Serum fibroblast growth factor–21 concentration is associated with residual renal function and insulin resistance in end-stage renal disease patients receiving long-term peritoneal dialysis
Introduction
Patients with end-stage renal disease (ESRD) show insulin resistance [1]. Insulin resistance is significantly associated with the progression of atherosclerosis and may predict cardiovascular mortality in this population [2]. High glucose exposure exerts detrimental effects on the peritoneal membrane in patients treated with peritoneal dialysis (PD), and a substantial amount of glucose is absorbed via the peritoneal capillary vessels. This may further aggravate insulin resistance in PD patients, although they are not classified as having diabetes [3].
Fibroblast growth factors (FGFs) are classified into 7 families and are involved in a variety of cellular functions including cell survival, differentiation, mitosis, and angiogenesis. The FGF-19 families (FGF-19, FGF-21, and FGF-23) function as metabolic regulators of glucose metabolism and mineral homeostasis. Fibroblast growth factor–21 is produced in the liver but acts mainly on white adipose tissue because of its receptor specificity for FGF receptors [4]. However, several studies suggest that FGF-21 could be expressed in pancreas, skeletal muscle, and various cells [5], [6]. Recent studies show that FGF-21 increases glucose uptake in adipose tissue, ameliorates diet-induced obesity, and regulates hepatic lipid metabolism in ketotic states by activating peroxisome proliferator-activated receptor–α[7], [8], [9], [10], [11]. Human studies [12], [13], [14] show a potential relationship between FGF-21 level and obesity. However, more studies are needed to clarify the clinical role of FGF-21 in humans.
It is not understood clearly whether serum FGF-21 contributes to the detrimental metabolic status in patients with chronic kidney disease. Only one report has shown that serum FGF-21 concentration correlates with renal function and is elevated markedly in patients receiving hemodialysis, suggesting a possible link between FGF-21 concentration and its renal excretion [15]. Given the potential effects of FGF-21 as an endocrine factor involved in the regulation of glucose homeostasis [8], [9], [10], [13], we hypothesized that this circulating protein plays a role in insulin resistance in nondiabetic, ESRD patients receiving PD. However, the relationship between serum FGF-21 concentration and insulin resistance has not been explored in patients receiving PD. We performed this study to identify which factors are associated with FGF-21 concentration and to elucidate whether FGF-21 plays a role in insulin resistance in nondiabetic ESRD patients undergoing PD.
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Study subjects and data collection
The study included 156 regular PD patients at the dialysis clinic of Yonsei University Medical Center, Seoul, Korea, between 2006 and 2007. Because we aimed to investigate the metabolic effects of FGF-21 in ESRD patients who exhibited insulin resistance induced by uremia per se, 55 patients with diabetes were excluded from our study. Patients younger than 18 years or who had been maintained on PD for less than 3 months were also excluded. Patients were considered eligible for this study if they
Comparison of demographic and clinical parameters between healthy subjects and nondiabetic patients undergoing PD
Baseline characteristics of the 72 PD patients and 63 healthy controls with normal renal function were presented in Table 1. Age and sex were well matched between the 2 groups. Among the patients treated with PD, chronic glomerulonephritis was the most common cause of ESRD (48.6%), followed by hypertension (26.4%); and only 5 patients (6.9%) had previous CVD. The PD patients had higher mean systolic BP (132.8 ± 19.8 vs 114.1 ± 12.9 mm Hg, P < .001) and diastolic BP (80.5 ± 9.7 vs 70.0 ± 10.8 mm
Discussion
Although several human studies have investigated the clinical significance of FGF-21 [13], [14], [15], the clinical role of FGF-21 is understood incompletely; and it would be of great value to elucidate the function of this new metabolic regulator in humans. In the present study, we investigated (1) the relationship between metabolic parameters and serum FGF-21 concentrations in people with normal and impaired renal function, (2) whether FGF-21 concentration is related to residual renal
Acknowledgment
This work was supported by grants from the Seoul R&BD program to Choi SH, Republic of Korea (10526).
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The association of circulating fibroblast growth factor 21 levels with incident heart failure: The Multi-Ethnic Study of Atherosclerosis
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2021, Metabolism: Clinical and ExperimentalCitation Excerpt :In general, the studies corroborate an inverse relationship between GFR and FGF21 and point to renal clearance as an important route through which this small protein, passing through the glomerular barrier, is filtered and excreted in the urine [17]. When compared to normal subjects, serum FGF21 levels were 15-fold higher in patients receiving long-term HD [102], 8-fold higher in those on peritoneal dialysis (PD) [107] and 10–20-fold higher in ESRD patients [103,104]. In clinically apparently healthy adults, high FGF21 levels were associated with lower estimated GFR and higher urinary albumin/creatinine ratio.
Fibroblast growth factor 21 in lipid metabolism and non-alcoholic fatty liver disease
2019, Clinica Chimica ActaFibroblast growth factor 21: A role in cardiometabolic disorders and cardiovascular risk prediction?
2019, Metabolism: Clinical and ExperimentalFibroblast growth factor 21 in chronic kidney disease
2019, Clinica Chimica ActaCitation Excerpt :Stein et al. found that serum FGF21 levels were elevated 15-fold in patients receiving long-term hemodialysis [48]. Similarly, a more recent study by Han et al. found that serum FGF21 concentrations were increased 8-fold in patients receiving peritoneal dialysis compared to healthy control subjects [49]. In agreement with these findings, Lin et al. proposed that serum FGF21 concentration gradually increase as CKD progresses from early- to end-stage disease, with data indicating that serum FGF21 levels were elevated 10-fold in patients with ESRD in comparison to healthy participants [50].