This is the largest reported retrospective cohort study examining the risk of contrast-induced nephropathy in patients with acute stroke. We found that the incidence of AN in the contrast-exposed group did not exceed the incidence of AN in the nonexposed group. In fact, after adjusting for possible confounders, the contrast-exposed group had a lower risk for developing AN than the nonexposed group. The addition of contrast used for conventional angiography after CTA/CTP did not increase the incidence of AN.
Contrast-induced nephropathy is the third most common cause of renal failure, accounting for 11% of cases of hospital-acquired renal insufficiency.4
The most commonly accepted definition of CIN is an increase in creatinine of ≥25% of the baseline value or an absolute increase of ≥0.5 mg/dL in creatinine above the baseline value within 48–72 hours of exposure to contrast material.8
Serum creatinine level typically peaks 3–5 days after contrast administration and returns to baseline within 1–3 weeks.20
Several conditions increase the risk for CIN. Pre-existing renal disease with an elevated level of serum creatinine level is the primary risk factor for developing of CIN.8
A baseline test of renal function is strongly recommended by the American College of Radiology and European Association of Uroradiologists as a way to assess the risk of CIN.6
Expanded use of CT-based multimodal imaging has been constrained by concerns about potential nephrotoxicity, particularly because time pressures in evaluating patients with acute stroke can necessitate making decisions regarding contrast administration in the absence of a baseline creatinine value. Smith et al1
demonstrated that waiting for the baseline creatinine level resulted in lengthy delays (average time, 73.3 ± 51 minutes) in patients with acute stroke. Because acute stroke management protocols seek to minimize the time from symptom onset to thrombolytic delivery, any delay in the process of evaluation is detrimental. This study supports the safety of intravenous contrast agents in patients with acute stroke independent of baseline eGFR when standard prophylactic measures are taken (including the use of low-osmolar contrast agents, adequate intravenous hydration, and pre-treatment with N
-acetylcysteine in high-risk patients).
A combination of several mechanisms is thought to be responsible for the development of CIN. Renal vasoconstriction and direct tubular injury are thought to be the main factors. The medullary portions of the kidney are particularly vulnerable to reductions in blood flow, given the long length of the vasa recta, the low levels of partial pressure of oxygen encountered, and the high oxygen requirements of the renal tubules responsible for salt reabsorption. Direct tubular injury by contrast agents may be exacerbated by renal vasoconstriction.21
The incidence of CIN might have been overestimated by extrapolating data from cardiology patients who underwent conventional angiography. Local renal hypoxia may be aggravated by other complications frequently found in this population of patients, such as transient reduced cardiac output and perturbations in the pulmonary ventilation-perfusion relationship.
Our data are consistent with the low rates of CIN reported after CTA/CTP in patients with stroke.17,18,22
The incidence of CIN might have been overestimated in previous studies though. As many as 27% of hospitalized patients with baseline creatinine values between 0.6 and 1.2 mg/dL and 16% of those with baseline creatinine values of >2.0 mg/dL would be included under the definition of CIN (a 25% increase in creatinine compared with baseline level) without receiving contrast material. Very few studies have used control groups to compare the risk of AN in patients receiving and not receiving iodinated contrast.12,13
Pre-existing renal dysfunction is the most important risk factor for the development of CIN. Although an elevated baseline creatinine level is a marker of pre-existing nephropathy, it is not reliable enough to identify patients at risk for CIN.8
Creatinine clearance is the most reliable way to evaluate renal function. Its estimation can be easily performed by using the Modification of Diet in Renal Disease Equation.15
The risk of CIN increases as the eGFR falls, particularly below 60 mL/min/1.73 m2
Our study is the first retrospective cohort study to stratify on the basis of baseline renal function.
There are limitations to our study. Patients undergoing the CTA/CTP were highly selected, as evidenced by the higher rates of diabetes, congestive heart failure, and renal insufficiency in the control population. We believe that this recapitulates routine clinical practice, however. We did not collect data on compliance with recommendations for renal protection after contrast administration (including intravenous hydration and pretreatment with N-acetylcysteine), though given the acute nature of the studies, hydration was likely the only potential intervention. Because of the low number of cases, the results are not generalizable to patients with severe renal insufficiency (eGFR <30).