Systematic Review Details RNA Sequencing Discoveries in Diabetic Kidney Disease

A systematic review of twenty-eight RNA sequencing studies has identified widespread transcriptomic dysregulation across human tissues in diabetic kidney disease, demonstrating consistent convergence on key biological pathways despite limited overlap at the individual gene level. While individual transcriptomic markers varied substantially between investigations, differential expression analyses recurrently implicated inflammatory and immune signalling, fibrosis and extracellular matrix remodelling, mitochondrial and metabolic dysfunction, altered intercellular communication, and cellular stress and repair pathways.

Diabetic kidney disease represents a leading cause of chronic kidney disease and end-stage kidney disease globally. Although affected individuals frequently share clinical risk factors, patients display substantial variability in disease susceptibility and progression, indicating that molecular mechanisms contribute beyond traditional clinical predictors. RNA sequencing technologies provide an unbiased method to characterise disease-associated transcriptomic alterations, yet earlier findings remained fragmented across distinct tissues, RNA classes, and analytical platforms without prior systematic synthesis.

To synthesise the existing transcriptomic evidence, investigators conducted a systematic review following PRISMA 2020 guidelines. The researchers searched PubMed, Embase All, and Web of Science Core Collection records from 2006 to April 2025, followed by a top-up search extending through May 2026. The search targeted studies comparing transcriptomic profiles between diabetic individuals with and without diabetic kidney disease, as well as across defined disease progression phenotypes.

Eligible investigations were restricted to bulk, single-cell, long-read, or small RNA sequencing approaches conducted in human-derived tissues or biofluids, including plasma, serum, and urine. The review authors extracted data regarding study design, tissue source, RNA species, sequencing methodology, differential expression findings, and pathway analyses. Study quality was systematically evaluated using the Newcastle–Ottawa Scale alongside a specialised reporting checklist designed for RNA sequencing research.

The twenty-eight included studies analysed a diverse collection of human biological samples, encompassing kidney biopsy tissue, blood-derived specimens, urinary extracellular vesicles, urine sediment, and patient-derived fibroblasts. The research spanned multiple RNA classes, including messenger RNAs, long non-coding RNAs, microRNAs, piwi-interacting RNAs, and other small non-coding RNAs. In addition, single-cell and spatial transcriptomic platforms identified cell-type–specific injury and fibrotic programmes that could not be discerned in bulk sequencing analyses.

Cross-study integration remained constrained by substantial heterogeneity in diagnostic definitions of diabetic kidney disease, tissue sources, RNA classes, comparison cohorts, sequencing platforms, and analytical pipelines, requiring the authors to conduct a qualitative evaluation. The authors concluded that while methodological diversity and limited validation currently constrain the interpretation of individual transcriptomic markers, combining bulk, single-cell, and long-read sequencing provides complementary insights into disease pathogenesis, with future progress dependent on standardised protocols, longitudinal study designs, and multi-tissue integration.

Subject of Research: RNA sequencing studies in diabetic kidney disease

Article Title: Transcriptomic insights into diabetic kidney disease: a systematic review of RNA sequencing studies

Article References: Deb, A., Abdelrahman, Z., Hill, C., Smyth, L., Thakkinstian, A., Meng, W., Sandholm, N., Cole, J. B., Nair, V., Brennan, E., Andrews, D., Giardini, E., Haukka, J. K., Ha, E., Syreeni, A., Dahlström, E. H., Salem, R. M., Fermin, D., Mercader, J. M., … McKay, G. J. (2026). Transcriptomic insights into diabetic kidney disease: a systematic review of RNA sequencing studies. BMC Nephrology. https://doi.org/10.1186/s12882-026-05477-w

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DOI: 10.1186/s12882-026-05477-w

Keywords: diabetic kidney disease, RNA sequencing, transcriptomics, systematic review, kidney biopsy, gene expression, fibrosis, mitochondrial dysfunction, Transcriptomic, insights, diabetic, kidney