Journal Club Podcast #40: August 2017
A brief discussion on contrast-induced nephropathy and some of the evidence that suggests it may be as real as Sasquatch himself...
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Article 1: Hinson JS, Ehmann MR, Fine DM, Fishman EK, Toerper MF, Rothman RE, Klein EY. Risk of Acute Kidney Injury After Intravenous Contrast Media Administration. Ann Emerg Med. 2017 May;69(5):577-586.e4. Answer Key.
Article 2: Mitchell AM, Jones AE, Tumlin JA, Kline JA. Incidence of contrast-induced nephropathy after contrast-enhanced computed tomography in the outpatient setting. Clin J Am Soc Nephrol. 2010 Jan;5(1):4-9. Answer Key.
Article 3: McDonald JS, McDonald RJ, Carter RE, Katzberg RW, Kallmes DF, Williamson EE. Risk of intravenous contrast material-mediated acute kidney injury: a propensity score-matched study stratified by baseline-estimated glomerular filtration rate. Radiology. 2014 Apr;271(1):65-73. Answer Key.
Article 4: McDonald JS, McDonald RJ, Comin J, Williamson EE, Katzberg RW, Murad MH, Kallmes DF. Frequency of acute kidney injury following intravenous contrast medium administration: a systematic review and meta-analysis. Radiology. 2013 Apr;267(1):119-28. Answer Key.
It was a clear black night, a clear white moon...and you're stuck working in EM-2 instead of out regulatin'! One of your patients is Ms. Z, a 52-year old woman with left lower quadrant abdominal pain. She's quite tender and has some localized guarding, but no rebound. Her WBC is 14.5. You're worried about diverticulitis, possibly with rupture and an abscess, and would like to get a CT scan, but her creatinine is 1.7, which is her baseline. Additionally, she has a history of diabetes and hypertension, and you worry about causing contrast-induced nephropathy (CIN) if you give contrast for the CT.
Your attending assures you that there's no such a thing as CIN, that it's as made up as Santa Claus and the Easter Bunny (EmLitofNote: The Latest Myth: Contrast-Induced Nephropathy; EMCrit: Do CT Scans Cause Contrast Nephropathy). As you fight back the tears, your childhood fantasies destroyed, you call the radiologist to discuss what to do. The radiologist shares your concerns and suggests that in this "not overly skinny" woman, contrast shouldn't be necessary.
Lo and behold, the CT shows uncomplicated diverticulitis, and Ms. Z goes home on oral antibiotics, her remaining nephrons safe and secure. But as you end your shift, eyes heavy with fatigue, you wonder: was your attending right about CIN (and the poor little Easter Bunny), or was the radiologist right to be concerned? You head home, crash, wake up refreshed, and begin to search the literature…
Population: Adult patients undergoing computed tomography (CT) scan
Intervention: Administration of intravenous contrast for enhancement of CT scan
Comparison: No contrast administration for enhancement of CT scan
Outcome: Acute kidney injury, chronic kidney disease, need for dialysis, mortality
An article published in a recent issue of Annals of Emergency Medicine (Hinson 2017) was chosen as the impetus for this journal club. A meta-analysis referenced in this article, along with two primary research studies, were chosen for inclusion as well.
Iodinated contrast media was once cited as the third most common cause of iatrogenic acute kidney injury (Hou 1983). Previous research on the incidence of contrast-induced nephropathy (CIN) associated with intravenous contrast for CT scans in the ED has found the rate to be around 11%, with much lower rates of severe renal failure (1%) and death due to renal failure (0.6%) (McDonald 2014). Other studies have reported similar rates (Mitchell 2007, Mitchell 2012).
The problem with these cohort studies is that while they demonstrate the incidence of AKI in patients receiving IV contrast, they do not necessarily establish contrast as the cause of the AKI. Patients receiving IV contrast typically have some issue requiring them to undergo CT scanning or angiographgy, and some percentage of these patients would develop AKI independent of contrast administration. As a result, several observational studies have been undertaken to compare the incidence of AKI and other outcomes in patients receiving contrast to the incidence in patients not receiving contrast.
While some older studies have demonstrated an increased incidence of AKI among patients receiving IV contrast when compared with controls (Heller 1991, Polena 2005) these studies have failed to control for potential confounders. Studies that have controlled for such confounder, typically using propensity score matching, have found no increased incidence of AKI, severe kidney failure, or death due to renal failure compared to patients not receiving contrast (McDonald 2014, Hinson 2017). A meta-analysis of all such studies, performed in 2013, similarly failed to demonstrate a statistically significant increase in the incidence of AKI (McDonald 2013).
While the bulk of data thus far does not suggest a clear association between IV contrast administration and acute kidney injury (AKA CIN), no randomized controlled studies have performed up to this point. While more recent studies have used methods such as propensity matching to help control for known confounding factors, these studies are not able to control for unknown confounders, and similarly have not controlled for potentially renal protective interventions undertaken after contrast administration (e.g. IV fluid administration and bicarbonate administration, withholding of potentially nephrotoxic drugs). It would therefore be difficult to advocate for a change in clinical practice without such randomized controlled trials.
There have been several barriers to performing such studies, including the assumption that IV contrast is harmful. The current evidence may help break that barrier, establishing that there is clinical equipoise regarding this issue, but other issues remain. Perhaps the most significant is the potential harm in withholding IV contrast in patients undergoing CT who would benefit from contrast enhancement, making it unethical to randomize patients to a non-contrast arm in such a study. Unfortunately, until further evidence is available, it seems prudent to consider withholding IV contrast in patients felt to be at high risk of developing AKI, with the caveat that in some emergent cases (i.e. possible aortic dissection), the risks of withholding contrast may outweigh the risks of developing kidney injury.