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Abstract: TH-PO786

Multidimensional Characterization of Renal Biopsies Integrating Podocyte Morphology with Clinical and Histopathological Features

Session Information

Category: Glomerular Diseases

  • 1403 Podocyte Biology

Authors

  • Pospiech, Johannes, Evotec International GmbH, Gottingen, Niedersachsen, Germany
  • Bohnenpoll, Tobias, Evotec International GmbH, Gottingen, Niedersachsen, Germany
  • Skroblin, Philipp, Evotec International GmbH, Gottingen, Niedersachsen, Germany
  • Endlich, Tim, NIPOKA GmbH, Greifswald, Mecklenburg-Vorpommern, Germany
  • Radresa, Olivier, Evotec International GmbH, Gottingen, Niedersachsen, Germany
  • Endlich, Nicole, NIPOKA GmbH, Greifswald, Mecklenburg-Vorpommern, Germany
  • Andag, Uwe, Evotec International GmbH, Gottingen, Niedersachsen, Germany
Background

Podocyte foot process effacement and loss of glomerular filtration slits are common pathological changes observed in many chronic kidney diseases (CKD). Accurate measurement of podocyte morphology requires electron microscopy or advanced super-resolution light microscopy. Here, we used three-dimensional-structured illumination microscopy (3D-SIM) to quantify glomerular filtration slits in residual diagnostic biopsies of the NURTuRE CKD cohort. We integrated this measure of podocyte foot process morphology with other clinical and histopathological features to enable future precision diagnostics and patient stratification strategies.

Methods

Histological sections of formalin-fixed, paraffin-embedded kidney biopsies were stained for podocin and nephrin and analyzed using the 3D-SIM Podocyte Exact Morphology Measurement Procedure (PEMP). Filtration slit densities (FSD) and filtration slit lengths (FSL), which describe the density and extent of the glomerular filtration network, were derived from a median of 17 glomeruli per sample for 69 NURTuRE CKD patients of various etiologies.

Results

Quantification of podocyte morphology revealed different patterns of intra- and intersample variance with distinct, etiology-dependent distributions, likely reflecting common disease mechanisms. While samples from primary glomerular diseases showed a reduced median FSD and FSL with low intrasample variance, samples from secondary glomerular diseases showed high intrasample variance, suggesting distinct patterns of glomerular injury and disease progression. Moreover, podocyte morphology was strongly correlated with urinary protein and albumin creatinine ratios, but independent of other histopathological features, including glomerulosclerosis ratios and interstitial fibrosis and tubular atrophy scores.

Conclusion

Assessment of podocyte morphology in NURTuRE kidney biopsies supports FSD and FSL as independent and precise histopathological estimators of foot process effacement and glomerular integrity, revealing etiology-specific features of disease. Further integration of clinical time series and renal survival data, will uncover the potential of PEMP for kidney precision diagnostics and risk prediction.

Funding

  • Commercial Support – Evotec SE