Association of Intravenous Radiocontrast With Kidney Function: A Regression Discontinuity Analysis

Abstract

Importance: Radiocontrast 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 participants: This 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 measures: Estimated 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 m2. 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 m2 (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 m2; 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.

Figure 1.. Association Between D-Dimer and Primary Exposure and Potential Confounders

A, Primary exposure. B, C, and D, Potential confounders. The blue circles represent the mean value for individual patients and the dotted lines indicate the D-dimer cutoff. CTPA indicates computed tomographic pulmonary angiogram; eGFR, estimated glomerular filtration rate.

Figure 2.. Association Between D-Dimer and Long-term eGFR

A, Using a local linear approach. B, Using a global polynomial approach. The blue circles represent the mean value for individual patients, and the dotted lines indicate the D-dimer cutoff and the shaded area shows the local linear regression bandwidth. eGFR indicates estimated glomerular filtration rate.