In Practice
The Controversy of Contrast-Induced Nephropathy With Intravenous Contrast: What Is the Risk?

https://doi.org/10.1053/j.ajkd.2019.05.022Get rights and content

Contrast-induced nephropathy (CIN) has long been observed in both experimental and clinical studies. However, recent observational studies have questioned the prevalence and severity of CIN following intravenous contrast exposure. Initial studies of acute kidney injury following intravenous contrast were limited by the absence of control groups or contained control groups that did not adjust for additional acute kidney injury risk factors, including prevalent chronic kidney disease, as well as accepted prophylactic strategies. More contemporary use of propensity score–adjusted models have attempted to minimize the risk for selection bias, although bias cannot be completely eliminated without a prospective randomized trial. Based on existing data, we recommend the following CIN risk classification: patients with estimated glomerular filtration rates (eGFRs) ≥ 45 mL/min/1.73 m2 are at negligible risk for CIN, while patients with eGFRs < 30 mL/min/1.73 m2 are at high risk for CIN. Patients with eGFRs between 30 and 44 mL/min/1.73 m2 are at an intermediate risk for CIN unless diabetes mellitus is present, which would further increase the risk. In all patients at any increased risk for CIN, the risk for CIN needs to be balanced by the risk of not performing an intravenous contrast-enhanced study.

Section snippets

Clinical Vignette

A 60-year-old man presented to the emergency department with sudden onset of right anterior chest pain. The pain was sharp in nature, exacerbated with breathing, and there were no symptoms of fever, hemoptysis, or shortness of breath. The patient also provided a history of right calf pain for the past 3 days. Medical history includes hypertension and diabetes mellitus (DM) each of 10 years’ duration, and chronic kidney disease (CKD; baseline serum creatinine [Scr], 1.9 mg/dL). Physical

Randomized Studies Demonstrating Differences in AKI After Contrast Exposure

Support for the position that intravenous CM can be nephrotoxic comes from prospective randomized controlled trials (RCTs) demonstrating different AKI rates between groups who received different CM or who were or were not exposed to a prophylactic intervention. Risk factors for AKI other than type of CM or prophylactic intervention should be balanced in RCTs, so differences in AKI incidence should be due to contrast nephrotoxicity. RCTs have demonstrated that high-osmolal CM have a greater risk

Comparison of CIN With Intra-arterial and Intravenous Contrast Administration

Those who propose that CIN from intravenous CM is overstated argue that this conclusion has been inappropriately extrapolated from studies investigating AKI following intra-arterial CM exposure.9 Given differences in baseline patient comorbid conditions and the procedural risks of coronary angiography, it is intuitive to expect a higher AKI rate following CM exposure with coronary angiography compared to CECT.21, 22 Numerous studies of patients undergoing coronary angiography have demonstrated

CECT Studies of CIN Without Control Groups

Initial studies of AKI following intravenous CM were conducted, with rare exception, without control groups (patients who underwent similar radiologic procedures without CM administration).34, 35, 36, 37 These reports identified CKD as an independent risk factor for CIN, and that DM was an additional risk factor when coupled with CKD. Many of these studies focused on hospitalized patients due to the necessity of obtaining 24- to 72-hour postscan Scr data. The focus on hospitalized patients had

CECT Studies of CIN With Nonrandomized Control Groups

The importance of controls in CM exposure studies was largely ignored until the publication of 2 landmark observational studies.39, 40 Newhouse et al39 performed a retrospective analysis of 32,161 hospitalized patients with serial Scr values on 5 consecutive days and with no CM exposure to determine the frequency of Scr level changes over time.39 During the 5-day period, a change in Scr level of at least 25% or 0.4 mg/dL was observed in a significant proportion of patients with both normal and

CECT Controlled Studies of CIN With Propensity Score Adjustments

Given the imbalance in confounding covariates and selection bias between CM and control populations, the ideal approach to determine CIN following intravenous contrast would be an RCT in patients undergoing CT with or without CM enhancement, which would ensure balanced comorbid conditions between groups and nonbiased randomization. For ethical and logistical reasons, it is unlikely that such RCTs will be performed. Recognizing these limitations, several investigators performed studies using

Mortality, Dialysis, and CKD With CIN

AKI is associated with risks for CKD development, progression, and all-cause mortality.56, 57, 58, 59, 60 These observational studies are supported by experimental studies of AKI that provide plausible biological mechanisms for clinically relevant outcomes.61, 62, 63, 64 In a population that has developed CIN, there is a debate of whether this is associated with a clinically relevant longer-term adverse outcome. Several studies have demonstrated increased in-hospital and long-term mortality,

Summary and Recommendations

It is important to determine with as much precision as possible the true risk for nephrotoxicity from intravenous CM exposure. If the risk is overestimated, patients who could clinically benefit from CECT would be deprived of that benefit and there would be needless application of resources to prevent against this complication. If the risk is underestimated, patients could be exposed to a nephrotoxic insult with the potential for adverse clinical outcomes, including progression of CKD.

Initial

Review of the Clinical Vignette

The patient was suspected of having a pulmonary embolism and a decision was made to proceed with CTA with intravenous CM. Because the patient was considered high risk for CIN, he received normal saline solution (240 mL over 1 hour) before contrast exposure, which was continued at 100 mL/h for 6 hours after the procedure. CTA identified a segmental pulmonary embolism. The following day, Scr level was 2.5 mg/dL with urine output of 1,100 mL and then started to decline, returning to an Scr level of 1.9

Article Information

Authors’ Full Names and Academic Degrees

Michael R. Rudnick, MD, Amanda K. Leonberg-Yoo, MD, MS, Harold I. Litt, MD, Raphael M. Cohen, MD, Susan Hilton, MD, and Peter P. Reese, MD, MSCE.

Support

There was no additional support provided for the work described in this article.

Financial Disclosure

The authors declare that they have no relevant financial interests.

Other Disclosures

Dr Reese serves as an AJKD Associate Editor; he was entirely recused from the manuscript consideration process.

Peer Review

Received November 12, 2018, in response to an invitation from the journal. Evaluated by 2

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