Kidney Week

Abstract: TH-PO0337

Podocytic Injury Alters Circadian Gene Expression in the Kidney Glomeruli

Session Information

• Glomerular Diseases: Omics
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

• Lemberg, Katharina, Universitatsklinikum Koln, Cologne, NRW, Germany

Katharina Lemberg, MD

• Chen, He, Universitatsklinikum Koln, Cologne, NRW, Germany

He Chen, PhD

• Padvitski, Tsimafei, Universitat zu Koln, Cologne, NRW, Germany

Tsimafei Padvitski, MS

• Papadakis, Antonios, Exzellenzcluster CECAD in der Universitat zu Koln, Cologne, NRW, Germany

Antonios Papadakis, MSc, PhD

• Nüßing, Elisa, Universitat zu Koln, Cologne, NRW, Germany

Elisa Nüßing

• Benzing, Thomas, Universitatsklinikum Koln, Cologne, NRW, Germany

Thomas Benzing, MD, PhD, FASN

• Schermer, Bernhard, Universitatsklinikum Koln, Cologne, NRW, Germany

Bernhard Schermer, MD

• Beyer, Andreas, Universitat zu Koln, Cologne, NRW, Germany

Andreas Beyer, PhD

• Kann, Martin, Universitatsklinikum Koln, Cologne, NRW, Germany

Martin Kann, MD

Group or Team Name

• Nephrolab, Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne and University Hospital Cologne

Background

Key aspects of renal physiology are regulated by the circadian clock, including glomerular filtration rate, tubular transport, and electrolyte homeostasis. Recent studies in murine models have demonstrated that disruption of the circadian clock in podocytes leads to proteinuria and electrolyte disturbances. However, whether podocyte injury conversely disrupts circadian rhythmicity remains poorly understood. To better elucidate the reciprocal relationship between the two, we investigated whether podocyte injury feeds back on circadian regulation.

Methods

We used the well-established compound-heterozygous podocin mutant mouse model of nephrotic syndrome (Nphs2^R231Q/A286V) and analyzed glomerular circadian gene expression in diseased and control mice at 4-hour intervals over a 24-hour time period using bulk RNA sequencing. For circadian analysis, we applied the R package "GLMMcosinor".

Results

Bulk RNA sequencing of glomeruli from control and podocin mutant mice at six circadian time points revealed a marked expansion of rhythmically expressed genes, increasing from 2,850 (15.6%) in controls to 7,352 (40.3%) in diseased mice. Expression of core circadian transcription factors was largely altered, with NR1D1 showing the most pronounced deviation in amplitude and acrophase. The bimodal acrophase distribution seen in controls was disrupted in podocin-mutant mice, where the early peak was diminished, and the late peak was delayed by 2-4 hours. Gene ontology analysis revealed that rhythmically expressed genes unique to podocin mutant mice were enriched in pathways related to vascular remodeling, tissue morphogenesis, and hormonal signaling. Notably, KEGG analysis further identified PI3K/AKT, MAPK, Ras, and Rap1 signaling pathways as significantly enriched exclusively in podocin mutant mice.

Conclusion

In summary, our findings demonstrate that podocyte injury profoundly disrupts glomerular circadian gene expression in podocin mutant mice. Rhythmic expression of genes involved in vascular remodeling, tissue morphogenesis, and hormonal signaling emerged specifically in podocin-mutant mice, pointing to a reorganization of circadian transcriptional programs in nephrotic syndrome. Whether these changes actively contribute to disease progression warrants further investigation.

Acknowledgment

Declaration of AI tools
We acknowledge the use of Claude (Anthropic, Sonnet 4.6), an AI language model, for assistance in statistical modeling and visualization, using R code. The model was used to generate and debug code; all outputs were reviewed, tested, and adapted by the authors to ensure correctness.

Funding

• Government Support – Non-U.S.