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Kidney Week

ASN / Education & Meetings / Kidney Week /
Abstract: FR-PO959

Fewer Podocytes Associate with Progressive CKD Independent of Glomerular Volume and Nephrosclerosis or Clinical Characteristics

Session Information

Category: Pathology and Lab Medicine

  • 1800 Pathology and Lab Medicine

Authors

  • Denic, Aleksandar, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Kumar, Mahesh, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Aperna, Fnu, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Shaik, Afsana Ansari, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Mullan, Aidan F., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Alexander, Mariam P., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Hodgin, Jeffrey B., University of Michigan, Ann Arbor, Michigan, United States
  • Rule, Andrew D., Mayo Clinic Minnesota, Rochester, Minnesota, United States
Background

Per podometric hypothesis, podocyte loss leads to glomerulosclerosis and proteinuria, eventually leading to chronic kidney disease (CKD). Podometrics include the podocyte density, volume, and number per glomerulus. Prior studies investigated podometrics in kidney donors, autopsy kidneys or patients with specific kidney diseases such as IgA nephropathy. The goal of this study is to investigate associations between podometrics and progressive CKD in patients with radical nephrectomy.

Methods

We evaluated the WT1 (stains podocyte nuclei) and Glepp1 (stains podocyte cytoplasm) wedge sections of renal parenchyma from radical nephrectomies due to kidney tumor performed between 2000 and 2021. QuPath software was used to quantify number of WT-1 positive cells and Glepp-1 positive area within a glomerular tuft. Progressive CKD was defined as dialysis, kidney transplantation, sustained eGFR <10 ml/min per 1.73m2 or sustained 30% eGFR decline from the post-nephrectomy eGFR during follow-up to March 2024. Each case of progressive CKD was age-sex-matched to 1 control without progressive CKD. Logistic regression models assessed the risk of progressive CKD with podometric measures adjusting for glomerular volume, nephrosclerosis and clinical characteristics (age, sex, body mass index, diabetes, hypertension, baseline eGFR, and 24 hour urine protein).

Results

There were 35 cases and 35 controls. Compared to cases, controls had higher podocyte density (207 vs. 158 per 106 μm3, p=0.004), higher podocyte number per glomerulus (503 vs. 422, p=0.01), but smaller total podocyte cell volume (3,286 vs. 3,868 μm3, p=0.047). Lower podocyte density and larger podocyte cell volume associated with hypertension. Lower podocyte density and lower podocyte number per glomerulus associated with progressive CKD (Table).

Conclusion

Fewer podocytes in glomeruli are strongly associated with progressive CKD independent of established clinical and histological prognostic factors for CKD.

Per SDUnadjustedAdjusted for glomerular volume and nephrosclerosisAdjusted for clinical characteristics
OR (95% CI)POR (95% CI)POR (95% CI)P
Podocyte density, per μm30.46 (0.25-0.78)0.0070.33 (0.11-0.81)0.030.38 (0.18-0.74)0.007
Podocyte number per glomerulus0.49 (0.25-0.84)0.020.48 (0.23-0.87)0.030.40 (0.19-0.74)0.007
Podocyte volume1.71 (1.02-3.23)0.061.75 (0.72-5.15)0.241.70 (0.87-3.75)0.15

Funding

  • NIDDK Support