Once upon a time, there was a man called Dom Quixote. He was a huge book fan, but life was not a big fan of him. One day he started to live his books, because it was all that life had left for him to live. His mind started to believe the fairy tale was real. Suddenly, Dom Quixote and his friend Sancho were fighting windmills as if they were giants and I think you know the rest of the history…
There is a fantastic article by Kress called “The ten diseases that are not true diseases.” Despite the fact he didn’t listed cant contrast induced nephropathy (CIN) as one of those diseases, I really think he should have. To be honest, is CIN a giant or a windmill?
First things first. How do we define CIN? Well, when we don’t know for sure we create lots of definitions. The majority of clinical trials use an increase in serum creatinine of 0.5mg/dl or 25% after 48-72h of contrast exposure. Yeah, just this simple! Meaning if you do a contrast enhanced CT today and later tonight have both kidneys removed, your renal failure (two days from today) will be considered CIN by our clinical trials standards.
Ok, let’s take the confounders out our way. After an elective contrast enhanced CT in outpatients with an eGFR<60ml/min/1.73m², only 0.4% will experience a rise in serum creatinine of 0.5mg/dl or more. But gimme the real deal, dude! Intra-arterial contrast administration! You mean percutaneous coronary intervention, pal? Well, among 7586 patients who underwent PCI in the famous Rihal paper, 3.3% developed CIN, and only 20 patients (0.2%) required dialysis. Remembering that all patients were analyzed in this paper, including those with acute MI and shock.
The giant looks little small now, doesn’t he?
How about the real sick patients, I mean, this is an ICU blog for God’s sake! If we use the criteria of 25% rise in serum creatinine, the incidence of CIN in ICU is something around 17%. Yeah! That’s what I’m talking about!
But wait! Let me ask you one silly question: Imagine you’re on a 10-bed ICU, would you be surprised if 2 patients had a rise of at least 25% in their serum creatinine in the next 48-72h? Well, I wouldn’t! Sepsis, hypotension, vancomycin, amikacin, steroids, surgery, fluids, ECMO, ARDS, obstructed vesical catheters…And after all of this, 100ml of contrast! In the middle of this terrifying war, is contrast the giant?
Ok, I understand your point of view, but we will never run a randomized controlled trial where critically ill patients will be randomized to contrast vs non-contrast exam. That’s the way it is. What we can do is try to analyze this with a propensity score model. Propensity score is like statisticians’ Tinder, where you have a patient who underwent a contrast enhanced exam and look for a similar patient who didn’t and match them to compare. That’s the tool we can use to solve our problem! The propensity, not the Tinder. Although Tinder can solve lot of other problems. Anyway…That was exactly what McDonald did few years ago, and found that there were no difference in CIN between groups. He was telling us that maybe CIN is just a windmill.
Early this year the large AMACING Trial (already discussed here) was published, and found no benefits in pre-hydration to prevent CIN in elective exams. The evidence regarding other interventions, like bicarbonate, acetylcisteine, dialysis and ischemic conditioning, is that they also don’t seem to work. The reason that no intervention showed efficacy in CIN prophylaxis is probably because we are using a sword to kill a windmill. Even if contrast is not a windmill, it is just one tiny soldier in a world war.
To be honest, I am not saying CIN doesn’t exist. Neither I’m saying it does. What I am saying is that we can’t arbitrary make the erroneous assumption that contrast = acute kidney injury. When a patient has MRSA infection, do you give up vancomycin only because his eGFR<30ml/min/1.73m²? If the patient really needs a contrast enhanced exam, we should not give up on it. If this giant is not a windmill, he is probably a dwarf.
1. Depuydt PO, Kress P, Salluh JIF. The ten “diseases” that are not true diseases. Intensive Care Med. 2016; 42:411-4.
2. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney inter., Suppl. 2012; 2: 1–138.
3. Weisbord SD, Mor MK, Resnick AL, Hartwig KC, Palevsky PM, Fine MJ. Incidence and outcomes of contrast-induced AKI following computed tomography. Clin J Am Soc Nephrol. 2008;3:1274–1281.
4. Rihal CS, Textor SC, Grill DE, Berger PB, Ting HH, Best PJ, Singh M, Bell MR, Barsness GW, Mathew V, et al. Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention. Circulation. 2002;105:2259–2264
5. Clec’h C, Razafimandimby D, Laouisset M, Chemouni F, Cohen Y. Incidence and outcome of contrast-associated acute kidney injury in a mixed medical-surgical ICU population: a retrospective study BMC Nephrol. 2013; 14(1).
6. Valette X, Parienti JJ, Plaud B, et al. Incidence, morbidity, and mortality of contrast-induced acute kidney injury in a surgical intensive care unit: a prospective cohort study. Journal of Critical Care. 2012;27(3):322.e1–322.e5
7. McDonald, R.J., McDonald, J.S., Bida, J.P., Carter, R.E., Fleming, C.J., Misra, S. et al, Intravenous contrast material-induced nephropathy: causal or coincident phenomenon?. Radiology. 2013;267:106–118
8. Nijssen EC et al. Prophylactic Hydration to Protect Renal Function from Intravascular Iodinated Contrast material in Patients at High Risk of Contrast-Induced Nephropathy (AMACING): A Prospective, Randomised, Phase 3, Controlled, Open-Label, Non-Inferiority Trial. Lancet 2017; S0140 – 6736(17)30057 – 0.