| First Author | Leigh J | Year | 2018 |
| Journal | Can Urol Assoc J | Pages | E210-E219 |
| PubMed ID | 30472982 | Mgi Jnum | J:288187 |
| Mgi Id | MGI:6430933 | Doi | 10.5489/cuaj.5658 |
| Citation | Leigh J, et al. (2018) Endogenous H2S production deficiencies lead to impaired renal erythropoietin production. Can Urol Assoc J :E210-E219 |
| abstractText | 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 gamma-lyase [CSE]) displayed lower levels of hemoglobin, EPO and cystathionine-beta-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. |
