Yuanyuan Zhang, Eric P Cohen, Sean V Murphy, Tarek Zaho, Hongbing Liu, Heather Himburg, Michael Patrick Feloney, George William Schaaf, Anthony Atala, J Mark Cline
Evidence supporting these candidate approaches in human radiation-induced renal injury remains limited. Tubular biomarkers, cystatin C, genomic indicators, urinary extracellular-vesicle signatures, and multiparametric MRI have demonstrated potential in other renal disorders or preclinical radiation models, but their RRI-specific kinetics, thresholds, sensitivity, and specificity remain insufficiently established. We therefore propose a multimodal research framework integrating radiation exposure and renal dosimetry, serial renal function assessment, candidate biofluid biomarkers, and functional imaging. Prospective longitudinal validation is required before this framework can be used for routine clinical diagnosis or treatment selection.
BACKGROUND: Radiation-induced renal injury (RRI) is characterized by a prolonged latent phase from radiation exposure to clinical dysfunction. Conventional markers such as serum creatinine and blood urea nitrogen (BUN) may only increase after substantial nephron loss, thereby missing a critical therapeutic window during which renal injury may remain amenable to mitigation.
OBJECTIVE: This review synthesizes emerging strategies for the early, pre-fibrotic detection of RRI, emphasizing molecular damage biomarkers, genomic and epigenetic indicators, and advanced functional imaging techniques that may identify subclinical abnormalities before irreversible fibrosis develops.
CONTENT: Tubular damage biomarkers such as kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) provide sensitive signals that precede functional decline. Filtration markers such as cystatin C may improve early risk stratification compared with creatinine alone. Genomic indicators, including γ-H2AX foci and circulating or urinary microRNAs such as miR-21 and miR-29 capture DNA damage and fibrotic signaling transitions. Advanced imaging modalities-particularly non-contrast multiparametric MRI (diffusion-weighted imaging/intravoxel incoherent motion, arterial spin labeling, blood oxygen level-dependent MRI, and T1 mapping)-demonstrate strong correlations with biopsy-proven fibrosis and microvascular dysfunction. Tc-99m MAG3 renography further reveals split renal function and asymmetrical injury masked by preserved contralateral reserve.
CONCLUSION: Evidence supporting these candidate approaches in human radiation-induced renal injury remains limited. Tubular biomarkers, cystatin C, genomic indicators, urinary extracellular-vesicle signatures, and multiparametric MRI have demonstrated potential in other renal disorders or preclinical radiation models, but their RRI-specific kinetics, thresholds, sensitivity, and specificity remain insufficiently established. We therefore propose a multimodal research framework integrating radiation exposure and renal dosimetry, serial renal function assessment, candidate biofluid biomarkers, and functional imaging. Prospective longitudinal validation is required before this framework can be used for routine clinical diagnosis or treatment selection.