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Updated: Aug 27, 2025

Identification of the Source of Secreted Proteins in the Kidney by Brefeldin A Injection
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Identification of the Source of Secreted Proteins in the Kidney by Brefeldin A Injection

Published on: November 10, 2021

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A PHD inhibitor prevents changes in the phosphoproteome and capillary rarefaction by CsA: treatment option for CKD?

Gunnar Schley1, Margarete Goppelt-Struebe1

  • 1Department of Nephrology and Hypertension, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

Kidney International
|September 23, 2022
PubMed

Insights

Cyclosporine A causes kidney damage by altering blood vessel proteins and reducing capillaries. Daprodustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, may protect kidney microvasculature from this damage.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Pharmacology

Background:

  • Chronic cyclosporine A administration leads to nephrotoxicity.
  • Kidney damage is often associated with impaired microvasculature and reduced hemoglobin.
  • Angiogenic pathways are significantly altered in chronic kidney disease.

Purpose of the Study:

  • To investigate the phosphoproteomic changes in a mouse model of chronic cyclosporine A nephrotoxicity.
  • To evaluate the therapeutic potential of hypoxia-inducible factor prolyl hydroxylase inhibitors in preventing cyclosporine A-induced kidney damage.

Main Methods:

  • Analysis of the phosphoproteome in kidney tissue from a mouse model.
  • Assessment of hemoglobin levels and kidney capillary density.
  • Coadministration of daprodustat with cyclosporine A.

Main Results:

  • Significant alterations in the angiogenic pathway were detected in the phosphoproteome.
  • Reduced hemoglobin levels and capillary rarefaction were observed in the kidney.
  • Daprodustat treatment largely prevented phosphoproteomic changes and capillary rarefaction.

Conclusions:

  • Prolyl hydroxylase domain enzyme inhibitors, such as daprodustat, may preserve kidney microvasculature.
  • Targeting angiogenic pathways could be a therapeutic strategy for chronic kidney disease.
  • Daprodustat shows promise in mitigating cyclosporine A-induced nephrotoxicity.

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