Dear pearl of the day readers,
I suppose you could consider this is a part 2 on side effects/toxicity of Iohexol (omnipaque™). This pearl of the day comes at the personal request by one of my coresidents to cover this topic.
Epidemiology
Contrast induced nephropathy (CIN) is an increase in serum creatinine > 25% after administration of IV contrast.
2-10% of patients who received iodinated contrast media suffer acute kidney injury (AKI). The peak of AKI is seen 2-3 days later.
A caveat here is that many times patients will develop AKI from other etiologies after receiving contrast. This makes sense because they needed a CT scan for some clinical indication.
Patients who have pre-existing renal disease or elevated serum Cr are at higher risk for CIN. There are scoring models to see who is at higher risk, but this applies more to interventional procedures requiring higher contrast loads. If you are curious about the scoring systems they can be found here: http://www.kdigo.org/clinical_practice_guidelines/pdf/KDIGO%20AKI%20Guideline.pdf
Side note I found interesting: in patients who had no protein in the urine, only 1% had a Cr>1.7 mg/dL. So no protein in the urine means they probably do not have kidney disease.
Mechanism
The putative mechanism of injury to the kidneys is renal vasoconstriction and direct toxicity to the renal tubular cells, possibly through increased reactive oxygen species.
Chance of recovery
Patients who develop CIN have higher odds of mortality, 1.9. If the CIN requires dialysis, in hospital mortality at one institution increased from 7.1% to 35%.
One British study found that 0.9% of patients developed CKD within 6 months of receiving a contrast loads, compared to 0.17% of patients who developed CKD during the same time period.
So the chances are good the patient will recover.
Treatment
There is no proven treatment; however, pre-treatment with IV or PO fluids is the mainstay practice. In the sense that dehydration is bad for the kidneys, it is reasonable to try to avoid a second hit. However, conflicting data show that there was no difference between fluid pretreatment or not.
Several controversial studies may show that pretreatment with sodium bicarbonate was superior when compared to normal saline (NNT=10); theoretically, this effect is due to decreased free radical formation.
Also theoretically, N-acetyl cysteine (NAC) can help reduce oxidative stress on renal tubular cells. The official journal of the international society of nephrology actually recommends pretreatment in patients at increased risk for CIN with ORAL NAC. High dose oral NAC was shown to decrease the incidence of CIN by 76% in one study. Data is also conflicting here, but trends toward favoring the use of oral NAC in patients at risk for CIN.
Lastly, preliminary data also shows that statins may some how be protective through an unknown mechanism.
Final take home points
Be cautious:
-if the patient is on other nephrotoxic agents
-if the patient has a slightly elevated creatinine compared to baseline (even if it still normal)
-if there is protein in the urine
-if they have a history renal disease
-if eGFR<60
Balance the risk of contrast against the risk of not-performing the correct radiology study. This will be different for every patient.
TR,
W
References
http://www.kdigo.org/clinical_practice_guidelines/pdf/KDIGO%20AKI%20Guideline.pdf
Merten GJ, Burgess WP, Gray LV, et al. Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial. JAMA. 2004;291(19):2328-34.
Patschan D, Buschmann I, Ritter O. Contrast-Induced Nephropathy: Update on the Use of Crystalloids and Pharmacological Measures. Int J Nephrol. 2018;2018:5727309.
Reuben Strayer's response to my post is quite poignant and definitely worth a read:
Despite how penetrated the notion of CIN is in our teaching and practice, and how much time and energy we spend on its supposed prevention, there is considerable controversy as to whether CIN actually exists/occurs.
I’ve pasted conclusions from the latter below. The most important point is if you have a high concern about a dangerous condition and require an IV contrast-enhanced CT scan to rule it in/out, the patient’s creatinine should factor minimally if at all in your decision around whether or not to do the scan. Do the scan.
It is not clear whether contrast is a significant cause of acute kidney injury. According the the American College of Radiologist, “at the current time, there is very little evidence that IV iodinated contrast material is an independent risk factor for AKI in patients with eGFR ≥30 mL / min/1.73m2”. (ACR manual 2017)
We need some large RCTs to settle this issue. There is clearly equipoise on this issue and there should be no barriers to running a RCT.
We should stop using the term “CIN or contrast induced nephropathy” as it implies a degree of causation that simply is not supported by the literature. Post contrast acute kidney injury more appropriately describes what is occurring.
If a patient needs contrast to make an important diagnosis and there isn’t an easily available alternative test, just do the scan. Even if contrast causes acute kidney injury, true patient oriented harms are only seen in a very small number of patients. There is a balance, but as long as the pretest probability of important pathology is higher than the chance of harm (probably less than 1%), the patient will still benefit from the contrast CT.