Plasma Klotho is not related to kidney function and does not predict adverse outcome in patients with chronic kidney disease.
A decreased expression of the fibroblast growth factor (FGF)-23 coreceptor Klotho was postulated as an early alteration in chronic kidney disease mineral and bone disorder, resulting in a compensatory increase in plasma FGF-23 levels. Klotho exists in both membrane-bound and secreted (sKlotho) forms, the latter of which may exert vasculoprotective effects. Here we analyzed plasma sKlotho levels in a large cohort of 312 patients with stage 2-4 chronic kidney disease, and assessed plasma levels of FGF-23, sKlotho, parathyroid hormone, and urinary fractional phosphate excretion. Patients were prospectively followed for an average of 2.2 years for the occurrence of death or initiation of renal replacement therapy. The levels of sKlotho were significantly associated with age, but not with the glomerular filtration rate or other parameters of calcium-phosphate metabolism. Moreover, while patients with high FGF-23 levels faced worst outcome even after adjustment for confounders, we found no prognostic impact of sKlotho. Thus, plasma levels of sKlotho were not related to kidney function and did not predict adverse outcome in patients with chronic kidney disease. Future studies are needed to understand how tissue expression, urinary excretion, and plasma levels of Klotho diverge in progressive chronic kidney disease.
Department of Internal Medicine IV - Nephrology and Hypertension, Saarland University Hospital, Homburg/Saar, Germany.
Sarah
S
Seiler
Ming
M
Wen
Heinz J
HJ
Roth
Michael
M
Fehrenz
Franziska
F
Flügge
Esther
E
Herath
Anja
A
Weihrauch
Danilo
D
Fliser
Gunnar H
GH
Heine
D000368:Aged; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood; D005500:Follow-Up Studies; D005966:Glucuronidase / Q000097:blood*; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D000090265:Klotho Proteins; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000175:diagnosis* / Q000401:mortality; D017582:Renal Replacement Therapy; D012720:Severity of Illness Index; D015996:Survival Rate
D015415:Biomarkers; C000717427:FGF23 protein, human; D010281:Parathyroid Hormone; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins