RESUMO
BACKGROUND: Anemia is common in chronic kidney disease (CKD) and is associated with outcomes. In addition, serum soluble Fas (sFas) levels are related to anemia and erythropoietin (EPO) resistance. OBJECTIVES: Firstly, to compare clinical data and serum levels of sFas, EPO, and pro-inflammatory markers between patients with non-dialytic CKD (NDD-CKD) and healthy subjects. Subsequently, to compare and evaluate the relationship of serum EPO, sFas levels with anemia, and outcomes in patients with NDD-CKD over a long follow-up period. METHODS: We performed a retrospective study in 58 NDD-CKD patients compared with 20 healthy subjects on complete blood count, kidney function, serum EPO, sFas, and inflammatory markers (CRP, IL- 6, and IFN-γ) at baseline. We then compared the same baseline data between patients with NDD-CKD who evolved to anemia and those who did not have anemia over the follow-up. We also evaluated the frequency of outcomes in patients with CKD with higher sFas levels. Finally, we performed a multivariate analysis of factors associated with CKD anemia. RESULTS: There were lower eGFR and Hb but higher serum inflammatory markers, sFas levels, sFas/eGFR, and EPO/Hb ratios in patients with NDD-CKD. Comparatively, on the other hand, NDD-CKD patients with anemia had lower eGFR but were older, had more diabetes, and had higher sFas/ eGFR, EPO/Hb ratios, and serum levels of IL-6 and sFas than NDD-CKD without anemia for an extended period. In addition, there was an association in a multivariate analysis of diabetes, age, and sFas levels with kidney anemia. Furthermore, there were higher frequencies of outcomes in increased serum sFas levels. CONCLUSION: As an elective risk factor, serum sFas levels, in addition to age and diabetes, were independently associated with kidney anemia for an extended period. Thus, more studies are necessary to analyze the proper relationship of sFas with kidney anemia and its outcomes and therapy in CKD.
Assuntos
Anemia , Insuficiência Renal Crônica , Humanos , Estudos Retrospectivos , Insuficiência Renal Crônica/complicações , Anemia/complicações , Voluntários Saudáveis , Análise MultivariadaRESUMO
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.