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Endogenous H2S production deficiencies lead to impaired renal erythropoietin production

Endogenous H2S production deficiencies lead to impaired renal erythropoietin production
Endogenous H2S production deficiencies lead to impaired renal erythropoietin production

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.

1911-6470
E210-E219
Leigh, Jennifer
44afc669-db3e-4b45-994f-9426542e12c6
Juriasingani, Smriti
75e7c324-312c-4bcf-8f17-42e5f2709bbd
Akbari, Masoud
962579a2-83c2-4b9d-8b62-19f25694d083
Shao, Peng
e6942616-7e00-462e-bc38-fcfffecf516f
Saha, Manujendra N
6071acec-5c7b-4d47-becd-ce3d545d5bca
Lobb, Ian
24dcc2e6-11bf-4507-846c-bc10675261f8
Bachtler, Matthias
e84b3d87-6978-48da-be8e-49bcdf1f8ca1
Fernandez, Bernadette
9890aabc-1fe6-4530-a51e-31182e537131
Qian, Zhongming
74dedcdf-c0a2-4c39-9aba-6a5407693bc8
Van Goor, Harry
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Pasch, Andreas
5f5d9b34-4d9e-40a4-9326-fa1cd352717d
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Wang, Rui
757d84d7-7936-4dfd-a461-25243852553e
Sener, Alp
e5692c21-4587-40ba-8955-5952cded07e9
Leigh, Jennifer
44afc669-db3e-4b45-994f-9426542e12c6
Juriasingani, Smriti
75e7c324-312c-4bcf-8f17-42e5f2709bbd
Akbari, Masoud
962579a2-83c2-4b9d-8b62-19f25694d083
Shao, Peng
e6942616-7e00-462e-bc38-fcfffecf516f
Saha, Manujendra N
6071acec-5c7b-4d47-becd-ce3d545d5bca
Lobb, Ian
24dcc2e6-11bf-4507-846c-bc10675261f8
Bachtler, Matthias
e84b3d87-6978-48da-be8e-49bcdf1f8ca1
Fernandez, Bernadette
9890aabc-1fe6-4530-a51e-31182e537131
Qian, Zhongming
74dedcdf-c0a2-4c39-9aba-6a5407693bc8
Van Goor, Harry
6e4f96a5-c749-43b6-a488-6af71f932dc3
Pasch, Andreas
5f5d9b34-4d9e-40a4-9326-fa1cd352717d
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Wang, Rui
757d84d7-7936-4dfd-a461-25243852553e
Sener, Alp
e5692c21-4587-40ba-8955-5952cded07e9

Leigh, Jennifer, Juriasingani, Smriti, Akbari, Masoud, Shao, Peng, Saha, Manujendra N, Lobb, Ian, Bachtler, Matthias, Fernandez, Bernadette, Qian, Zhongming, Van Goor, Harry, Pasch, Andreas, Feelisch, Martin, Wang, Rui and Sener, Alp (2019) Endogenous H2S production deficiencies lead to impaired renal erythropoietin production. Canadian Urological Association Journal, 13 (7), E210-E219. (doi:10.5489/cuaj.5658).

Record type: Article

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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e-pub ahead of print date: 20 November 2018
Published date: July 2019

Identifiers

Local EPrints ID: 430085
URI: http://eprints.soton.ac.uk/id/eprint/430085
ISSN: 1911-6470
PURE UUID: 5eb2383d-1977-4264-98c5-1e28a224f8a7
ORCID for Bernadette Fernandez: ORCID iD orcid.org/0000-0001-6337-0381
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

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Date deposited: 11 Apr 2019 16:30
Last modified: 16 Mar 2024 04:13

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Contributors

Author: Jennifer Leigh
Author: Smriti Juriasingani
Author: Masoud Akbari
Author: Peng Shao
Author: Manujendra N Saha
Author: Ian Lobb
Author: Matthias Bachtler
Author: Bernadette Fernandez ORCID iD
Author: Zhongming Qian
Author: Harry Van Goor
Author: Andreas Pasch
Author: Martin Feelisch ORCID iD
Author: Rui Wang
Author: Alp Sener

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