Hepcidin and diabetes are independently related with soluble transferrin receptor levels in chronic dialysis patients

Ren Fail. 2019 Nov;41(1):662-672. doi: 10.1080/0886022X.2019.1635893.

Abstract

Background: Soluble transferrin receptor (sTfR) is a biomarker of erythropoiesis, which is often impaired in dialysis patients. The aim of our study was to evaluate sTfR levels in chronically dialyzed patients and assess potential determinants of its levels. Methods: We performed a cross-sectional study by evaluating 246 end-stage renal disease patients undergoing dialysis and 32 healthy controls. Circulating levels of interleukin (IL)-6, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, hepcidin, sTfR, growth differentiation factor 15 (GDF15), and traditional iron metabolism markers were measured, as well as hemogram parameters. Clinical data was obtained from all patients. Results: Compared to controls, patients presented similar values of sTfR, reticulocytes and reticulocyte production index (RPI), and significantly higher levels of IL-6, CRP, ferritin, hepcidin, TNF-α, and GDF15. Iron, transferrin, hemoglobin levels, erythrocyte count, mean cell hemoglobin (MCH), and mean cell hemoglobin concentration (MCHC) values were significantly lower in dialysis group. Within patients, sTfR values were higher in diabetic patients and were positively and significantly correlated with reticulocytes and erythrocytes, RPI, and therapeutic doses of erythropoiesis stimulating agents (ESA) and intravenous iron; and inversely and significantly correlated with circulating iron, ferritin, transferrin saturation, hepcidin, MCH, and MCHC. In multiple linear regression analysis, ESA dose, RPI, serum iron, diabetes, and hepcidin levels were independently associated with sTfR levels in dialysis patients and, thus, with erythropoiesis. Conclusion: Our data suggest that, besides RPI and ESA dose, diabetes and hepcidin are closely related to erythropoiesis in dialysis patients. The influence of diabetes on sTfR levels deserves further investigation.

Keywords: End-stage renal disease; erythropoiesis; hepcidin; iron; soluble transferrin receptor.

MeSH terms

  • Aged
  • Anemia, Iron-Deficiency / blood*
  • Anemia, Iron-Deficiency / therapy
  • Biomarkers / blood
  • Case-Control Studies
  • Cross-Sectional Studies
  • Diabetes Mellitus / epidemiology*
  • Erythropoiesis / physiology
  • Erythropoietin / therapeutic use
  • Female
  • Hematinics / administration & dosage
  • Hepcidins / blood*
  • Humans
  • Iron / blood
  • Kidney Failure, Chronic / blood*
  • Kidney Failure, Chronic / therapy
  • Male
  • Middle Aged
  • Receptors, Transferrin / blood*
  • Renal Dialysis*
  • Transferrin / analysis

Substances

  • Biomarkers
  • Hematinics
  • Hepcidins
  • Receptors, Transferrin
  • Transferrin
  • Erythropoietin
  • Iron

Grants and funding

This work was supported by the Applied Molecular Biosciences Unit (UCIBIO), which is financed by national funds from FCT/MCTES [UID/MULTI/04378/2019] and North Portugal Regional Coordination and Development Commission [CCDR-N]/NORTE2020/Portugal 2020 [Norte-01–0145-FEDER-000024].