New parameters in iron metabolism and functional iron deficiency in patients on maintenance hemodialysis

Abstract

INTROduCTION Iron metabolism has been studied for many years. New substances involved in iron metabolism continue to be described. Functional iron deficiency (FID) is characterized by the presence of adequate iron stores (as defined by standard criteria) but insufficient iron mobilization required for erythropoiesis during administration of erythropoiesis-stimulating agents. ObjECTIvEs The aim of the study was to evaluate new parameters of iron metabolism and the prevalence of FID as well as to assess potential correlations in patients on hemodialysis (HD). PATIENTs ANd mEThOds The study included 98 patients on maintenance HD. Standard laboratory methods were used to measure the iron status, complete blood count, creatinine, calcium, phosphorus, albumin, intact parathyroid hormone, and lipids. Commercially available kits were used to measure high-sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6), tumor necrosis factor-α, N-terminal pro-B-type natriuretic peptide (NT-proBNP), growth differentiation factor (GDF15), bone morphogenetic protein (BMP6), hemojuvelin, and hepcidin. REsuLTs FID was present in 23% of the patients on HD and was associated with significantly higher serum ferritin, IL-6, hsCRP, hepcidin, and NT-proBNP levels. There were no significant differences in BMP6 and GDF15 levels between patients with and without FID. Patients on HD had increased prevalence of hypertension, diabetes, and left ventricular hypertrophy and required slightly, but insignificantly, higher erythropoietin doses. Predictors of FID included serum iron levels and residual renal function. CONCLusIONs FID is present in a substantial proportion of patients on HD, who thus should be screened for reversible causes of inflammation. New parameters in iron metabolism do not seem to be related to FID in patients on HD.

Can Serum Gdf-15 be Associated with Functional Iron Deficiency in Hemodialysis Patients?

“…Thus, when compared to the patients in which the target hemoglobin level is reached and who have sufficient iron stores, the high levels of hepcidin in patients with FID is expected. In some studies, hepcidin levels in HD patients who have FID were high, consistent with the results of the present study [24,25]. We also observed high hepcidin in patients with FID.…”

“…GDF15 might cause FID development by hepcidin-independent or -dependent mechanisms. In a study by Malyszko et al, they found no difference in GDF15 levels in HD patients with or without FID [25]. The most important difference of the current study from that of Malyszko et al is that they defined FID in a different manner in HD patients and the number of patients with FID (n = 23) is quite low in their study.…”

Iron Status and Inflammation in Early Stages of Chronic Kidney Disease

“…The correlation between hepcidin and ferritin was not find in patients with functional iron deficiency probably due to a limited sample size. The difference between functional iron deficiency and normal iron status did not reach, statistical significance, as it was reported previously in dialyzed patients [12], probably due to low number of patients with functional iron deficiency in the population studied with early stages of CKD.…”

“…Previous studies concerned the patients with end stage kidney disease or patients on renal replacement therapy. Malyszko et al [12] revealed that the vast majority of hemodialysis patients presented functional iron deficiency that stemmed from subclinical inflammatory state. Therefore, in hemodialysis patients we should first pursuit to reveal and cure the reversible causes of inflammatory state.…”

Impact of Inflammation on Ferritin, Hepcidin and the Management of Iron Deficiency Anemia in Chronic Kidney Disease

“…Inflammation is characteristic feature of CKD and caused by multiple factors of the toxic uremic milieu and the dialysis procedure itself. The interpretation of iron biomarkers is hindered by inflammation, which can directly affect the concentrations of most iron biomarkers [ 14 ], including ferritin and hepcidin [ 16 , 17 , 18 ]. Inflammation-mediated increase in hepcidin leads to iron trapping within the macrophages and hepatocytes, resulting in FID [ 19 ].…”