the Canadian province of Alberta. A fuzzy regression discontinuity design was used, exploiting the fact that individuals just either side of the eligibility cutoff for computed tomographic pulmonary angiogram (CTPA)-typically 500 ng/mL-have markedly different probabilities of contrast exposure, but should otherwise be similar with respect to potential confounders.EXPOSURES Intravenous contrast in the form of a CTPA. MAIN OUTCOMES AND MEASURESEstimated glomerular filtration rate (eGFR) up to 6 months following the index emergency department visit.RESULTS During the study period 156 028 individuals received a D-dimer test. The mean age was 53 years, 68 206 (44%) were men and 87 822 (56%) were women, and the mean baseline eGFR level was 86 mL/min/1.73 m 2 . Patients just above and below the CTPA eligibility cutoff were similar in terms of measured confounders. There was no evidence for an association of contrast with eGFR up to 6 months later, with a mean change in eGFR of −0.4 mL/min/1.73 m 2 (95% CI, −4.9 to 4.0) associated with CTPA exposure. There was similarly no evidence for an association with need for kidney replacement therapy (risk difference [RD], 0.07%; 95% CI, −0.47% to 0.61%), mortality (RD, 0.3%; 95% CI, −2.9% to 3.2%), and acute kidney injury (RD, 4.3%; 95% CI, −2.7% to 12.9%), though the latter analysis was limited by missing data. Subgroup analyses were potentially consistent with harm among patients with diabetes (mean eGFR change −6.4 mL/min/1.73 m 2 ; 95% CI, −15.4 to 0.2), but not among those with other reported risk factors for contrast-induced nephropathy; these analyses, however, were relatively underpowered.CONCLUSIONS AND RELEVANCE Using a cohort study design and analysis that permits stronger causal interpretation than existing observational research, we found no evidence for a harmful effect on kidney function of intravenous contrast administered for CTPA in an emergency setting.

Invasive Versus Medical Management in Patients With Chronic Kidney Disease and Non–ST‐Segment–Elevation Myocardial Infarction

“…This might encourage physicians to subject patients more often to invasive management, following a discussion on the risk related to the procedure. Similar to these findings, Goulden et al 29 showed that contrast was not associated with increased risk of AKI or renal replacement therapy at 6 months using a regression discontinuity analysis in a quasiexperimental cohort study of 156 028 patients who underwent a computed tomography pulmonary embolism protocol. Alternatively, increased use of iso‐osmotic or low‐osmotic contrast in such patients may reduce the risk of AKI.…”

Association of Prenatal Care Services, Maternal Morbidity, and Perinatal Mortality With the Advanced Maternal Age Cutoff of 35 Years

“…Although many RD designs can be used as a form of instrumental variable analysis, in which the threshold is used as an instrument in a "fuzzy RD" framework, we did not take this additional step in this analysis. 26,28 This is because the AMA cutoff can affect perinatal and maternal outcomes through multiple channels, some of which we were able to measure with our data and some we could not. Thus, an instrumental variable analysis would not necessarily meet the exclusion restriction for instrumental variable analysis, and estimates could be biased.…”

“…Regression discontinuity overcomes the issue of selection bias in comparing individuals with and without an intervention by exploiting an arbitrary cutoff in clinical decision-making rules or program eligibility, providing transparent visual evidence of changes in the outcome at the cutoff. [26][27][28][29] The RD method relies on the assumption that individuals within a narrow bandwidth around the cutoff have similar baseline characteristics other than the likelihood of receiving the We used local linear regression, with a binary indicator for age 35 years or older on the expected date of delivery as the main independent variable. Regressions controlled for the total number of days between the individual's 35th birthday and the expected date of delivery (the running variable), prepregnancy characteristics (ie, pregestational diabetes, chronic hypertension, obesity, and multiple gestation), zip code characteristics (percent Hispanic individuals, percent White individuals, median household income, and urbanicity), and county of residence characteristics (any hospital with a neonatal intensive care unit and OBGYNs per 10 000 deliveries), with fixed effects for state of residence, year, and month of delivery to improve precision.…”

“…Regression discontinuity overcomes the issue of selection bias in comparing individuals with and without an intervention by exploiting an arbitrary cutoff in clinical decision-making rules or program eligibility, providing transparent visual evidence of changes in the outcome at the cutoff. 26 , 27 , 28 , 29 The RD method relies on the assumption that individuals within a narrow bandwidth around the cutoff have similar baseline characteristics other than the likelihood of receiving the intervention. Although the risk of adverse outcomes increases with maternal age, individuals 4 months older or younger than 35 years should not have different underlying risks.…”

Effect of Treatment in a Specialized Pediatric Hemato-Oncology Setting on 5-Year Survival in Acute Lymphoblastic Leukemia: A Quasi-Experimental Study

“…The RD design is an increasingly used quasi-experimental design in healthcare and elsewhere to investigate the causal effects of interventions [13][14][15]. It has been described as the next-best evaluation method after a randomized controlled trial (RCT) [14], and its potential in healthcare to provide evidence on treatment effects is illustrated in several recent publications [20][21][22][23][24]. The RD design is attractive as it allows for causal interpretation of estimated effects of interventions or exposures using real-world observational data.…”