Date: Tuesday, June 14, 2016
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Halls C&D
Anemia affects 90% of hemodialysis patients and is a tremendous concern for patients and health care providers. CKD leads to chronic interstitial fibrosis which leads to a dysfunction in the kidneys' ability to secrete erythropoietin (EPO), despite the persistent renal hypoxia present in chronic kidney disease (CKD), thus necessitating the use of exogenous EPO preparations in many anemic patients. Additionally, these patients have been found to possess low levels of hydrogen sulfide (H2S), a recently discovered endogenously derived renal oxygen sensor molecule. Given this, we postulated that H2S may be the primary mediator of EPO production during hypoxia, which was tested using both in vivo and clinical patient samples. We found that following a 72 h period of 11% hypoxia , CSE -/- mice (deficient in the enzyme responsible for H2S production), showed significantly lower levels of hemoglobin, EPO and other HIF regulated genes, all of which were subsequently rescued by exogenous H2S supplementation. This was opposite in wild type mice. This phenomenon was also found to translate to the clinical setting where urinary H2S levels in CKD patients suffering anemia requiring exogenous EPO supplementation exhibited significantly lower urinary H2S and thiosulfate levels compared to CKD patients who weren't anemic (Figure 1). Urinary nitrate and nitrite levels measured by HPLC also didn't differ between the two groups, indicating that H2S is responsible for the deficient EPO production rather than nitric oxide as once previously reported. Together, these data suggest a previously undocumented interplay between the production and actions of H2S during hypoxia and subsequent EPO production, allowing for the potential use of newly developed H2S donor molecules as a novel therapeutic strategy in treating patients with anemia of CKD.
CITATION INFORMATION: Leigh J, Shao P, Saha M, Lobb I, Pasch A, van Goor H, Feelisch M, Wang R, Sener A. Hydrogen Sulphide Is an Important Regulator of Erythropoietin Synthesis in Patients with Anemia of Chronic Kidney Disease. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:Leigh J, Shao P, Saha M, Lobb I, Pasch A, Goor Hvan, Feelisch M, Wang R, Sener A. Hydrogen Sulphide Is an Important Regulator of Erythropoietin Synthesis in Patients with Anemia of Chronic Kidney Disease. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/hydrogen-sulphide-is-an-important-regulator-of-erythropoietin-synthesis-in-patients-with-anemia-of-chronic-kidney-disease/. Accessed June 4, 2020.
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