Endogenous H2S production deficiencies lead to impaired renal erythropoietin production

Authors

  • Jennifer Leigh Department of Microbiology and Immunology, Western University
  • Smriti Juriasingani
  • Masoud Akbari Matthew Mailing Center for Translational Transplant Studies, London Health Sciences Centre http://orcid.org/0000-0003-2315-7302
  • Peng Shao Department of Physiology, Western University
  • Manujendra N. Saha Matthew Mailing Center for Translational Transplant Studies, London Health Sciences Centre
  • Ian Lobb Department of Microbiology and Immunology, Western University
  • Matthias Bachtler Department of Clinical Research, University of Bern, Bern, Switzerland
  • Bernadette Fernandez Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, United Kingdom
  • Zhongming Qian Laboratory of Neuropharmacology, Fudan University School of Pharmacy, Shanghai, China.
  • Harry van Goor Department of Pathology and Medical Biology, University of Groningen
  • Andreas Pasch Department of Clinical Chemistry, University Hospital Bern (Inselspital), Bern, Switzerland
  • Martin Feelisch Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, United Kingdom
  • Rui Wang The Cardiovascular and Metabolic Research Unit, Laurentian University, Sudbury, Ontario, Canada
  • Alp Sener

DOI:

https://doi.org/10.5489/cuaj.5658

Keywords:

chronic kidney disease, renal erythropoietin deficiency, hydrogen sulfide

Abstract

Introduction: Patients suffering from chronic kidney disease (CKD) experience a number of associated comorbidities, including anemia. Relative deficiency in renal erythropoietin (EPO) production is thought to be a primary cause of anemia. Interestingly, CKD patients display low levels of hydrogen sulfide (H2S), an endogenously derived renal oxygen sensor. Previous in vitro experiments have revealed that H2S-deficient renal cell lines produce less EPO than wild-type renal cell lines during hypoxia.

Methods: We postulated that H2S might be a primary mediator of EPO synthesis during hypoxia, which was tested using an in vivo murine model of whole-body hypoxia and in clinical samples obtained from CKD patients.

Results: Following a 72-hour period of hypoxia (11% O2), partial H2S knockout mice (lacking the H2S biosynthetic enzyme cystathionine γ-lyase [CSE]) displayed lower levels of hemoglobin, EPO, and cystathionine-β-synthase (CBS) (another H2S biosynthetic enzyme) compared to wild-type mice, all of which was rescued by exogenous H2S supplementation. We also found that anemic CKD patients requiring exogenous EPO exhibited lower urinary thiosulfate levels compared to non-anemic CKD patients of similar CKD classification.

Conclusions: Together, our results confirm an interplay between the actions of H2S during hypoxia and EPO production.

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Published

2018-11-20

How to Cite

Leigh, J., Juriasingani, S., Akbari, M., Shao, P., Saha, M. N., Lobb, I., … Sener, A. (2018). Endogenous H2S production deficiencies lead to impaired renal erythropoietin production. Canadian Urological Association Journal, 13(7). https://doi.org/10.5489/cuaj.5658

Issue

Vol. 13 No. 7 (2019): CUAJ July

Section

Original Research

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