Understanding the molecular mechanisms associated with the progression of acute to chronic kidney injury is important for the identification of patients at risk of chronic kidney disease (CKD). Building on previous work showing that the transition from acute kidney injury to irreversible renal damage in mice follows a defined transcriptional programme, researchers now show that similar biological processes occur in humans. “We identified two main transcriptional programmes associated with progressive transition to chronic injury or with apparent recovery of the kidney,” says Pietro Cippà. “The transition to chronic injury was unexpectedly similar in human and mouse, suggesting that the fundamental transcriptional programme associated with CKD might be uniform across species.”

To study changes in transcriptional programmes in response to renal injury in humans, Cippà and colleagues performed transcriptome analysis of 163 protocol biopsy samples from 42 kidney transplant recipients at four time points using computational tools originally developed for single-cell RNA sequencing. “We took advantage of machine learning techniques specifically developed to characterize single cell heterogeneity in complex tissues to study ‘single patient’ heterogeneity in a complex clinical setting, and generated a global map of kidney injury progression from the first minutes after reperfusion to fibrosis,” explains Cippà. Their analyses showed a rapid upregulation of immediate-early genes involved in stress responses following reperfusion in all patients, after which transcriptional signatures diverged in accordance with progression to kidney injury or renal recovery. “Our study represents a starting point for many potential applications,” says Cippà. “Although the predictive relevance of our data needs to be verified and more focused analyses of the underlying biology are required, use of such strategies might help identify fundamental cellular processes that underlie CKD and define novel therapeutic strategies.”