Plasma FGF23 levels and heart rate variability in patients with stage 5 CKD

Zhang, L.-N.; Yang, Guang; Chen, Cheng; Shen, Chong; Chen, Ying; Zhang, J.; Shen, Zhi-Xiang; Zhang, Ming; Ge, Yifei; Sun, Bin; Yu, Xiangbao; Ouyang, Chun; Zhang, Bin; Mao, Huijuan; Liu, J.; Xing, Changying; Zha, Xiaoming; Wang, N.-N.

doi:10.1007/s00198-014-2862-7

Cited by 19 publications

(18 citation statements)

References 41 publications

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“…A very recent study has hypothesized that a single FGF23 measurement itself is enough of a prognostic tool to predict complications, mortality and the clinical course in patients undergoing elective cardiac surgery [17]. Similarly, another study reported that the FGF23 level in stage 5 was much higher in patients with severe secondary hyperparathyroidism and independently associated with decreased heart rate variability [18]. In our study cohort, the FGF23 level of 50% of patients in stage 5 was >1,000 pg/ml, and 30% of them have coronary artery disease and 50% secondary hyperparathyroidism as coexisting conditions.…”

Section: Discussionmentioning

confidence: 99%

Elevated Fibroblast Growth Factor 23 Concentration: Prediction of Mortality among Chronic Kidney Disease Patients

et al. 2015

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Background: The osteocyte-derived hormone, fibroblast growth factor 23 (FGF23), regulates the phosphorus metabolism and suppresses 1,25-dihydroxyvitamin D production, thereby mitigating hyperphosphatemia in patients with renal disorders. An elevated FGF23 level is suggested to be an early biomarker of altered phosphorus metabolism in the initial stages of chronic kidney disease (CKD) and acts as a strong predictor of mortality in dialysis patients. In the Saudi population, there is no report on the FGF23 level in CKD patients to date. This study aims to estimate the plasma FGF23 levels in the Saudi population and to correlate it with its clinical manifestations in order to ascertain its role in the pathogenesis of CKD patients. Methods: The FGF23 level in the plasma samples was determined using ELISA in a diverse cohort of 89 cases with stage 3-5 CKD and 100 healthy subjects. The plasma FGF23 level was correlated with other biochemical parameters. Results: The results revealed that the FGF23 level was markedly elevated among CKD patients compared to the control group, and a significant inverse correlation was observed between the FGF23 level and glomerular filtration rate. FGF23 elevation was approximately 40-fold among stage 5 patients compared to the control, while the elevation of phosphate, parathyroid hormone (PTH) and alkaline phosphatase was 2-, 3- and 8-fold in this stage, respectively. Conclusion: Elevated FGF23 levels may have a strong correlation with the disease pathogenesis. In addition, FGF23 might be a future therapeutic target to intervene against the progression of CKD as well as to increase patient survivability.

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Section: Discussionmentioning

confidence: 99%

Elevated Fibroblast Growth Factor 23 Concentration: Prediction of Mortality among Chronic Kidney Disease Patients

et al. 2015

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“…After PTX, obvious elevation of serum leptin in SHPT was only observed in the lowest group across quartiles of lnleptin/BMI (Q1 group). In the Q3 and Q4 groups, CKD patients had mildly improved HRV after PTX, which might be due to the normalization of bone metabolism disorders such as high levels of circulating fibroblast growth factor 23 and PTH levels [20,46] . Some studies suggested that PTH affects the Akt signaling in adipocytes [48][49][50] , which is an independent pathway in leptin release [51] .…”

Section: Discussionmentioning

confidence: 99%

“…Our results suggested that iPTH was related to the imbalance of cardiac autonomic nervous function. As the prior therapy for severe SHPT [47] , PTX could not only correct the abnormal bone metabolism disorders but also improve the decreased HRV [20] . After PTX, obvious elevation of serum leptin in SHPT was only observed in the lowest group across quartiles of lnleptin/BMI (Q1 group).…”

Section: Discussionmentioning

confidence: 99%

“…HRV was determined using a Holter electrocardiogram (MARS-PC; GE Company, Fairfield, Conn., USA) and analyzed using custom-made Marquetter analytical software, as previously described [4,20] . Time domain variables included mean normalto-normal R-R intervals (mean NN), the SD of NN (SDNN), SD of 5-minute average of NN (SDANN), root mean square of differences between adjacent NN (rMSSD), and proportion of adjacent NN differing by >50 ms over 24 h (pNN50%).…”

Section: Analysis Of Hrvmentioning

confidence: 99%

“…HRV in severe SHPT was lower than in CKD patients without SHPT [4] with the underlying mechanisms remaining unclear. As an efficient therapy for severe SHPT patients, parathyroidectomy (PTX) could reverse lower HRV and reduce CVD mortality [4,20,21] , while the role of circulating leptin in this process is also obscure.…”

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confidence: 99%

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Parathyroidectomy Increases Heart Rate Variability and Leptin Levels in Patients with Stage 5 Chronic Kidney Disease

Jiang¹,

Shen

Zhang³

et al. 2016

Am J Nephrol

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Background: In chronic kidney disease (CKD) patients, decreased heart rate variability (HRV) reflects impaired cardiac automatic nervous function and high risk of cardiovascular disease (CVD). Lower HRV in patients with severe secondary hyperparathyroidism (SHPT), a clinical manifestation of CKD-mineral and bone disorder (CKD-MBD), could be reversed by parathyroidectomy (PTX). It has been proved that leptin interacts with the autonomic nervous function. However, the associations between leptin and HRV in CKD patients and their longitudinal changes in SHPT patients after PTX are still unknown. Methods: This was a cross-sectional study including 141 stage 5 CKD patients, and a prospective study in 36 severe SHPT patients with PTX. HRV was measured by Holter and serum leptin was measured by ELISA. Serum leptin levels were adjusted for body mass index (BMI) and transformed using natural logarithm (lnleptin/BMI). Results: With a gradient of lnleptin/BMI across quartiles from Q1 to Q4 in CKD patients, HRV indices showed no differences among quartiles. Patients in Q1 group had higher mean 24 h heart rates, and lower ln(very low frequency) (lnVLF) than other quartiles, although there were no statistically significant difference. In multivariate stepwise regression, serum leptin/BMI was an independent predictor for low frequency/high frequency. HRV indices and lnleptin/BMI levels were increased in severe SHPT patients after PTX. Compared to other quartiles, SHPT patients in Q1 group had larger improvement of lnVLF after PTX. Conclusion: Circulating leptin levels may be a novel treatment target to reduce CVD risk in advanced CKD-MBD patients.

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The suppressive effect of soluble Klotho on fibroblastic growth factor 23 synthesis in UMR‐106 osteoblast‐like cells

Gao

et al. 2018

Cell Biology International

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Fibroblastic growth factor 23 (FGF23) is a hormone secreted primarily by bone. FGF23 is elevated in the serum of chronic kidney disease (CKD) patients, but the exact mechanism is not well known. Klotho is identified as an aging suppressor, which is mainly expressed in the kidney, and the level of soluble Klotho is negatively associated with FGF23 in CKD. The aim of this study was to investigate the effect and possible mechanism of Klotho on FGF23 synthesis in osteoblast-like UMR-106 cells. UMR-106 cells were divided into five groups: (i) control group; (ii) β-glycerophosphate (β-GP) group; (iii) β-GP + Klotho group; (iv) β-GP+ lithium chloride (LiCl, a Wnt/β-catenin pathway agonist) group; and (v) β-GP + Klotho + LiCl group. Subsequently, UMR-106 cells were cultured for 72 h, and the expression of FGF23, P-glycogen synthase kinase-3β (P-GSK-3β), and glycogen synthase kinase-3β(GSK-3β) were measured with Western blot analysis. The mRNA levels of FGF23 and the Wnt/β-catenin pathway target gene c-myc were determined with RT-qPCR. The results showed that β-GP induced increased expression of FGF23 mRNA and protein. Compared with the β-GP group, expression of FGF23 mRNA and protein expression were downregulated in the β-GP + Klotho group. In addition, β-GP induced increased expression of P-GSK-3β/GSK-3β and c-myc, which were all downregulated in the β-GP + Klotho group. Moreover, the expression of FGF23, P-GSK-3β/GSK-3β, and c-myc mRNA were upregulated when treated with LiCl. These results demonstrate that soluble Klotho suppresses FGF23 synthesis in osteoblast-like UMR-106 cells. The mechanism of this suppression may be partially through the inhibition of the Wnt/β-catenin pathway.

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Plasma FGF23 levels and heart rate variability in patients with stage 5 CKD

Cited by 19 publications

References 41 publications

Elevated Fibroblast Growth Factor 23 Concentration: Prediction of Mortality among Chronic Kidney Disease Patients

Elevated Fibroblast Growth Factor 23 Concentration: Prediction of Mortality among Chronic Kidney Disease Patients

Parathyroidectomy Increases Heart Rate Variability and Leptin Levels in Patients with Stage 5 Chronic Kidney Disease

The suppressive effect of soluble Klotho on fibroblastic growth factor 23 synthesis in UMR‐106 osteoblast‐like cells

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