Decoy Receptor 2 as a Cell Cycle Arrest Biomarker for Predicting Renal Recovery Following Acute Kidney Injury

Abstract

Renal recovery following acute kidney injury (AKI) is a key determinant of long-term prognosis, while non-recovery significantly increases the risk of chronic kidney disease and progression to end-stage renal disease. Although cell cycle arrest is implicated in renal non-recovery and fibrosis, its association with decoy receptor 2 (DcR2) remains unclear. In this study, we evaluated 139 patients with biopsy-confirmed AKI, defining renal non-recovery as a ≥ 50% increase in baseline serum creatinine (Cr) or the initiation of dialysis. Patients were divided into recovery (n = 79) and non-recovery (n = 60) groups. Urinary DcR2/creatinine (uDcR2/Cr) levels were significantly higher in non-recovery cases, with an area under the curve of 0.733 and a diagnostic cut-off of 378 ng/gCr. Elevated uDcR2/Cr predicted poor renal survival and was independently correlated with non-recovery. In mouse models of ischemia–reperfusion-induced AKI, increased urinary and tubular DcR2 levels were also associated with impaired recovery. Proteomics analysis revealed GSK3b enrichment in cell cycle pathways. Functional studies showed that DcR2 mediated cell cycle arrest through GSK3b/cyclin D1 signalling. In conclusion, DcR2 functions as a biomarker of cell cycle arrest and renal recovery, offering both diagnostic and mechanistic insights, and may serve as a potential therapeutic target in AKI.