Association of FGF19, FGF21 and FGF23 with carbohydrate metabolism parameters and insulin resistance in patients with chronic kidney disease

Insulin resistance (IR) is characterised by increased gluconeogenesis in the liver and the resistance of peripheral receptors to insulin. Several factors, including IR, type 2 diabetes, new-onset diabetes after transplant (NODAT) and secondary parathyroidism, are related to chronic kidney disease (CKD). These factors are associated with higher mortality due to the increased risk of cardiovascular complications. Many factors have been identified as potential markers of IR in CKD. These factors include fibroblast growth factors (FGFs), a subfamily of endocrine polypeptides. In this study, we examined the association of FGF19, FGF21 and FGF23 with selected parameters related to carbohydrate metabolism and insulin resistance in non diabetic patients with predialysis CKD and in non diabetic patients after renal transplantation. The study included 108 non diabetic subjects: 40 patients with predialysis CKD, 45 patients with CKD who had undergone renal transplantation, and 23 healthy subjects (control group). In patients who had undergone renal transplantation, concentrations of FGF23 were increased compared to the control group and patients with predialysis CKD. The highest and lowest FGF19 concentrations were observed in CKD patients and in patients who had undergone kidney transplantation, respectively. This difference was statistically significant. Leptin concentrations were higher in CKD patients compared to the control group and patients who had undergone kidney transplantation. There were no statistically significant differences in adiponectin concentrations, lean body mass or fat tissue mass between the studied groups. HOMA-IR and insulin levels were significantly increased in CKD patients and in patients who had undergone renal transplantation in comparison to the control group. The results of the study suggest the involvement of FGF in carbohydrate metabolism and insulin resistance in patients with predialysis CKD, as well as a correlation with kidney function.

[1]  L. Domański,et al.  Bone metabolism parameters in hemodialysis patients with chronic kidney disease and in patients after kidney transplantation. , 2019, Physiological research.

[2]  K. Safranow,et al.  Chronic Kidney Disease Is Associated with Increased Plasma Levels of Fibroblast Growth Factors 19 and 21 , 2019, Kidney and Blood Pressure Research.

[3]  O. Moe,et al.  Fibroblast growth factor 21 in chronic kidney disease , 2018, Journal of Nephrology.

[4]  H. Kayabaşı,et al.  Is FGF23 effective on insulin resistance in individuals with metabolic syndrome? , 2018, Hormone molecular biology and clinical investigation.

[5]  Xiaokun Li,et al.  FGF Family: From Drug Development to Clinical Application , 2018, International journal of molecular sciences.

[6]  A. Heikal,et al.  Fibroblast growth factor-23 is a strong predictor of insulin resistance among chronic kidney disease patients , 2018, Renal failure.

[7]  N. Chattipakorn,et al.  Increased plasma FGF21 level as an early biomarker for insulin resistance and metabolic disturbance in obese insulin-resistant rats , 2018, Diabetes & vascular disease research.

[8]  M. Pencina,et al.  Longitudinal FGF23 Trajectories and Mortality in Patients with CKD. , 2017, Journal of the American Society of Nephrology : JASN.

[9]  K. Rye,et al.  Fibroblast growth factor 21 in chronic kidney disease. , 2017, Clinica chimica acta; international journal of clinical chemistry.

[10]  Y. Bao,et al.  Association of serum fibroblast growth factor 19 levels with visceral fat accumulation is independent of glucose tolerance status. , 2017, Nutrition, metabolism, and cardiovascular diseases : NMCD.

[11]  M. Strowski.  Impact of FGF21 on glycemic control , 2017, Hormone molecular biology and clinical investigation.

[12]  B. Kestenbaum,et al.  Fibroblast Growth Factor 23, Mineral Metabolism, and Adiposity in Normal Kidney Function , 2017, The Journal of clinical endocrinology and metabolism.

[13]  C. Zoccali,et al.  Insulin resistance in chronic kidney disease: a systematic review. , 2016, American journal of physiology. Renal physiology.

[14]  F. Jornayvaz,et al.  Leptin as a Potential Regulator of FGF21 , 2016, Cellular Physiology and Biochemistry.

[15]  B. Owen,et al.  Metabolic roles of endocrine fibroblast growth factors. , 2015, Current opinion in pharmacology.

[16]  A. Moschetta,et al.  Therapeutic potential of the endocrine fibroblast growth factors FGF19, FGF21 and FGF23 , 2015, Nature Reviews Drug Discovery.

[17]  Xiaokun Li,et al.  Minireview: Roles of Fibroblast Growth Factors 19 and 21 in Metabolic Regulation and Chronic Diseases. , 2015, Molecular endocrinology.

[18]  S. Kliewer,et al.  Bile Acids as Hormones: The FXR-FGF15/19 Pathway , 2015, Digestive Diseases.

[19]  S. Judd,et al.  Associations of Fibroblast Growth Factor-23 with Markers of Inflammation, Insulin Resistance and Obesity in Adults , 2015, PloS one.

[20]  H. Fu,et al.  The effects of LY2405319, an FGF21 analog, in obese human subjects with type 2 diabetes. , 2013, Cell metabolism.

[21]  S. Bornstein,et al.  Adiponectin mediates the metabolic effects of FGF21 on glucose homeostasis and insulin sensitivity in mice. , 2013, Cell metabolism.

[22]  D. Drożdż,et al.  FGF23 contributes to insulin sensitivity in obese adolescents – preliminary results , 2012, Clinical endocrinology.

[23]  Jian Xiao,et al.  Serum Levels of FGF-21 Are Increased in Coronary Heart Disease Patients and Are Independently Associated with Adverse Lipid Profile , 2010, PloS one.

[24]  K. Park,et al.  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. , 2010, Metabolism: clinical and experimental.

[25]  H. Colak,et al.  Relationship of insulin resistance in chronic haemodialysis patients with inflammatory indicators, malnutrition, echocardiographic parameters and 24 hour ambulatory blood pressure monitoring , 2010, Scandinavian journal of urology and nephrology.

[26]  M. Fasshauer,et al.  Fibroblast Growth Factor 19 Serum Levels: Relation to Renal Function and Metabolic Parameters , 2009, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[27]  M. Matoulek,et al.  Serum concentrations and tissue expression of a novel endocrine regulator fibroblast growth factor‐21 in patients with type 2 diabetes and obesity , 2009, Clinical endocrinology.

[28]  A. Shanafelt,et al.  FGF21: a novel prospect for the treatment of metabolic diseases. , 2009, Current opinion in investigational drugs.

[29]  M. Fasshauer,et al.  Serum Levels of the Adipokine FGF21 Depend on Renal Function , 2009, Diabetes Care.

[30]  D. Moller,et al.  Fibroblast growth factor 21 corrects obesity in mice. , 2008, Endocrinology.

[31]  S. Fukumoto.  Actions and mode of actions of FGF19 subfamily members. , 2008, Endocrine journal.

[32]  L. Quarles,et al.  How fibroblast growth factor 23 works. , 2007, Journal of the American Society of Nephrology : JASN.

[33]  A. Åsberg,et al.  Association between insulin resistance and endothelial dysfunction in renal transplant recipients , 2006, Clinical transplantation.

[34]  D. French,et al.  Printed in U.S.A. Copyright © 2002 by The Endocrine Society Transgenic Mice Expressing Human Fibroblast Growth Factor-19 Display Increased Metabolic Rate and Decreased Adiposity , 2022 .

[35]  M. Konishi,et al.  Identification of a novel FGF, FGF-21, preferentially expressed in the liver. , 2000, Biochimica et biophysica acta.

[36]  G. Pacini,et al.  Insulin resistance and hyperinsulinemia are already present in patients with incipient renal disease. , 1998, Kidney international.

[37]  R. Ross,et al.  Insulin resistance is associated with Fibroblast Growth Factor-23 in stage 3-5 chronic kidney disease patients. , 2014, Journal of diabetes and its complications.

[38]  한대석,et al.  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 , 2010 .