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Circulating α-klotho levels in CKD and relationship to progression

Title
Circulating α-klotho levels in CKD and relationship to progression
Authors
Hyoung Rae Kim;Bo Young Nam;Seung Hyeok Han;Dae Suk Han;Shin-Wook Kang;Tae-Hyun Yoo;Hyung Jung Oh;Chan Ho Kim;Kwang Il Ko;Hyang Mo Koo;Fa Mee Doh;Dong Ho Shin;Mi Jung Lee;Jae-Hyun Han;Min Woong Kang;Dong Wook Kim
Issue Date
2013
Journal Title
American Journal of Kidney Diseases
ISSN
0272-6386
Citation
American Journal of Kidney Diseases, Vol.61(6) : 899~909, 2013
Abstract
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
URI
http://www.sciencedirect.com/science/article/pii/S0272638613004794

http://ir.ymlib.yonsei.ac.kr/handle/22282913/86823
DOI
10.1053/j.ajkd.2013.01.024
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Internal Medicine
1. 연구논문 > 1. College of Medicine > Yonsei Biomedical Research Center
Yonsei Authors
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