Ankrd1 as a potential biomarker for the transition from acute kidney injury to chronic kidney disease.

Ischemia-reperfusion injury (IRI) is one of the leading causes of acute kidney injury (AKI), predisposing patients to chronic kidney disease (CKD) due to maladaptive renal repair. Nevertheless, the molecular mechanisms and biomarkers that cause maladaptive repair remain unclear. In this study, we used single-nucleus RNA sequencing data from GEO database (GSE139107) to identify molecular markers during the transition from AKI to CKD caused by IRI. Analysis of intercellular crosstalk, trajectory and machine learning algorithms revealed hub cell clusters and genes. Proximal tubule (PT) cells, especially a new cluster (New PT2), significantly interacted with fibroblasts during the transition. The expression levels of hub genes were validated using the bulk RNA-seq data (GSE98622) and further confirmed through RT-qPCR and immunohistochemical analysis in ischemia-reperfusion injury (uIRI) mice. Ankrd1, a hub gene in New PT2, showed sustained upregulation in the proximal tubule in AKI. Compared to the sham-operated group, the expression of Ankrd1 in mice increased at 0.5 days post-reperfusion, peaked at day 1, and remained significantly elevated up to 60 days. This study indicated that the upregulation of Ankrd1 was positively associated with the progression from AKI to CKD and may potentially serve as a valuable biomarker for this transitional process.