Background Information on Adverse Effects of Iodinated Contrast

Historically, the greatest concern over the use of intravascular iodinated contrast for imaging studies has been the possibility that contrast could have an adverse effect on kidney function. This possible adverse effect has been termed contrast-induced nephropathy (CIN). Concern for CIN is rooted in early literature suggesting a correlation between intravascular iodinated contrast administration and subsequent decreases in kidney function (as measured by serum creatinine tests). However these early studies were limited in several ways: 1) they did not include control groups of patients who did not receive intravascular iodinated contrast, 2) many studies were performed in the era of older high-osmolar contrast media whereas contrast media in current use are universally low- or iso-osmolar, 3) the definition of CIN varied between studies, and 4) many studies evaluated the effects of intra-arterial administration of iodinated contrast rather than intravenous administration, as is commonly performed for non-invasive imaging studies. Given the confounding factors present in these previous studies, the American College of Radiology has adopted the term post-contrast acute kidney injury (PC-AKI) for any sudden deterioration in renal function that occurs within 48 hours following intravascular administration of iodinated contrast and reserves the term contrast-induced nephropathy (CIN) for PC-AKI that is caused by intravascular administration of iodinated contrast.

Recent studies [2-8] suggest that historical concern for CIN after administration of intravenous iodinated contrast was likely overstated. Studies utilizing unmatched control groups published in the last two decades have found no correlation between intravascular contrast administration and subsequent abnormal kidney function. The common limitation of these studies is that patients were not randomized to either receive or not receive iodinated contrast and that the control groups were not matched by patient-specific factors to patients receiving iodinated contrast. These studies are thus limited by selection bias. 

Multiple subsequent studies have since used propensity score adjustment and propensity score matching to correct for selection bias that may have limited prior studies [9-13]. Taken collectively, we can conclude from these studies that intravenous iodinated contrast administration is only rarely associated with acute kidney injury in patients with stable eGFR >30mL/min/1.73m2. These studies have come to conflicting conclusions as to whether intravenous administration of iodinated contrast is associated with acute kidney injury in patients with eGFR < 30 mL/min/1.73m2. 

Many patient-specific factors have been proposed as placing patients at risk for CIN. At present the most studied and accepted risk factor for CIN is pre-existing severe renal insufficiency, as described above. Other proposed risk factors in the literature (but with weaker support) include a history of diabetes mellitus, dehydration, cardiovascular disease, diuretic use, advanced age, multiple myeloma, hypertension, hyperuricemia, and multiple iodinated contrast medium doses in a short time interval. Therefore, screening of patients at risk for CIN is targeted to identify patients with pre-existing severe renal insufficiency.

The incidence and risk factors for contrast-induced nephropathy have not been well-studied in pediatric patients. The effect of intravascular iodinated contrast on kidney function is generally assumed to be similar between children and adults.

Finally, it is important to consider the morbidity and mortality resulting from post-contrast acute kidney injury. The usual course of post-contrast acute kidney injury consists of a transient asymptomatic elevation in serum creatinine. Serum creatinine usually begins to rise within 24 hours of intravascular iodinated contrast medium administration, peaks within 4 days, and often returns to baseline within 7 to 10 days. It is unusual for patients to develop permanent renal dysfunction.

However several studies have shown that in patients who receive intravascular iodinated contrast, those that develop post-contrast acute kidney injury (PC-AKI) tend to have longer hospital stays, higher mortality, and higher incidence of cardiac and neurologic events than patients who do not develop acute kidney injury. These results must be interpreted with caution however: these studies did not include cohorts of patients who did not receive iodinated contrast. It is therefore not possible to conclude if patients who developed acute kidney injury did so as a result of receiving contrast versus alternative causes of acute kidney injury. It also impossible to conclude whether the increased morbidity and mortality seen in patients with PC-AKI is associated with intravascular iodinated contrast exposure or due to some other factor such as the underlying comorbid diseases present in these patients. 

Key Points

1. Historical concern over the association between intravascular administration of iodinated contrast and subsequent decrement in kidney function (contrast-induced nephropathy, or CIN) has been overstated and was based on early studies with a number of limitations.
2. Based on recent studies, we can conclude that intravenous iodinated contrast administration is is only rarely associated with acute kidney injury in patients with stable eGFR >30mL/min/1.73m2. Existing studies have come to conflicting conclusions as to whether intravenous administration of iodinated contrast is associated with acute kidney injury in patients with eGFR < 30 mL/min/1.73m2.
3. The most rigorously studied and accepted risk factor for the development of contrast-induced nephropathy is pre-existing severe renal insufficiency. Screening of patients at risk for contrast-induced nephropathy is therefore targeted to identifying patients with this risk factor.
4. The incidence of contrast-induced nephropathy and risk factors for development of contrast-induced nephropathy have not been well-studied in pediatric patients. The effect of intravascular iodinated contrast on kidney function in pediatric patients is generally assumed to be similar between children and adults.
5. The usual course of post-contrast acute kidney injury is an asymptomatic elevation in serum creatinine that returns to baseline within 7-10 days. It is unusual for patients to develop permanent renal dysfunction. However it should be noted that amongst patients who receive intravascular iodinated contrast, those that develop post-contrast acute kidney injury (PC-AKI) tend to have longer hospital stays, higher mortality, and higher incidence of cardiac and neurologic events than patients who do not develop acute kidney injury. Because the studies demonstrating these adverse outcomes did not include groups of patients who were not exposed to contrast, it is impossible to conclude whether the increased morbidity and mortality seen in patients with PC-AKI is associated with intravascular iodinated contrast exposure or due to some other factor such as the underlying comorbid diseases present in these patients.

+In order to standardize understanding of the effects of nephrotoxic events on kidney function, the diagnosis of acute kidney injury (AKI) should be used according to the Acute Kidney Injury Network criteria. These criteria define specific changes in serum creatinine or urine output within 48 hours of a nephrotoxic event necessary to make the diagnosis of acute kidney injury.

*Estimated glomerular filtration rate (eGFR) is estimated from serum creatinine levels and is considered the best overall index of kidney function. In adults, the CKD-EPI equation is used to estimate GFR. In pediatric patients, the Bedside Schwartz equation is considered the best equation for estimating glomerular filtration rates. This equation requires knowledge of the patient’s height in addition to serum creatinine.

1. ACR Manual on Contrast Media Version 10.3, 2017: 35-46. American College of Radiology
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