Endogenous H2S production deficiencies lead to impaired renal erythropoietin production

  • 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
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.

Published
2018-11-20
How to Cite
Leigh, J., Juriasingani, S., Akbari, M., Shao, P., Saha, M. N., Lobb, I., Bachtler, M., Fernandez, B., Qian, Z., van Goor, H., Pasch, A., Feelisch, M., Wang, R., & 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
Section
Original Research