Plasma s-Klotho is related to kidney function and predicts adverse renal outcomes in patients with advanced chronic kidney disease

J Investig Med. 2018 Mar;66(3):669-675. doi: 10.1136/jim-2017-000560. Epub 2017 Oct 23.

Abstract

To investigate whether the soluble Klotho (s-Klotho) level in patients with chronic kidney disease (CKD) is related to kidney function and whether a low s-Klotho level can predict adverse renal outcomes or CKD progression in patients with advanced CKD. 112 patients with CKD stages 3-5 and 30 healthy volunteers were enrolled. Blood samples were collected to measure serum creatinine, calcium, phosphorus, intact parathyroid hormone, and hemoglobin. s-Klotho and fibroblast growth factor 23 (FGF23) were determined by ELISA. We first conducted a cross-sectional study to investigate correlations between s-Klotho and estimated glomerular filtration rate (eGFR) and other parameters. Patients were then followed prospectively for 20.1±10.1 months according to s-Klotho median level until serum creatinine doubled, or initiation of renal replacement therapy, or death. s-Klotho levels inpatients with CKD were significantly lower than that in the control group. For patients with CKD, there were no differences in age distribution among subgroups. However, s-Klotho level differed significantly across CKD stages, and it was lower in the advanced CKD group compared with the moderate CKD group. Correlation analysis revealed that s-Klotho was positively associated with eGFR, but inversely associated with FGF23. During the follow-up of 20.1±10.1 months, patients with higher s-Klotho levels showed a reduced risk of kidney adverse outcomes, including serum creatinine doubling and initiation of renal replacement therapy. Cox regression analysis revealed that low s-Klotho was an independent risk factor for CKD progression. s-Klotho level was closely correlated with kidney function, further, low s-Klotho level could predict adverse kidney disease outcomes in patients with progressive CKD.

Keywords: chronic; kidney diseases; kidney failure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Demography
  • Female
  • Fibroblast Growth Factor-23
  • Glomerular Filtration Rate
  • Glucuronidase / blood*
  • Humans
  • Kaplan-Meier Estimate
  • Kidney / physiopathology*
  • Klotho Proteins
  • Linear Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Proportional Hazards Models
  • Renal Insufficiency, Chronic / blood*
  • Renal Insufficiency, Chronic / physiopathology*
  • Solubility
  • Treatment Outcome

Substances

  • FGF23 protein, human
  • Fibroblast Growth Factor-23
  • Glucuronidase
  • Klotho Proteins