FGF23 and Klotho in relation to markers of endothelial dysfunction in kidney transplant recipients.
BACKGROUND
Fibroblast growth factor (FGF) 23 is a newly discovered member of the FGF family. Klotho is a cofactor of FGF23. Activation of the FGF23-Klotho system is responsible for negative phosphate balance. In addition, FGF23 appears to be a risk factor for cardiovascular complications. The aim of this study was to assess levels of FGF23 and Klotho in stable kidney transplant recipients on triple immunosuppressive therapy in relation to comorbidities and markers endothelial dysfunction. Healthy volunteers served as a control group.


METHODS
Hemoglobin, urea, and creatinine were studied with the use of standard laboratory methods in the hospital central laboratory. We assessed FGF23 and Klotho, markers of endothelial function/injury von Willebrand factor (vWF), intercellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), and interleukin (IL) 6, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and copeptin with the use of commercially available assays.


RESULTS
FGF23 was significantly higher and Klotho significantly lower in kidney transplant recipients compared with healthy volunteers. FGF23 correlated with copeptin (r = 0.28; P < .05), IL-6 (r = 0.39; P < .01), VCAM (r = 0.36; P < .01), time after transplantation (r = 0.31; P < .05), platelet count (r = 0.31; P < .05), mean corpuscular volume (r = -0.40; P < .01), and phosphate (r = 0.31; P < .05). Klotho correlated with NT-proBNP (r = 0.38; P < .01), vWF (r = -0.26; P < .05), calcium (r = -0.39; P < .01), and age (r = 0.45; P < .001). FGF23 was significantly higher and Klotho significantly lower in patients with estimated glomerular filtration rate (eGFR) >60 mL/min compared with patients with eGFR <60 mL/min.


CONCLUSIONS
Disturbances in the FGF23-Klotho system appeared to be related to the endothelial cell injury. Thus they are involved not only in pathogenesis of the metabolic bone disease but also in cardiovascular complications, particularly in kidney disease.
2nd Department of Nephrology, Medical University, Bialystok, Poland. Electronic address: jolmal@poczta.onet.pl.
Jolanta
J
Malyszko
2nd Department of Nephrology, Medical University, Bialystok, Poland.
E
E
Koc-Zorawska
Department of Nephrology, Internal Medicine and Dialysis Therapy, Medical University, Warsaw, Poland.
J
J
Matuszkiewicz-Rowinska
2nd Department of Nephrology, Medical University, Bialystok, Poland.
Jacek
J
Malyszko
D000328:Adult; D015415:Biomarkers / Q000097:blood; D042783:Endothelial Cells; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood* / Q000502:physiology; D005966:Glucuronidase / Q000097:blood* / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007668:Kidney / Q000503:physiopathology; D007674:Kidney Diseases / Q000503:physiopathology; D016030:Kidney Transplantation; D000090265:Klotho Proteins; D008297:Male; D008875:Middle Aged; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000502:physiology; D066027:Transplant Recipients; D014652:Vascular Diseases / Q000503:physiopathology
D015415:Biomarkers; C000717427:FGF23 protein, human; D007166:Immunosuppressive Agents; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D051496:Receptor, Fibroblast Growth Factor, Type 1; D005966:Glucuronidase; D000090265:Klotho Proteins