Post Author: Dr. Earl C. Williams, Jr.
Citation: Goulden R, Rowe BH, Abrahamowicz M, Strumpf E, Tamblyn R. Association of Intravenous Radiocontrast With Kidney Function: A Regression Discontinuity Analysis. JAMA Intern Med. 2021 Jun 1;181(6):767-774. doi: 10.1001/jamainternmed.2021.0916. PMID: 33818606; PMCID: PMC8022267.
Background
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.
Study Question:
The primary aim of this study was 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:
Ok. Let’s make this quick and painless.
Study Design:
- Cohort study
- 2013-2018
- Canadian province of Alberta
- Fuzzy Regression Discontinuity Design
Inclusion Criterion:
- Age ≥ 18 with positive D-dimer (most cases >500mg, others >460/470mg)
Exclusion Criterion:
- Negative D-dimer testing
- Missing baseline eGFR (within 2 hrs of D-dimer)
- Dialysis/Renal Transplant within 6 months
Methods:
- D-dimer cutoff 500 most hospitals
- Some hospitals used 460/470
- Exclude if value = cutoff
- Subgroup analysis via Altman x Bland
- eGFR measure between 7 days and 6 months
- Analysis limited to completed cases
Outcomes:
- 156,028 meet criterion
- 44% women, 56% men
- eGFR baseline 86mL/min
- Mean age 53yrs
- 23% discontinuity in CTPA at D-dimer
- No discontinuity for potential confounders
Results:
- Primary Outcome
- No evidence for an association of contrast with elevated eGFR up to 6 months later, with a mean change in eGFR of −0.4
- Secondary Outcome
- No evidence for an association with need for kidney replacement therapy or mortality
- Subgroup analyses
- Potentially consistent with harm among patients with diabetes (mean eGFR change −6.4) No harm among those with other reported risk factors for contrast-induced nephropathy. Portion of study underpowered
Limitations:
Generalizability of Results
Generalizability of Results is a general limitation of RDD. Treatment effect is estimated for values close to cutoff. Unfortunately, this means that treatment effect many not apply for values further away from cutoff. Additionally, treatment effect is further restricted to those at cutoff who are compliers. Problems present themselves when considering that patients who are perceived to be at higher risk of kidney injury are less likely to have their CTPE determine by dimer result presenting a potential bias.
Violation of Exclusion Restriction
Violation of Exclusion Restriction presents itself in the form of possible pre-treatment exposures that could confound results. Exposures other than IV contrast are affected by crossing the cutoff. Its likely that patient with higher risks of kidney injury received prophylactic pre-hydration to mitigate risk of contract induced nephropathy. Unfortunately, experimenters weren’t able to measure this directly due to the fact that treatment plan weren’t recorded and analysis. It’s difficult to assess if mitigation strategies would mask harm from contrast for this experiment making it a potential confounder.
Discussion:
Using a cohort study design and analysis that permits stronger causal interpretation than existing observational research, there was no evidence found to suggest that IV contrast compromises long term kidney function.
Take Away:
Contrast is commonly seen as nephrotoxic secondary to increased creatinine values after its use in CT scanning. These concerns, in addition to renal risk factors, regularly deter medical professionals from using this modality to assess symptom etiology via CT when contrast is necessitated. When using the standard tool to assess need for renal replacement therapy (eGFR), it becomes obvious that long term detriment to kidney function isn’t necessarily supported by creatinine elevations. This dichotomy puts the emergency medical professional in a tough position. On the one hand, short term creatinine elevation as a signal of acute kidney injury is well documented, understood, and avoided. eGFR isn’t a regular assessment tool used in the ED to obtain CT scans. Long term outcomes as measure by eGFR is a tenuous tool to use as a marker of renal damage in the ED because we are not in the business of long term care. Keeping all things acute, the ED may benefit from continued use of creatinine as a measure of reasonable CT use. eGFR may be useful if studied as a short term marker of AKI.