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Kidney Week

Abstract: TH-PO1071

Long-Term Risk of CKD After Kidney Donation Is Higher with More Podocytes per Glomerulus

Session Information

Category: Pathology and Lab Medicine

  • 1700 Pathology and Lab Medicine

Authors

  • Vitoriano, Jessica Eleuterio, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Denic, Aleksandar, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Fareeduddin, Syed Khooshal, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Mullan, Aidan F., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Barisoni, Laura, Duke University, Durham, North Carolina, United States
  • Shankland, Stuart J., University of Washington, Seattle, Washington, United States
  • Rule, Andrew D., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States

Group or Team Name

  • Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN
Background

Podocyte metrics are linked to chronic kidney disease (CKD) progression in certain conditions, however data in healthy individuals are lacking. Using living kidney donors as a model, we evaluated whether baseline podometric measures at donation predict CKD.

Methods

Case-control study of living kidney donors from the Aging Kidney Anatomy Study (2000 to 2023) with protocol biopsy at donation. Cases that developed post-donation CKD (eGFR<45 ml/min/1.73m2) were matched to controls with preserved eGFR (≥45 mL/min/1.73m2) by age, sex, and follow-up time. Immunohistochemistry (WT1, GLEPP1, PAX8), morphometry (QuPath), and stereological models quantified podocyte and parietal epithelial cell (PEC) measures. Conditional logistic regression assessed risk of CKD with podometric measures.

Results

Forty cases and 40 matched controls (mean follow-up eGFR was 11–12 years after donation) were analyzed. Cases had lower baseline eGFR, larger glomerular tuft volumes, and more interstitial fibrosis/tubular atrophy. Larger glomerular volume correlated with higher podocyte number (rs=0.30, p=0.006) and lower podocyte density (rs=−0.46, p<0.0001). Among podometric measures, higher podocyte number per glomerulus associated with developing post-donation CKD, but not after adjustment for glomerular volume. After glomerular volume adjustment, lower PEC number per glomerulus associated with developing post-donation CKD.

Conclusion

These results indicate that podocyte numbers may rise as a compensatory response to glomerular hypertrophy and hyperfiltration in healthy adults with normal kidney function. The PECs may serve as a reservoir for the increase in podocyte number with glomerular hypertrophy.

Figure 1. Example of immunohistochemistry staining for (A) podocyte nuclei (WT1), and in an adjacent section of the same glomerulus stained for (B) parietal epithelial cells (PAX8).

Funding

  • NIDDK Support