Circulating Fibroblast Growth Factor-23 Levels are Associated with an Increased Risk of Anemia Development in Patients with Nondialysis Chronic Kidney Disease

Ki Heon Nam,Seong Yeong An,Min-Uk Cha,Hyoungnae Kim,Kyu-Beck Lee,Misol Lee,Kyu Hun Choi,Yeong-Hoon Kim,Seung Hyeok Han,Joongyub Lee,Tae-Hyun Yoo,Su-Ah Sung,Jung Tak Park,Shin-Wook Kang,Curie Ahn

doi:10.1038/s41598-018-25439-z

Abstract

Fibroblast growth factor-23 (FGF23) is an established biomarker of adverse outcomes in patients with chronic kidney disease (CKD). Several cross-sectional studies have suggested a possible association between FGF23 and anemia in these patients. In this large-scale prospective cohort study, we investigated this relationship and examined whether high FGF23 levels increase the risk of incident anemia. This prospective longitudinal study included 2,089 patients from the KoreaN cohort study for Outcome in patients With CKD. Anemia was defined as hemoglobin level <13.0 g/dl (men) and <12.0 g/dl (women). Log-transformed FGF23 significantly correlated with hepcidin but inversely correlated with iron profiles and hemoglobin. Multivariate logistic regression showed that log-transformed FGF23 was independently associated with anemia (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.04–1.24, P = 0.01). Among 1,164 patients without anemia at baseline, 295 (25.3%) developed anemia during a median follow-up of 21 months. In fully adjusted multivariable Cox models, the risk of anemia development was significantly higher in the third (hazard ratio [HR], 1.66; 95% CI, 1.11–2.47; P = 0.01) and fourth (HR, 1.84; 95% CI, 1.23–2.76; P = 0.001) than in the first FGF23 quartile. In conclusion, high serum FGF23 levels were associated with an increased risk for anemia in patients with nondialysis CKD.

Highlights

Anemia is one of the most common complications in chronic kidney disease (CKD), and its prevalence increases progressively as kidney function declines[1]
We investigated the relationship between Fibroblast growth factor-23 (FGF23) and the development of anemia in several subgroups stratified by age, sex, presence of diabetes, systolic BP (SBP), body mass index (BMI), Charlson comorbidity index (CCI), estimated glomerular filtration rate (eGFR), albumin, 1,25(OH)[2] vitamin D, C-reactive protein (CRP), and iron deficiency status
P-for trend respect to anemia in most stratified groups (Fig. 4). This association was observed in nondiabetics, patients aged

Summary

Introduction

Anemia is one of the most common complications in chronic kidney disease (CKD), and its prevalence increases progressively as kidney function declines[1]. Anemia is closely associated with poor quality of life and adverse outcomes such as left ventricular hypertrophy, cardiovascular events, and increased mortality in patients with CKD3–5. Elevated FGF23 levels have been shown to be associated with adverse outcomes, such as progression of kidney disease[13,14], vascular calcification[15], left ventricular hypertrophy[16], cardiovascular events[17,18], and increased mortality[14,17,19]. Considering that FGF23 and anemia are nontraditional risk factors for adverse outcomes in patients with CKD, and both are reciprocally changed according to kidney function, it would be intriguing to explore the relationship between FGF23 and anemia in CKD. The purpose of this study was, to further clarify the relationship between FGF23 levels and anemia in patients with CKD and to examine whether high FGF23 levels increase the future development of anemia, in a large-scale prospective cohort study

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