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ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

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Kidney Week

Abstract: PO1606

Systems Analyses of Renal Fabry Transcriptome and Response to Enzyme Replacement Therapy (ERT) Identifies a Cross-Validated and Druggable ERT-Resistant Module

Session Information

Category: Genetic Diseases of the Kidneys

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic


  • Eikrem, Oystein, University of Bergen, Bergen, Norway
  • Delaleu, Nicolas, 2C SysBioMed, Contra, Switzerland
  • Strauss, Philipp, University of Bergen, Bergen, Norway
  • Sekulic, Miroslav, UH Cleveland Medical Center, Cleveland, Ohio, United States
  • Tøndel, Camilla, Haukeland University Hospital, Bergen, Norway
  • Leh, Sabine, Haukeland University Hospital, Bergen, Norway
  • Svarstad, Einar, University of Bergen, Bergen, Norway
  • Skrunes, Rannveig, Haukeland University Hospital, Bergen, Norway
  • Nowak, Albina, University Hospital of Zurich, Zurich, Switzerland
  • Rusu, Elena-Emanuela, Fundeni Clinical Institute, Bucharest, Romania
  • Osman, Tarig Al-Hadi, University of Bergen, Bergen, Norway
  • Marti, Hans-Peter, University of Bergen, Bergen, Norway

Group or Team Name

  • Renal Research Group Bergen

Fabry nephropathy (FN) is caused by mutations in the α-galactosidase A gene and can be managed with ERT. Via understanding the molecular basis of FN and long-term ERT impact, we aim at a framework for selection of biomarkers/drug-targets.


Obtained from normal controls and two independent FN-cohorts, mRNA-isolates from archival kidney biopsies (n=41) taken prior and up to 10 years of ERT were subjected to RNAseq and partly IHC. Combining pathway-centered analyses with network-science allowed computation of transcriptional landscapes from glomeruli, proximal/distal tubuli & arteries and integration with existing proteome and drug::target data.


Despite inter-cohort heterogeneity, FN seemed well controlled, esp. via early introduced ERT. Pathways consistently altered in both FN-cohorts pre-ERT vs. controls were limited to glomeruli and arteries and commonly pertained to same biological themes. While glomerular keratinization-related processes were ERT sensitive, a majority of alterations, such as transporter activity and responses to stimuli, remained dysregulated or remerged despite ERT. Inferring an ERT-resistant genetic module on this basis identified targets suitable for drug repurposing (Figure 1).


Transcriptional landscapes of kidney compartments reflected differences in FN-cohorts. ERT can revert FN molecular state to closely match controls. We identified and cross-validated ERT-resistant modules, when leveraged with external data, allowed estimating their suitability as biomarkers and targets for adjunct treatment.

Figure 1. Target::Target::Drug interactome. Node color target: green=glomerular target, blue=arterial target.


  • Government Support - Non-U.S.