Biomarker-dependent detection of contrast-associated acute kidney injury after intra-arterial contrast procedures: an exploratory randomized trial

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• Picked for Biochemistry (medical) (top studies of the week, 8 November 2026): Direct comparison of renal biomarkers and diagnostic definitions

Abstract

BACKGROUND: Contrast-associated acute kidney injury (CA-AKI) remains a controversial clinical entity, partly because incidence estimates vary according to the diagnostic criteria and biomarkers used. Serum creatinine-based definitions may underestimate early functional renal impairment after contrast exposure, whereas cystatin C has emerged as a more sensitive early biomarker of glomerular filtration changes. This study aimed to evaluate how biomarker selection influences CA-AKI detection and interpretation of preventive strategies after intra-arterial contrast procedures. METHODS: This prospective, randomized, single-blind exploratory trial included 76 patients with peripheral arterial disease undergoing elective intra-arterial contrast-enhanced vascular procedures, most of which were diagnostic angiographic examinations. Participants were stratified according to baseline renal function and randomized to receive either standardized hydration alone or hydration plus high-dose atorvastatin and N-acetylcysteine. CA-AKI was assessed using two predefined definitions: historical creatinine-based criteria (≥ 25% or ≥ 0.5 mg/dL increase within 72 h) and cystatin C-based criteria (≥ 10% increase within 24 h). Diagnostic concordance and biomarker-dependent differences in event ascertainment were evaluated. RESULTS: Substantial diagnostic discordance was observed between creatinine- and cystatin C-defined CA-AKI, with no overlapping cases and poor agreement between biomarkers (κ = 0.07). Creatinine-based criteria identified 4 CA-AKI events, whereas cystatin C identified 7 additional early functional injury cases. Biomarker-dependent differences in event detection varied across renal function strata, particularly among patients with preserved baseline renal function. Low event rates using creatinine-based criteria limited definitive assessment of preventive efficacy. Exploratory analyses suggested that biomarker selection influenced the apparent magnitude and direction of treatment-effect estimates. CONCLUSIONS: CA-AKI ascertainment after intra-arterial contrast exposure is strongly biomarker-dependent. Historical creatinine-based definitions may underestimate early functional renal impairment and influence interpretation of preventive strategies. These findings highlight the importance of endpoint selection in CA-AKI clinical trials and support further investigation of sensitive functional biomarkers in larger prospective studies. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials (ReBEC), RBR3h2gv8r (Universal Trial Number U1111-1277-3145), registered on 31 March 2023 retrospectively registered.

Abstract as published, via PubMed.