Kidney Week

Abstract: TH-PO578

Ex Vivo Kidney Perfusion as a Model for Recurrent Focal Segmental Glomerulosclerosis

Session Information

• Glomerular Diseases: Omics, Biomarkers, and Tools
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

• Muehlig, Anne Katrin, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Germany

Anne Katrin Muehlig, MD

• Braun, Fabian, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Germany

Fabian Braun, MD

• Rischke, Paula Franziska, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany

Paula Franziska Rischke

• Oh, Jun, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany

Jun Oh, MD

• Haenzelmann, Sonja, Universitatsklinikum Hamburg-Eppendorf Zentrum fur Molekulare Neurobiologie Hamburg, Hamburg, Hamburg, Germany

Sonja Haenzelmann, PhD

• Poets, Manuela, Universitatsklinikum Hamburg-Eppendorf Zentrum fur Molekulare Neurobiologie Hamburg, Hamburg, Hamburg, Germany

Manuela Poets

• Wingerath, Madelaine, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany

Madelaine Wingerath

• Homeyer, Inka Christina, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany

Inka Christina Homeyer

• Kretz, Oliver, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Germany

Oliver Kretz, MD, DrMed, MBA

• Puelles, Victor G., Universitatsklinikum Hamburg-Eppendorf, Hamburg, Germany

Victor G. Puelles, MD, PhD

• Czogalla, Jan, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Germany

Jan Czogalla, MD

• Huber, Tobias B., Universitatsklinikum Hamburg-Eppendorf, Hamburg, Germany

Tobias B. Huber, MD, FASN

Background

Primary focal segmental glomerulosclerosis (FSGS) recurs in about 40%, indicative of a yet unidentified circulating factor. Recently, we detected several novel pathways in an in vitro model of podocytes incubated with recurrent (r)FSGS patient sera. To characterize their importance under conditions of intact glomerular integrity, we used ex vivo perfusion of mouse kidneys with plasma from rFSGS-patients.

Methods

Kidneys of transgenic podocyte-reporter mice were perfused with plasma from 5 different rFSGS patients and 3 controls (fig 1) (n=20). The glomerular physiology, ultrastructure, protein- and mRNA expression were analyzed using urinanalysis, immunofluorescence, electron microscopy and mRNA bulk sequencing of isolated glomeruli.

Results

Perfusion with rFSGS plasma resulted in an impairment of the filtration barrier, foot process effacement, downregulation of the podocyte marker synaptopodin, remodeling of podocytes and detection of human albumin in the urine of perfused kidneys. mRNA bulk sequencing of glomeruli revealed 802 differentially regulated genes. In rFSGS plasma perfused kidneys integrin b1 and fibronectin were both strongly regulated in the same direction as in rFSGS serum-incubated podocytes in our previous experiments.

Conclusion

Ex vivo perfusion with rFSGS plasma resulted in a disruption of the glomerular filtration barrier and was able to recapitulate our previous in vitro findings. This study validates ex vivo perfusion of mouse kidneys with human plasma as a model to study rFSGS in the intact cellular architecture. This model represents a valuable tool to identify and target new FSGS pathomechanisms.

Isolated perfused mouse kidneys (A) and perfusion set up (B)