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Circulating α-klotho levels in CKD and relationship to progression

 Hyoung Rae Kim  ;  Bo Young Nam  ;  Dong Wook Kim  ;  Min Woong Kang  ;  Jae-Hyun Han  ;  Mi Jung Lee  ;  Dong Ho Shin  ;  Fa Mee Doh  ;  Hyang Mo Koo  ;  Kwang Il Ko  ;  Chan Ho Kim  ;  Hyung Jung Oh  ;  Tae-Hyun Yoo  ;  Shin-Wook Kang  ;  Dae Suk Han  ;  Seung Hyeok Han 
 American Journal of Kidney Diseases, Vol.61(6) : 899-909, 2013 
Journal Title
 American Journal of Kidney Diseases 
Issue Date
BACKGROUND: α-Klotho is reported to have protective effects against kidney injury, and its renal expression is decreased in many experimental models of kidney disease. However, circulating α-klotho levels in human chronic kidney disease (CKD) and the relationship to progression are unknown. STUDY DESIGN: Post hoc analysis of a prospective cohort study. SETTING & PARTICIPANTS: 243 of 301 participants from a CKD cohort at our institution between January 2006 and December 2011 were eligible for the study. PREDICTOR: Baseline α-klotho levels. OUTCOMES: Primary outcome was the composite of doubling of baseline serum creatinine concentration, end-stage renal disease, or death. End-stage renal disease was defined as onset of treatment by renal replacement therapy. MEASUREMENTS: Serum α-klotho and fibroblast growth factor 23 (FGF-23) were measured using enzyme-linked immunosorbent assay. RESULTS: Lower serum α-klotho levels were associated with more severe CKD stage in the cross-sectional analysis of the baseline data (P for trend < 0.001). In the adjusted multivariable linear regression model, log(α-klotho) was associated independently with estimated glomerular filtration rate (β = 0.154; P = 0.001). Cox regression analysis showed that baseline α-klotho level independently predicted the composite outcome after adjustment for age, diabetes, blood pressure, estimated glomerular filtration rate, proteinuria, parathyroid hormone level, and FGF-23 level (HR per 10-pg/mL increase, 0.96; 95% CI, 0.94-0.98; P < 0.001). When patients were categorized into 2 groups according to baseline median α-klotho value, 43 (35.2%) patients with α-klotho levels ≤396.3 pg/mL reached the primary composite outcome compared with 19 (15.7%) with α-klotho levels >396.3 pg/mL (HR, 2.03; 95% CI, 1.07-3.85; P = 0.03). LIMITATIONS: Uncontrolled dietary phosphorus intake and use of frozen samples. CONCLUSIONS: This observational study showed that low circulating α-klotho levels were associated with adverse kidney disease outcome, suggesting that α-klotho is a novel biomarker for CKD progression. More data from larger prospective longitudinal studies are required to validate our findings
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1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원)
Yonsei Authors
강민웅(Kang, Min Woong)
강신욱(Kang, Shin Wook) ORCID logo https://orcid.org/0000-0002-5677-4756
고광일(Ko, Kwang Il)
구향모(Koo, Hyang Mo)
김동욱(Kim, Dong Wook)
김찬호(Kim, Chan Ho)
김형래(Kim, Hyoung Rae)
남보영(Nam, Bo Young)
도화미(Doh, Fa Mee) ORCID logo https://orcid.org/0000-0002-4780-6728
오형중(Oh, Hyung Jung)
유태현(Yoo, Tae Hyun) ORCID logo https://orcid.org/0000-0002-9183-4507
이미정(Lee, Mi Jung)
한대석(Han, Dae Suk)
한승혁(Han, Seung Hyeok) ORCID logo https://orcid.org/0000-0001-7923-5635
한재현(Han, Jae Hyun)
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