Chronic kidney disease (CKD) is a progressive and heterogeneous condition affecting more than 1 in 7 adults in the United States and approximately 10-15% of adults worldwide, reflecting its substantial burden on public health. Current clinical classifications offer limited insight into the molecular mechanisms driving CKD progression, as functional measures such as estimated glomerular filtration rate do not capture the underlying biological heterogeneity arising from inflammatory, metabolic, and fibrotic processes. Patients with similar clinical profiles may therefore follow different disease trajectories, highlighting the need for transcriptomic approaches to identify mechanistic subtypes. Identifying molecular signatures, including gene expression patterns, may support more precise subtype classification of CKD and reveal distinct pathophysiological pathways to inform therapeutic strategies. To address this gap in knowledge, we generated a CKD model in male rats by combining a 21-day adenine diet with unilateral nephrectomy. CKD development was confirmed by elevated serum creatinine, reduced glomerular filtration rate as an index of renal function, and increased expression of renal fibrosis markers assessed by qPCR. We performed genome-wide RNA-seq analysis of the renal cortex followed by bioinformatic analysis to identify differentially expressed genes and enriched pathways. Dataset variation was assessed using principal component analysis and Pearson correlation plots to evaluate inter- and intragroup variability. A low-count threshold, based on RPKM (reads per kilobase of transcript per million mapped reads) values, was applied, and volcano plots were generated to visualize genes that were up- and down-regulated in CKD animals compared with controls. KEGG pathway enrichment analysis (p- and q-value thresholds of 0.05) identified significantly affected pathways, grouped into five categories: Cellular Processes, Metabolism, Organismal Systems, Human Diseases, and Environmental Information Processing. In total, 107 pathways were significantly enriched in CKD animals compared with controls. These included pathways associated with metabolic alterations, immune dysregulation, and cellular stress responses, such as NF-κB, MAPK, and PI3K–Akt signaling. Overall, these results provide a comprehensive molecular map of CKD-associated transcriptomic alterations in this adenine-diet unilateral nephrectomy model and highlight disease-related pathways that may represent potential therapeutic targets. Supported by an IOER Award 06-25-05 This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
D'Onofrio et al. (Fri,) studied this question.