Klotho variants and chronic hemodialysis mortality

David J. Friedman, Maryam Afkarian, Hector Tamez, Ishir Bhan, Tamara Isakova, Myles Wolf, Elizabeth Ankers, Jun Ye, Marcello Tonelli, Carmine Zoccali, Makoto Kuro-o, Orson Moe, S. Ananth Karumanchi, Ravi Thadhani

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Patients with end-stage renal disease (ESRD) suffer exceptionally high mortality rates in their first year of chronic hemodialysis. Both vitamin D and fibroblast growth factor (FGF)-23 levels correlate with survival in these patients. Klotho is a protein in the vitamin D/FGF-23 signaling pathway that has been linked with accelerated aging and early mortality in animal models. We therefore hypothesized that genetic variation in the Klotho gene might be associated with survival in subjects with ESRD. We tested the association between 12 single nucleotide polymorphisms (SNPs) in the Klotho gene and mortality in a cohort of ESRD patients during their first year on hemodialysis (n = 1307 white and Asian). We found a significant association between the CC genotype of one tag SNP, rs577912, and increased risk for 1-yr mortality (RR, 1.76; 95% CI, 1.19-2.59; p = 0.003). This effect was even more marked among patients who were not treated with activated vitamin D supplementation (HR, 2.51; 95% CI, 1.18-5.34; p = 0.005). In lymphoblastoid cell lines derived from HapMap subjects, the CC genotype was associated with a 16-21% lower Klotho expression compared with the AA/AC genotype. Our data suggest that a specific Klotho variant (rs577912) is linked to survival in ESRD patients initiating chronic hemodialysis and that therapy with activated vitamin D may modify this risk.

Original languageEnglish (US)
Pages (from-to)1847-1855
Number of pages9
JournalJournal of Bone and Mineral Research
Volume24
Issue number11
DOIs
StatePublished - Nov 2009

Fingerprint

Renal Dialysis
Vitamin D
Chronic Kidney Failure
Mortality
Genotype
Single Nucleotide Polymorphism
Survival
HapMap Project
Genes
Animal Models
Cell Line
Proteins
fibroblast growth factor 23
Therapeutics

Keywords

  • End-stage renal disease
  • Fibroblast growth factor-23
  • HapMap
  • Hemodialysis
  • Klotho
  • Mortality
  • Polymorphism
  • Vitamin D

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

Cite this

Friedman, D. J., Afkarian, M., Tamez, H., Bhan, I., Isakova, T., Wolf, M., ... Thadhani, R. (2009). Klotho variants and chronic hemodialysis mortality. Journal of Bone and Mineral Research, 24(11), 1847-1855. https://doi.org/10.1359/jbmr.090516

Klotho variants and chronic hemodialysis mortality. / Friedman, David J.; Afkarian, Maryam; Tamez, Hector; Bhan, Ishir; Isakova, Tamara; Wolf, Myles; Ankers, Elizabeth; Ye, Jun; Tonelli, Marcello; Zoccali, Carmine; Kuro-o, Makoto; Moe, Orson; Karumanchi, S. Ananth; Thadhani, Ravi.

In: Journal of Bone and Mineral Research, Vol. 24, No. 11, 11.2009, p. 1847-1855.

Research output: Contribution to journalArticle

Friedman, DJ, Afkarian, M, Tamez, H, Bhan, I, Isakova, T, Wolf, M, Ankers, E, Ye, J, Tonelli, M, Zoccali, C, Kuro-o, M, Moe, O, Karumanchi, SA & Thadhani, R 2009, 'Klotho variants and chronic hemodialysis mortality', Journal of Bone and Mineral Research, vol. 24, no. 11, pp. 1847-1855. https://doi.org/10.1359/jbmr.090516
Friedman DJ, Afkarian M, Tamez H, Bhan I, Isakova T, Wolf M et al. Klotho variants and chronic hemodialysis mortality. Journal of Bone and Mineral Research. 2009 Nov;24(11):1847-1855. https://doi.org/10.1359/jbmr.090516
Friedman, David J. ; Afkarian, Maryam ; Tamez, Hector ; Bhan, Ishir ; Isakova, Tamara ; Wolf, Myles ; Ankers, Elizabeth ; Ye, Jun ; Tonelli, Marcello ; Zoccali, Carmine ; Kuro-o, Makoto ; Moe, Orson ; Karumanchi, S. Ananth ; Thadhani, Ravi. / Klotho variants and chronic hemodialysis mortality. In: Journal of Bone and Mineral Research. 2009 ; Vol. 24, No. 11. pp. 1847-1855.
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