Low transferrin saturation (TSAT) and high ferritin levels are significant predictors for cerebrovascular and cardiovascular disease and death in maintenance hemodialysis patients.

Takahiro Kuragano,Nobuhiko Joki,Yukihiro Itakura,Toru Inoue,Atushi Fukatsu,Takeshi Nakanishi,Toshiaki Murata,Kenichiro Kitamura,Shouichi Fujimoto,Hiroki Hase,Pavel Strnad

doi:10.1371/journal.pone.0236277

Abstract

Patients with high serum ferritin and low transferrin saturation (TSAT) levels could be considered as presenting with dysutilization of iron for erythropoiesis. However, the long-term safety of iron administration in these patients has not been well established. An observational multicenter study was performed over 3 years. In 805 patients undergoing maintenance hemodialysis (MHD), we defined dysutilization of iron for erythropoiesis in patients with lower TSAT (<20%) and higher ferritin (≥100 ng/mL) levels. A time-dependent Cox hazard model was used for the evaluation of the association between dysutilization of iron for erythropoiesis and adverse events and survival. Patients with low TSAT levels showed an increased risk of cerebrovascular and cardiovascular disease (CCVD) and death compared to patients with normal or higher TSAT levels. Patients with low ferritin and high TSAT levels had a significantly lower risk of CCVD and death compared with patients with high ferritin and low TSAT levels. Higher TSAT levels were associated with male gender, age, the absence of diabetes, low levels of high-sensitivity CRP, and low β2 microglobulin levels, but not with intravenous iron administration or ferritin levels. Although patients with low TSAT levels had a significantly higher risk of CCVD or death, high TSAT levels were not linked with iron administration. Patients, who were suspected of dysutilization of iron for erythropoiesis, had a higher risk of CCVD and death. The administration of iron should be performed cautiously for improving TSAT levels, as iron administration could sustain TSAT levels for a short term.

Highlights

Several international guidelines [1,2] regarding the treatment of anemia with chronic kidney disease have recommended ferritin and Transferrin saturation (TSAT) as indexes of iron status, as well as markers for the initiation and cessation of iron supplementation in CKD patients
The Dialysis Patients Response to IV Iron with Elevated Ferritin (DRIVE) study reported the efficacy of intravenous iron administration in the improvement of Hb levels in maintenance hemodialysis (MHD) patients who had ferritin levels of 500–1200 ng/mL and TSAT levels under 25%, i.e., in those who were suspected of dysutilization of iron for erythropoiesis [7]
erythropoiesis-stimulating agents (ESA) or IV iron administration was performed according to the 2008 Japanese Society for Dialysis Therapy: Guidelines for Renal Anemia in Chronic Kidney Disease [11]

Summary

Introduction

Several international guidelines [1,2] regarding the treatment of anemia with chronic kidney disease have recommended ferritin and TSAT as indexes of iron status, as well as markers for the initiation and cessation of iron supplementation in CKD patients. The dysutilization of iron for erythropoiesis is a state in which there is insufficient iron incorporation into erythroid precursors in the face of apparently adequate body iron stores [4]. This condition is seen in patients with infectious diseases, chronic inflammation, chronic heart disease, chronic kidney disease, and malignant disease [5,6]. A recent meta-analysis based on 34 studies involving a total of 2,658 MHD patients demonstrated that administration of intravenous iron to patients with serum ferritin levels >200 ng/mL with or without a TSAT

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