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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
Issue Date
Adult ; Aged ; Biomarkers/blood ; Cohort Studies ; Creatinine/blood ; Cross-Sectional Studies ; Disease Progression ; Enzyme-Linked Immunosorbent Assay ; Female ; Fibroblast Growth Factors/blood ; Glomerular Filtration Rate ; Glucuronidase/blood* ; Humans ; Kidney Failure, Chronic/blood ; Linear Models ; Male ; Middle Aged ; Prognosis ; Proportional Hazards Models ; Prospective Studies ; Renal Insufficiency, Chronic/blood* ; Young Adult
α-Klotho ; fibroblast growth factor 23 (FGF-23) ; chronic kidney disease ; kidney disease outcome
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. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kang, Min Woong(강민웅)
Kang, Shin Wook(강신욱) ORCID logo https://orcid.org/0000-0002-5677-4756
Ko, Kwang Il(고광일)
Koo, Hyang Mo(구향모)
Kim, Dong Wook(김동욱)
Kim, Chan Ho(김찬호)
Kim, Hyoung Rae(김형래)
Nam, Bo Young(남보영)
Doh, Fa Mee(도화미) ORCID logo https://orcid.org/0000-0002-4780-6728
Oh, Hyung Jung(오형중)
Yoo, Tae Hyun(유태현) ORCID logo https://orcid.org/0000-0002-9183-4507
Lee, Mi Jung(이미정)
Han, Dae Suk(한대석)
Han, Seung Hyeok(한승혁) ORCID logo https://orcid.org/0000-0001-7923-5635
Han, Jae Hyun(한재현)
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