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. 2023 Nov 30;38(12):2713-2722.
doi: 10.1093/ndt/gfad096.

Association between serum iron markers, iron supplementation and cardiovascular morbidity in pre-dialysis chronic kidney disease

Takeshi Hasegawa  1   2   3   4 , Takahiro Imaizumi  5   6 , Takayuki Hamano  7   8 , Kenta Murotani  9 , Naohiko Fujii  10 , Hirotaka Komaba  11 , Masahiko Ando  5 , Shoichi Maruyama  6 , Masaomi Nangaku  12 , Kosaku Nitta  13 , Hideki Hirakata  14 , Yoshitaka Isaka  8 , Takashi Wada  15 , Masafumi Fukagawa  11
Affiliations

Association between serum iron markers, iron supplementation and cardiovascular morbidity in pre-dialysis chronic kidney disease

Takeshi Hasegawa et al. Nephrol Dial Transplant. .

Abstract

Background: The optimal range of serum iron markers and usefulness of iron supplementation are uncertain in patients with pre-dialysis chronic kidney disease (CKD). We investigated the association between serum iron indices and risk of cardiovascular disease (CVD) events and the effectiveness of iron supplementation using Chronic Kidney Disease Japan Cohort data.

Methods: We included 1416 patients ages 20-75 years with pre-dialysis CKD. The tested exposures were serum transferrin saturation and serum ferritin levels and the outcome measures were any cardiovascular event. Fine-Gray subdistribution hazard models were used to examine the association between serum iron indices and time to events. The multivariable fractional polynomial interaction approach was used to evaluate whether serum iron indices were effect modifiers of the association between iron supplementation and cardiovascular events.

Results: The overall incidence rate of CVD events for a median of 4.12 years was 26.7 events/1000 person-years. Patients with serum transferrin saturation <20% demonstrated an increased risk of CVD [subdistribution hazard ratio (HR) 2.13] and congestive heart failure (subdistribution HR 2.42). The magnitude of reduction in CVD risk with iron supplementation was greater in patients with lower transferrin saturations (P = .042).

Conclusions: Maintaining transferrin saturation >20% and adequate iron supplementation may effectively reduce the risk of CVD events in patients with pre-dialysis CKD.

Keywords: CKD; cardiovascular disease; iron deficiency; iron supplementation; pre-dialysis.

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Conflict of interest statement

T.Hasegawa, H.K., M.N., K.N., Y.I. and TW have consultancy agreements with and received honoraria from Kyowa Hakko Kirin. T.I. received a research grant and honoraria from Kyowa Hakko Kirin. M.A. received a research grant from Kyowa Hakko Kirin. T.Hamano and M.F. have consultancy agreements with Kyowa Hakko Kirin and received honoraria and a research grant from Kyowa Hakko Kirin. All remaining authors have nothing to disclose.

Figures

Graphical Abstract
Graphical Abstract
Figure 1:
Figure 1:
Selection process of the analysed participants.
Figure 2:
Figure 2:
Event-free survival curves for CVD/CHF by serum iron indices categories.
Figure 3:
Figure 3:
TSAT or serum ferritin levels and CVD or CHF risk. Fine–Gray subdistribution hazard models were employed to examine the association between serum TSAT or ferritin levels and time to event with the consideration of death not due to CVD and dialysis initiation, i.e. developing ESKD as competing risks. All models were stratified by facilities and adjusted for potential confounders as follows: age, sex, BMI, smoking status, SBP, diabetes mellitus, history of any CVD, eGFR, UACR, haemoglobin, serum albumin, serum calcium, serum phosphorus, iPTH, ESAs, iron supplementation, RAS inhibitors, β-blockers and CCBs.
Figure 4:
Figure 4:
Effect of iron supplementation on CVD risk by TSAT levels.
See this image and copyright information in PMC

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