Erythropoietin receptor upregulation is associated with tubular injury severity in human acute kidney injury.

OBJECTIVE: This study aimed to investigate erythropoietin receptor (EPOR) expression in human AKI and to examine its association with histopathological severity and clinical parameters. METHODS: Renal biopsy specimens from 21 patients with biopsy-confirmed acute kidney injury (AKI) and 12 control kidney tissues from nephrectomy samples were analyzed. EPOR expression was assessed by immunohistochemistry with AI-assisted digital quantification and by immunofluorescence, including co-staining with β-common receptor (βcR) and TUNEL. RESULTS: In human kidney biopsy specimens, EPOR expression was significantly higher in AKI kidneys compared to controls (p < 0.001). Immunofluorescence demonstrated co-localization of EPOR and βcR on tubular epithelial cell membranes. EPOR expression showed significant inverse correlations with stage of AKI (τ = -0.444, p = 0.012), tubular necrosis scores (τ = -0.485, p = 0.005), and acute pathology scores (τ = -0.475, p = 0.005). A significant positive correlation was found between EPOR expression and both red blood cell count (r = 0.490, p = 0.024) and Hemoglobin levels (r = 0.496, p = 0.022). Receiver operating characteristic analysis indicated moderate discriminatory performance of EPOR expression for differentiating AKI severity stages. Consistent with the human data, EPOR protein levels were significantly upregulated in mouse kidneys 24 h after ischemia-reperfusion injury. Single-cell transcriptomic analysis further demonstrated increased EPOR expression in tubular cell populations in AKI. CONCLUSIONS: EPOR expression is upregulated in renal tubular epithelial cells in human AKI and is closely associated with histopathological injury severity and selected clinical parameters, highlighting that EPOR may serve as a marker of tubular stress and injury severity in AKI.