By Mario V Fusaro, MD
Faculty Peer Reviewed
There are certain laws in the universe that are just not meant to be broken. One is gravity. Another one is relativity. The third, don’t give contrast to people with bad kidneys. Perhaps the last one is not so much a law as something we seem to be terrified of doing. While recently on service, I had a patient with unexplained right lower quadrant pain. The obvious first or second or fifth step would be a contrast CT. The rub in this case was that this pain was located directly over the site of his newly transplanted kidney and his baseline creatinine was around 2 mg/dL. After an MRI without gadolinium and a myriad of other tests were equivocal, the nephrologist wanted to order a contrast CT scan. As though I’d just come to the realization that there was no Santa Claus, I stared in disbelief. How could the nephrologist of all people want to put the beloved kidney in jeopardy? As I logged on to the ordering screen and navigated my way to the CT contrast order, beads of sweat slipped down my face. My resting tremor sent the cursor into frenzy. With the click of a button, I would be subjecting this gentleman to contrast-induced nephropathy (CIN) for sure. Anxiety-ridden, I cornered the nephrologist and demanded an explanation. Calmly, he informed me of what he believed the patient’s risk of developing CIN was and then delved into some facts and figures. They turned out to be far more optimistic than my own imaginary ones. Still skeptical, I hit the books.
CIN is generally, though variably, defined as an increase in baseline serum creatinine of 25% or > 0.5 mg/dL within 48-96 hours after administration of iodinated contrast. The most established risk factors for CIN are: type of contrast, diagnostic modality, chronic kidney disease (CKD), NYHA class III/IV heart failure (CHF), hypotension, diabetes mellitus (DM) or a combination of these conditions.
The three main classes of contrast agents are high-osmolality (1300-1800 osms), low osmolality (500-850 osms) and iso-osmolality (290 osms). High osmolality agents include: diatrizoate and metrazoate. The low osmolal dyes are: iopamidol, iohexol, ioxilan, and ioprimide. Lastly, iodixanol is an iso-osmolal contrast. The amount of contrast given depends on the study in question. Coronary angiography and computed tomography (CT) of the head, chest, abdomen and pelvis are the main diagnostic modalities in which iodinated contrast is most extensively used and studied. Typical contrast loads for CT are approximately 100 cc depending on the study, with cardiac catheterizations averaging around 260 cc. Some studies suggest that iso-osmolal or low osmolal agents cause less CIN than high osmolality contrast[12-13]. Greater amounts of contrast used are also associated with higher rates of CIN.
Aside from the increased contrast load, those undergoing coronary angiography tend to have worse outcomes by virtue of the fact that they have atherosclerosis and have the potential to shower atheroemboli during the procedure. Following catheterization, CHF, CKD, hypotension and DM are risk factors which carry the highest rates of CIN with incidences ranging from 3-40%[5-7]. CKD and DM also seem to be risk factors for CIN in the setting of CT scans; however the association between CHF and hypotension is less clear. Several recent prospective studies of patients with CKD with or without DM undergoing IV contrast CT scans showed an incidence of CIN that ranged from approximately 5-12%[8-11]. CKD was defined as a GFR of <48 cc/min per 1.73 m2 or baseline serum creatinine of >1.75 mg/dL. In general, the patients more likely to develop CIN were those with DM and/or GFR values of <30 cc/min per 1.73 m2. Interestingly, the patients with solely DM did not have an increased risk of CIN. For patients with GFR values 45-60 cc/min/1.73 m2, the overall risk of contrast nephropathy was 0-5.7%[8,10].
Should the patient be so unfortunate as to experience CIN, what are the consequences? Clinically significant CIN requiring dialysis 30 days after CT with contrast is quite rare. In some observational and prospective studies, the incidence of dialysis within 30 days after exposure to contrast for patients with GFRs of <60 cc/min in the setting of CT scan was 0-0.2% [1,2,10]. Although a reassuring statistic, this finding should be taken with a grain of salt.
The development of CIN portends a bleak outcome for those which it affects over an extended timeframe. In one study, every patient who exhibited CIN with baseline GFR <30 cc/h required permanent dialysis 15 months after the fact. Those that had the same creatinine clearance and did not experience CIN required dialysis in 25% of cases over the same time1. In addition, there are several observational studies showing that there is a significant increase in in-hospital as well as one-year mortality ranging from 6-34% and 12-54%, respectively, in patients who underwent coronary angiography with subsequent serum creatinine increases of >25% from baseline. In these same studies, the incidence of death in hospital as well as at one year was 0.1-7% and 2.7-19.4%, respectively, in those that did not experience CIN. Although unclear whether the association is causal or incidental, these studies clearly show an association between CIN and worsened outcomes. This link underscores the importance of identifying risk factors for development of CIN, forgoing contrast in those who are most predisposed and developing ways to reduce the incidence of CIN.
Many potential methods have been proposed as ways to circumvent or ameliorate CIN and so only a brief overview will be provided here. Treatments tested in randomized controlled trials have included: saline hydration, N-acetyl cysteine (NAC), sodium bicarbonate, dialysis, diuretics, theophylline, and vitamin C. Currently, a popular prophylactic regimen incudes IV saline (1 mL/kg/h) 6-12 hours before and after the study as well as NAC 600-1200 mg BID the day before and day of contrast exposure. Addition of furosemide or mannitol to IV saline may worsen outcomes , theophylline has no benefit and vitamin C has been shown to have a modest but statistically significant benefit in CKD patients. Although these treatments have been studied thoroughly, there is a large amount of disagreement and few randomized controlled trials have shown statistically significant results. Lack of definitive prevention strategies and treatments may be secondary to a fundamental misunderstanding of the pathophysiology, or variables unrelated to contrast.
In one retrospective study of about 32,000 patients who underwent a variety of imaging procedures, without contrast, the authors still found significant rates of apparent AKI (Acute Kidney Injury). For patients with serum creatinine levels <1.2 mg/dL, 27% of them had a >25% rise in serum creatinine following the study. The same increase in serum creatinine was also found in patients with baseline creatinine levels of 2-3 mg/dL at an incidence of 16%. For baselines >3 mg/dL the incidence was 14%. This study suggests that perhaps too much fault is placed on contrast and that maybe the patient’s concurrent diseases are equally to blame.
Perhaps as more and more randomized controlled studies investigating routine imaging with contrast emerge, we will have a clearer picture of who we should be reluctant to give contrast to and how to reduce their risk of AKI. Currently, the strongest predictors of who will develop CIN are patients with: a GFR<30 cc/min, NYHA class III/IV CHF, DM, increased contrast loads and those undergoing coronary angiography. Although the potential for CIN increases with worsening renal function, the CT imaging incidence for even the most at risk does not surpass 13% and is 0-5% with minor to no CKD. The most concerning repercussions in CIN are not necessarily immediate dialysis but long term kidney survival as well as overall mortality. Use of low osmolal and iso-osmolal agents may have a benefit over their high osmolal counterparts. Even though not conclusively substantiated, IV hydration and NAC before and after contrast administration may reduce the incidence of CIN.
Although history and physical reign supreme in identifying a disease process; at times, only an invasive radiologic study will confirm the diagnosis. Sometimes the patient’s best option is not always a safe one and the risks and benefits should be carefully weighed. When possible, non-contrast CT or MRI without gadolinium should be employed to avoid potential CIN or nephrogenic systemic sclerosis. Ultimately, if the results of a study won’t change management, one should probably consider not ordering it.
For the patient discussed earlier, as a last resort, he underwent the CT with iodixanol contrast and the aforementioned saline/NAC prophylactic regimen. He did not succumb to CIN and turned out to have an ascending colitis.
Dr. Fusaro is a 1st year resident at NYU Langone Medical Center
Peer reviewer David Goldfarb, MD, Nephrology Section Editor, Clinical Correlations
Image courtesy of Wikimedia Commons.
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