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Abstract: SA-PO1023

The Decrease of the Filtration Slit Density, Not Proteinuria, Is the Early Indication of Filtration Barrier Dysfunction

Session Information

Category: Glomerular Diseases

  • 1403 Podocyte Biology

Authors

  • Endlich, Nicole, NIPOKA GmbH, Germany, Germany
  • Chadjichristos, Christos E., INSERM UMR S 1155, Hôpital Tenon, Paris, France
  • Chatziantoniou, Christos, INSERM UMR S 1155, Hôpital Tenon, Paris, France
  • Telli, Nihal, NIPOKA GmbH, Germany, Germany
  • Drenic, Vedran, NIPOKA GmbH, Germany, Germany
  • Endlich, Tim, NIPOKA GmbH, Germany, Germany
Background

Intact podocyte foot processes (FP) are essential for a proper slize selective filtration. Changes in FP morphology are thought to be the first event leading to proteinuria, but this has yet to be proven. Since FP are below the optical resolution of a light microscope, changes are studied on ultrathin sections by electron microscopy. Here, we show the relationship between morphology and proteinuria using podocyte exact morphology measurement procedure (PEMP), which is a 3D-SIM-based procedure.

Methods

Mice were treated with NTS and sacrificed 24, 48, and 72 h after injection. 3D-SIM was done on podocin and integrin co-stained standard formalin-fixed and paraffin-embedded kidney sections (3 µm). The filtration slit density (FSD) was measured by PEMP (Siegerist, 2017). Electron microscopic analysis were done on glutaraldehyde fixed tissue and processed using standard procedures. Albumin to creatine ratios were also analyzed.

Results

We have found, that mice developed moderate proteinuria 48 h after NTS injection. Using PEMP, we found that the FSD was already significantly reduced in NTS-treated mice at 24 h compared to control-injected mice. Transmission electron microscopy analysis confirmed the presence of these structural alterations, indicating that effacement of the podocytes serves as the initial indication, followed by the onset of proteinuria.

Conclusion

PEMP analysis of standard histological sections from NTS-injected and control mice demonstrated that the first event in the functional loss of the size selectivity of the filtration barrier is the effacement of FP morphology, followed by detectable proteinuria. Therefore, the assessment of the FSD is a promising strategy for early and accurate detection of a loss of filtration barrier integrity, providing opportunities for faster and precise diagnostics.

Funding

  • Commercial Support – NIPOKA GmbH