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Soluble Fas affects erythropoiesis in vitro and acts as a potential predictor of erythropoiesis-stimulating agent therapy in patients with chronic kidney disease.

  • Chiloff, Daniela Mendes1
  • de Almeida, Danilo Candido1
  • Dalboni, Maria A1
  • Canziani, Maria Eugênia1
  • George, Sunil K2
  • Morsi, Alshaimaa Mahmoud2
  • El-Akabawy, Nadia2, 3
  • Porada, Christopher D2
  • Durao, Marcelino Souza1
  • Zarjou, Abolfazl4
  • Almeida-Porada, Graca2
  • Goes, Miguel Angelo1, 2
  • 1 Nephrology Division, Federal University of São Paulo, São Paulo, Brazil. , (Brazil)
  • 2 Wake Forest Institute for Regenerative Medicine, Winston Salem, North Carolina.
  • 3 Zagazig University, Zagazig, Egypt. , (Egypt)
  • 4 University of Alabama at Birmingham, Birmingham, Alabama.
Published Article
AJP Renal Physiology
American Physiological Society
Publication Date
Apr 01, 2020
DOI: 10.1152/ajprenal.00433.2019
PMID: 32003597


Serum soluble Fas (sFas) levels are associated with erythropoietin (Epo) hyporesponsiveness in patients with chronic kidney disease (CKD). Whether sFas could predict the need for erythropoiesis-stimulating agent (ESA) usage and its influence in erythropoiesis remain unclear. We evaluated the relation between sFas and ESA therapy in patients with CKD with anemia and its effect on erythropoiesis in vitro. First, we performed a retrospective cohort study with 77 anemic patients with nondialysis CKD. We performed in vitro experiments to investigate whether sFas could interfere with the behavior of hematopoietic stem cells (HSCs). HSCs were isolated from umbilical cord blood and incubated with recombinant sFas protein in a dose-dependent manner. Serum sFas positively correlated with Epo levels (r = 0.30, P = 0.001) but negatively with hemoglobin (r = -0.55, P < 0.001) and glomerular filtration rate (r = -0.58, P < 0.001) in patients with CKD at baseline. Elevated sFas serum levels (4,316 ± 897 vs. 2,776 ± 749, P < 0.001) with lower estimated glomerular filtration rate (26.2 ± 10.1 vs. 33.5 ± 14.3, P = 0.01) and reduced hemoglobin concentration (11.1 ± 0.9 vs. 12.5 ± 1.2, P < 0.001) were identified in patients who required ESA therapy compared with patients with non-ESA. Afterward, we detected that the sFas level was slight correlated with a necessity of ESA therapy in patients with nondialysis CKD and anemia. In vitro assays demonstrated that the erythroid progenitor cell frequency negatively correlated with sFas concentration (r = -0.72, P < 0.001). There was decreased erythroid colony formation in vitro when CD34+ HSCs were incubated with a higher concentration of sFas protein (1.56 ± 0.29, 4.33 ± 0.53, P < 0.001). Our findings suggest that sFas is a potential predictor for ESA therapy in patients with nondialysis CKD and that elevated sFas could affect erythropoiesis in vitro.

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