Circulating Levels of Soluble Klotho and Fibroblast Growth Factor 23 in Diabetic Patients and Its Association with Early Nephropathy

Farías-Basulto, Alfonso; Martínez-Ramírez, Héctor R.; Gómez-García, Erika F.; Cueto-Manzano, Alfonso M.; Cortés-Sanabria, Laura; Hernández-Ramos, Luis Eduardo; Ramírez-López, Guadalupe; Mendoza-Carrera, Francisco

doi:10.1016/j.arcmed.2019.01.008

Cited by 11 publications

(13 citation statements)

References 23 publications

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“…The absolute circulating FGF23 levels measured in this study were different from that obtained by Robinson-Cohen et al This study used Duoset ELISA Development kit (R&D system, Inc.) to measure intact FGF23 levels; and the median intact FGF23 level in the studied population was 360 (110-1,740) pg/ml (expressed as median and interquartile range). For published researches using this ELISA kit, the median of intact FGF23 level was 269.9 (109.2-1,014.0) pg/ml in Chinese renal transplant donors 41 , and 150 (46-583) pg/ml in Mexicans with normal kidney function 42 . In contrary, Robinson-Cohen et al used a different ELISA kit (Kainos Laboratories, Inc., Tokyo, Japan), and the population for their study was of European ancestry.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association study for circulating fibroblast growth factor 21 and 23

Chuang

Liu

Chyan

et al. 2020

Sci Rep

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Fibroblast growth factors (FGFs) 21 and 23 are recently identified hormones regulating metabolism of glucose, lipid, phosphate and vitamin D. Here we conducted a genome-wide association study (GWAS) for circulating FGF21 and FGF23 concentrations to identify their genetic determinants. We enrolled 5,000 participants from Taiwan Biobank for this GWAS. After excluding participants with diabetes mellitus and quality control, association of single nucleotide polymorphisms (SNPs) with log-transformed FGF21 and FGF23 serum concentrations adjusted for age, sex and principal components of ancestry were analyzed. A second model additionally adjusted for body mass index (BMI) and a third model additionally adjusted for BMI and estimated glomerular filtration rate (eGFR) were used. A total of 4,201 participants underwent GWAS analysis. rs67327215, located within RGS6 (a gene involved in fatty acid synthesis), and two other SNPs (rs12565114 and rs9520257, located between PHC2-ZSCAN20 and ARGLU1-FAM155A respectively) showed suggestive associations with serum FGF21 level (P = 6.66 × 10-7 , 6.00 × 10-7 and 6.11 × 10-7 respectively). The SNPs rs17111495 and rs17843626 were significantly associated with FGF23 level, with the former near PCSK9 gene and the latter near HLA-DQA1 gene (P = 1.04 × 10-10 and 1.80 × 10-8 respectively). SNP rs2798631, located within the TGFB2 gene, was suggestively associated with serum FGF23 level (P = 4.97 × 10-7). Additional adjustment for BMI yielded similar results. For FGF23, further adjustment for eGFR had similar results. We conducted the first GWAS of circulating FGF21 levels to date. Novel candidate genetic loci associated with circulating FGF21 or FGF23 levels were found. Further replication and functional studies are needed to support our findings. Fibroblast growth factor (FGF) superfamily includes 22 family members. Except for the endocrine FGF19, FGF21, and FGF23, other family members act as autocrine or paracrine factors 1. Recent evidence showed that FGF21 exerts metabolic effects by acting both centrally and peripherally, mostly in the liver, adipose tissue and pancreas. In prolonged starvation, FGF21 is secreted by the liver to promote gluconeogenesis, increases hepatic

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Section: Discussionmentioning

confidence: 99%

Genome-wide association study for circulating fibroblast growth factor 21 and 23

Chuang

Liu

Chyan

et al. 2020

Sci Rep

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“…High FGF-23 levels reduce the risk of early development of kidney disease in patients with type 2 diabetes mellitus in the absence of other intervening risk factors. 122 It is thought that FGF23 induces inflammation by disrupting phosphate metabolism. Inhibition of FGF-23 relieves DN by increasing peripheral insulin sensitivity and enhancing subcutaneous glucose tolerance.…”

Section: The Relationship Between Fibroblast Growth Factor and Diabetic Nephropathymentioning

confidence: 99%

The Multiple Roles of Fibroblast Growth Factor in Diabetic Nephropathy

Deng¹,

Liu²,

Liu³

et al. 2021

JIR

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Diabetic nephropathy (DN) is a common microvascular complication in the late stages of diabetes. Currently, the etiology and pathogenesis of DN are not well understood. Even so, available evidence shows its development is associated with metabolism, oxidative stress, cytokine interaction, genetic factors, and renal microvascular disease. Diabetic nephropathy can lead to proteinuria, edema and hypertension, among other complications.In severe cases, it can cause life-threatening complications such as renal failure. Patients with type 1 diabetes, hypertension, high protein intake, and smokers have a higher risk of developing DN. Fibroblast growth factor (FGF) regulates several human processes essential for normal development. Even though FGF has been implicated in the pathological development of DN, the underlying mechanisms are not well understood. This review summarizes the role of FGF in the development of DN. Moreover, the association of FGF with metabolism, inflammation, oxidative stress and fibrosis in the context of DN is discussed. Findings of this review are expected to deepen our understanding of DN and generate ideas for developing effective prevention and treatments for the disease.

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“…As the concentration of sKlotho increased, it exerted a protective effect on renal endothelial cells (9,10). However, in the early stage of DN in patients with normal renal function, the change in sKlotho remains controversial (11)(12)(13)(14)(15). Therefore, this study aimed to investigate the relationship between the sKlotho levels and DN, especially its relationship with the early stage of DN to guide clinical treatment and prognosis.…”

Section: Introductionmentioning

confidence: 99%

Relationship of Soluble Klotho and Early Stage of Diabetic Nephropathy: A Systematic Review and Meta-Analysis

Xin

Sun

et al. 2022

Front. Endocrinol.

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BackgroundDiabetic nephropathy (DN) is a chronic microvascular complication caused by long-term hyperglycemia in patients with diabetes and an important cause of end-stage renal disease. Although some studies have shown that soluble Klotho(sKlotho) levels of patients with DN are lower than those without DN, in the early stage of patients with DN with normal renal function and albuminuria, the change in sKlotho is still controversial.AimThis meta-analysis was conducted to statistically evaluate sKlotho levels in patients with DN.MethodsWe searched the following electronic databases: Web of Science, Embase, PubMed, Google Scholar, and China National Knowledge Infrastructure (CNKI). The following search terms were used for the title or abstract: “diabetic kidney disease”, “diabetic nephropathy”, OR “DN” in combination with “Klotho”. The meta-analysis results were presented as standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs).ResultsFourteen articles were included in the meta-analysis. In our meta-analysis, we found that the sKlotho level in patients with DN was significantly lower than that in patients without DN (SMD: -1.52, 95% CI [-2.24, -0.80]), and it was also significantly lower in the early stage of DN (SMD: -1.65, 95% CI [-2.60, -0.70]).ConclusionsThis systematic review was the first to evaluate the relationship between sKlotho levels and DN. The sKlotho level was significantly lower in the early stages of DN, indicating that sKlotho might be a new biomarker of DN in the future.

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Circulating Levels of Soluble Klotho and Fibroblast Growth Factor 23 in Diabetic Patients and Its Association with Early Nephropathy

Cited by 11 publications

References 23 publications

Genome-wide association study for circulating fibroblast growth factor 21 and 23

Genome-wide association study for circulating fibroblast growth factor 21 and 23

The Multiple Roles of Fibroblast Growth Factor in Diabetic Nephropathy

Relationship of Soluble Klotho and Early Stage of Diabetic Nephropathy: A Systematic Review and Meta-Analysis

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