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

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.

The interaction analysis between advanced age and longer dialysis vintage on the survival of patients receiving maintenance hemodialysis

“…A recent clinical study showed that low transferrin saturation and a high ferritin concentration are predictors of cerebrovascular and cardiovascular disease and mortality in patients undergoing MHD. 25 Notably, we have shown that low TIBC and platelet count are associated with a higher risk of all-cause mortality. Iron use disorders would aggravate any anemia, and thrombocytopenia would increase the risks of bleeding and infection.…”

Post-mortem liver and bone marrow iron quantification in haemodialysis patients: A prospective cohort study

“…40 , 41 , 42 Besides, iron-laden macrophages are known to be a proatherogenic phenotype, 43 and their presence in haemodialysis patients may add to the already elevated risk of atherogenesis. 44 , 45 , 46 …”

Efficacy and Safety of Daprodustat Vs rhEPO for Anemia in Patients With Chronic Kidney Disease: A Meta-Analysis and Trial Sequential Analysis

“…Among CKD patients, TSAT ≤20% could be found in patients with absolute iron deficiency or functional iron deficiency (also known as iron-restricted erythropoiesis) ( Gafter-Gvili et al, 2019 ). Also, studies have shown that low TSAT levels are related to an increased risk of cerebrovascular and cardiovascular disease (CCVD) and death compared to patients with normal or higher TSAT levels ( Kuragano et al, 2020 ). Therefore, the increasing level of TSAT, TIBC and total iron suggested that daprodustat may be superior to rhEPO in optimizing iron metabolism for the treatment of anemia in DD-CKD patients.…”