According to the 2025 American College of Radiology (ACR) Manual on Contrast Media, there is insufficient evidence to require delaying repeat intravenous (IV) iodinated contrast administration based on a specific time interval, including 24 hours, and insufficient evidence to define a contrast volume threshold beyond which additional contrast should not be given within that period. A dose-toxicity relationship has been described for intra-arterial cardiac angiography, but not for IV iodinated contrast at usual diagnostic doses. Although multiple IV doses within a short interval (24 hours) have been proposed as a potential risk factor, available studies were not designed to demonstrate higher risk compared with one or no doses, and interim serum creatinine measurements between closely spaced studies are unlikely to be useful. Repeat IV contrast administration is therefore treated as a clinical risk-benefit decision, with greater caution in patients with advanced chronic kidney disease (CKD) or acute kidney injury (AKI) rather than governed by a numeric limit. For oral enteric contrast, ACR guidance addresses indications, formulations, and adverse effects such as aspiration, hyperosmolar fluid shifts, mucosal irritation, diarrhea, rare direct toxicity, and thyroid effects, but does not define a maximum dose or time-based restriction. However, the manual does note that approximately 1% to 2% of enteric iodinated contrast may be systemically absorbed, and that allergic-like reactions can occur despite the small absorbed amount. Overall, the ACR acknowledges the lack of evidence to define maximum contrast volumes or dosing intervals and instead emphasizes clinical risk-benefit assessment. [1]
A 2018 review discusses defining and operationalizing the maximum amount of iodinated contrast that can be safely administered during a cardiovascular procedure to reduce the risk of contrast-induced acute kidney injury (CI-AKI). Rather than a fixed universal threshold, the paper emphasizes patient-specific limits based on baseline renal function and body size, most notably the maximum allowable contrast dose (MACD), calculated as 5 mL × body weight (kg) divided by serum creatinine (mg/dL), with an upper cap of 300 mL. Across multiple retrospective and prospective cohort studies, administration of contrast volumes exceeding the MACD during a single procedure was consistently associated with a substantially higher incidence of CI-AKI (on average about 24% compared with 6% when the MACD was not exceeded) as well as increased risks of dialysis requirement, in-hospital mortality, bleeding, and cardiac events. Importantly, this association persisted after adjustment for comorbidities, establishing excessive contrast volume as an independent and modifiable risk factor. [2]
The review further refines the concept of “maximum contrast” by highlighting relative dosing metrics that account for renal function, particularly the contrast volume-to-eGFR or creatinine clearance ratio. Evidence demonstrates a graded, time-linked increase in CI-AKI risk as this ratio rises, with the lowest risk observed when contrast volume is kept below the patient’s MACD and, ideally, when the contrast volume-to-eGFR ratio is <1.0. Exceeding these limits during a single procedural exposure markedly increases CI-AKI incidence, especially in patients with chronic kidney disease, diabetes, or acute coronary syndromes. On the basis of these data, the authors advocate for a priori calculation of MACD and relative contrast ratios before each procedure, strict intraprocedural adherence to these limits, and consideration of staged procedures over separate time periods when diagnostic or therapeutic goals would otherwise require contrast volumes beyond the calculated maximum for a single exposure. [2]
Reviews on contrast-induced nephropathy indicate that large contrast volumes and multiple injections within 72 hours are associated with an increased risk of renal injury. While it is recognized that no definitive maximum safe dose has been established, research in coronary angiography patients has demonstrated that low-osmolar contrast volumes exceeding 30 mL significantly increase nephropathy incidence, with each additional 5 mL increment raising the risk by 65%. Intra-arterial administration is more nephrotoxic than intravenous delivery due to higher acute intrarenal concentrations. Consequently, emphasis is placed on using the minimal effective dose, avoiding repeat contrast exposure within 72 hours whenever possible, and considering alternative imaging modalities for high-risk patients. [3], [4]
A 2024 animal study in rats evaluated repeat intravenous iodinated CT contrast or gadolinium MR contrast given 2, 4, or 24 hours after an initial iodinated contrast dose. Repeated CT contrast administration at all intervals produced significantly higher serum creatinine compared with single-dose control (p<0.001), while cystatin C and malondialdehyde levels did not differ. mRNA and protein expression of kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin were not significantly changed, and no significant histologic injury was observed. Additional gadolinium contrast after CT contrast did not significantly alter serum creatinine, cystatin C, malondialdehyde, or kidney injury biomarkers compared with single-dose CT contrast. The authors concluded that an interval likely exceeding 24 hours may be needed between repeated contrast-enhanced CT examinations to avoid renal function deterioration, whereas performing contrast-enhanced MRI the same day as contrast-enhanced CT did not produce clinically significant kidney injury in this model. It is important to note that the inherent limitations of an animal study limit the direct translation of these findings to human clinical practice. [5]