Long-term iron accumulation in dialysis patients treated with ferric citrate hydrate: a single-center, 80-week retrospective study in Japan

Abstract

Background: Ferric citrate hydrate (FCH), an iron-based phosphate binder, affects mineral and iron metabolism in patients with chronic kidney disease (CKD). The long-term impact of FCH on iron overload is unknown. With this study, we investigated whether the type of dialysis is associated with FCH-related iron accumulation. Methods: This single-center, retrospectively registered, cohort study was performed in Kariya-Toyota General Hospital, Japan, among outpatients undergoing maintenance hemodialysis (HD) or peritoneal dialysis (PD) between July 2014 and January 2017. It included 136 subjects receiving FCH treatment (104 HD patients and 32 PD patients). Their iron metabolism parameters and FCH-associated adverse events were assessed over 80 weeks. Results: In both groups, the weekly darbepoetin alpha dose and erythropoiesis resistance index declined significantly by 16 weeks, although mean hemoglobin concentrations remained stable (10-11 g/dL), and transferrin saturation peaked at 24 weeks. The difference in the weekly darbepoetin alpha dose for HD and PD patients was 16.5 and 12. 0 μg/week, respectively, (P < 0.01). Increases in iron stores were different between the two groups. Peak mean increase in serum ferritin levels (169.0 vs. 63.0 ng/mL, respectively; P = 0.001) in PD patients at 40 weeks was significantly earlier than that in HD patients. The adverse events observed suggest that FCH treatment was more likely to be discontinued within the first 16 weeks due to hemoglobin overshooting in HD patients and after 40 weeks due to ferritin overload in PD patients. Conclusions: Oral iron supplementation with FCH was successful in all dialysis patients. However, the type of dialysis is a major factor associated with iron accumulation during long-term FCH treatment and more likely to occur in PD patients not experiencing regular, dialysis-associated iron loss. Therefore, the method of dialysis should be taken into consideration when evaluating iron stores of patients with CKD to determine the appropriate starting dose of FCH.

Biochemical markers of iron status and iron accumulation in peritoneal dialysis patients treated with ferric citrate

“…21,22 Other reports have too documented clinically significant iron accumulation in PD patients treated with ferric citrate, a unique population that might have been underrepresented in the studies evaluating the safety and efficacy of ferric citrate. [18][19][20] An interesting finding was the dissociation between ferritin and transferrin saturation observed in this cohort. While ferritin values increased over time in patients treated with ferric citrate, the transferrin saturation did not parallel this increase.…”

“…21,22 Other reports have too documented clinically significant iron accumulation in PD patients treated with ferric citrate, a unique population that might have been underrepresented in the studies evaluating the safety and efficacy of ferric citrate. 18–20…”

“…Additionally, when compared to haemodialysis, patients receiving PD treated with ferric citrate exhibited higher levels of serum ferritin suggesting progressive iron absorption. [18][19][20] Appropriate and safe ferritin levels in dialysis patients have been a contested issue with conflicting literature. 21,22 Recent reports suggest that patients receiving PD with sustained elevated ferritin levels exceeding 800 ng/mL are at a higher risk of death.…”

“…Additionally, when compared to haemodialysis, patients receiving PD treated with ferric citrate exhibited higher levels of serum ferritin suggesting progressive iron absorption. 18–20…”