MO547ASSOCIATION BETWEEN SERUM INDICES OF IRON METABOLISM AND CARDIOVASCULAR MORBIDITY IN PATIENTS WITH PREDIALYSIS CHRONIC KIDNEY DISEASE
Authors: Hasegawa Takeshi , Imaizumi Takahiro , Murotani Kenta , Hamano Takayuki , Fukagawa Masafumi 
Published: May 2021

Abstract

Background and Aims
Patients with predialysis chronic kidney disease (CKD) have a greater risk of developing cardiovascular disease (CVD) events than the general population. Anaemia is the most frequent comorbidity in pre-dialysis CKD patients and is associated with an increase in CVD events. Iron deficiency is the most frequent cause of erythropoiesis-stimulating agents (ESAs) resistant anaemia in CKD patients and is modifiable by therapeutic intervention. However, the optimal ranges of iron markers are uncertain in predialysis CKD patients. Therefore, we aimed to investigate the association between serum indices of iron metabolism and the incidence of CVD events in patients with predialysis CKD using the CKD-Japan Cohort (CKD-JAC) data.

Method
We prospectively followed 1550 CKD patients aged 20-75 years with an estimated glomerular filtration rate (eGFR) &lt;60 mL/min/1.73 m2 for a mean of 4.21 years. We set serum transferrin saturation (TSAT) and ferritin levels as the main exposures to be tested. Our main outcome measures were any of the CVD events including fatal or non-fatal myocardial infarction, congestive heart failure (CHF), angina pectoris, arrhythmia, aorta dissection, cerebrovascular disorder, and peripheral artery diseases identified at each facility and adjudicated by the independent cardiac function evaluation committee. Multivariable Cox proportional hazards regression models were employed to examine the association between serum TSAT or ferritin levels with time to events. Death was considered as a competing risk with the Fine and Gray model. All models were stratified by facilities and adjusted for potential confounders as follows: age, sex, systolic blood pressure, diabetes mellitus, history of CHF, haemoglobin, serum calcium, serum phosphorus, intact parathyroid hormone, eGFR, proteinuria, ESAs, iron supplementation, renin-angiotensin system inhibitors, and beta-blockers. We also applied the multivariable fractional polynomial interaction (MFPI) approach to investigate whether TSAT levels are the effect modifier of the association between iron supplementation and the outcomes.

Results
In the overall cohort, 208 (13.4 %) patients developed CVD events (including 97 CHF) during the follow-up period (26.6 events/1000 person-year). The incidence rate of CVD events was the highest in the TSAT &lt; 20% category (33.0 events/1000 person-year). Compared to patients in the TSAT &gt; 40% category, those in the TSAT &lt; 20% category demonstrated an increased risk of CVD events (adjusted hazard ratio (AHR): 1.86, 95% confidence interval (CI): 1.06-3.26) and CHF events (AHR: 2.82, 95% CI: 1.15-6.89), respectively. Meanwhile, there was no association between serum ferritin levels and the risk of developing CVD or CHF events. MFPI analyses showed a reduced risk of CVD in patients receiving iron supplementation only in patients with TSAT &lt;20% (P for interaction=0.02).

Conclusion
Maintaining TSAT &gt;20% could be effective to reduce the risk of developing CVD events (especially CHF) in patients with predialysis CKD. Our analyses also suggest that iron-deficient patients with predialysis CKD may benefit from iron supplementation for reduced risk of CVD events.