July 2017

Journal Club Thursday July 13, 2017.  Contrast Induced Nephropathy.

Thank you to Harwood for an evening of pastoral scenery and champagne cocktails, and to Marshalla, Graeme, Stanek, Ashley, Oyin, and Anita for their pithy analyses.

Background:  Acute kidney injury (AKI) is associated with overall worse short-term outcomes including dialysis and death.  Uncontrolled studies have suggested IV iodinated contrast material is a risk for contrast material induced nephropathy (CIN), a form of AKI.   Therefore, contrast is a risk for dialysis and death, and should be avoided in patients with pre-existing/past renal dysfunction, or with other high-risk conditions such as diabetes, HIV, HTN, and CHF.      

Or maybe not...


Article 1:  McDonald RJ, McDonald JS, Carter RE et al.  Intravenous contrast material exposure is not an independent risk factor for dialysis or mortality.  Radiology. 2014;273:714-725.

In this retrospective single center study from Mayo, 10,673 patients receiving contrast (C) for abdominal/pelvic/chest CTs were propensity score matched with an additional 10,673 patients who received non-contrast (NC) CTs, to compare outcomes of AKI, 30 day dialysis, and 30 day mortality.   AKI developed in 4.8% (C) vs. 5.1% (NC), dialysis in 0.2% (C) vs. 0.3% (NC), and mortality in 8% (C) vs. 9% (NC).   In “high risk” groups with diabetes, CHF, or acute/chronic renal failure, risks of dialysis and death were higher, but there were no significant outcome differences in high risk patients who received contrast vs. non-contrast CTs.  Yes, if AKI developed, rates of dialysis and death were higher, and rates of dialysis and death were higher in patients with poor baseline renal function, but contrast material exposure was not an independent risk factor for these bad outcomes.

Limitations:  It’s a single center retrospective study.  Unknown why certain high risk patients were chosen to receive contrast.  Causes of mortality are not identified.  Although it’s controversial if anything helps for nephroprotection, authors did not identify what agents (NS, bicarb, NAC) were used or how often.  And, although a large study, only 958 patients with baseline creatinine ≥ 2.0 received contrast.

Bottom line:  IV contrast material for CT scans was not associated with increased risk of AKI, dialysis, or death, even in traditionally high-risk patients.


Article 2:  McDonald RJ, McDonald JS, et al.  Risk of Acute Kidney Injury, Dialysis and Mortality in Chronic Kidney Disease Patients following Intravenous Contrast Material Exposure. Mayo Clinic Proc. 2015;90:1046-1053.

Again from Mayo, a retrospective look at 1220 patients with chronic kidney disease (CKD) Stage III (GFR 30-59) and 491 patients with CKD Stage IV/V (GFR < 30), all receiving IV contrast CTs and propensity score matched with patients receiving non contrast CTs.  Again, rates of AKI, 30 day dialysis, and 30 day mortality were compared between contrast and non-contrast groups.  Many of these patients were included in prior work by McDonald.  For this study, they performed full chart reviews and included a more comprehensive list of clinical variables in the propensity score model in an attempt to improve the strength and accuracy of the conclusions.   For all stages of CKD and across all outcomes, there were no significant differences between groups.  Stage 3 CKD group, AKI 10% (C) vs. 15% (NC); dialysis 0.4% (C) vs. 0.4% (NC); mortality 9% (C) vs. 11% (NC).  In the stage 4/5 CKD group, AKI 21% (C) vs. 20% (NC); HD 1.7% (C) vs. 0.7% (NC); death 18% (C) vs. 19% (NC).


Additional sensitivity analysis evaluating patients with stable pre-CT kidney function, and comparing effects of IV fluid administration at the time of CT were performed, again demonstrated no significant outcome differences between contrast and non-contrast groups.

Limitations reflect the single center, retrospective nature of the trial.

Bottom line:  Specifically in patients with CKD, IV contrast was not associated with increased risk of AKI, 30 day dialysis, or 30 day mortality.


Statistics Pearl:

What’s this Propensity Score Matching (PSM) thing?

PSM is a statistical technique used in observational studies as a way to more closely approach the strength of a randomized control trial.  It attempts to approximate randomization by matching populations from large databases according to patient characteristics, risk factors, and co-morbidities.   This minimizes bias associated with treatment assignments, however PSM only accounts for measured/observable covariates/confounders.  Hidden bias is therefore still likely.   PSM also requires large patient populations.



Article 3:  Hinson, JS et al: Risk of Acute Kidney Injury After Intravenous Contrast Media Administration. Ann Emerg Med 2017;69:577-586.


From Johns Hopkins, a single-center retrospective analysis of nearly 18,000 adult ED patients with baseline creatinine < 4.0, cohorted into three groups:  CT with contrast, CT without contrast, and similar patients without CT.

Primary outcome was incidence of AKI, and secondary outcomes were development of new CKD, dialysis, and renal transplant, all at 6 months. 

Rates of AKI were similar: 10.6% (with contrast) vs. 10.2% (no contrast) vs. 10.9% (no CT).  IV contrast was also not associated with increased risk of the secondary outcomes of CKD, dialysis, or renal transplant at 6 months.


Authors did examine treatment decisions including administration of IV contrast and the administration of IV fluids.  Physicians were less likely to use IV contrast in patients with decreased renal function, and more likely to administer IV fluids when using IV contrast.

Limitations:  Another single center retrospective study.  Most patients were admitted to the hospital, reflecting higher acuity, and may overestimate the incidence of AKI in the general ED population.  Most patients had pre-test creatinine ≤ 1.4.

Bottom line:  IV contrast administration was not associated with increased incidence of AKI, new CKD, need for dialysis or need for renal transplant.


Poll at the end of the evening:  after evaluating these studies, overall attendings feeling more comfortable ordering needed CT scans with IV contrast on patients with GFRs down to around 35.  For potential life threatening diagnoses, attendings consistently support giving contrast (trauma, dissection).   Protection?  Data are all over the place, but most attendings will give IVF. 

Journal Club bottom line:  Understanding of CIN has been complicated by reliance on studies predating the use of low/iso-ismolar contrast, and extrapolation from arterial angiographic studies.  These current 3 well done studies challenge the notion that IV contrast administration for CT scans is a risk for AKI, emergent dialysis, and short term mortality.  A large prospective study is required to definitively end this controversy,  but this literature supports using IV contrast when medically indicated, even in patients with chronic kidney disease, diabetes, and CHF.