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Circulating α-klotho levels in CKD and relationship to progression.
Am J Kidney Dis. 2013 Jun; 61(6):899-909.AJ

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.

Authors+Show Affiliations

Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23540260

Citation

Kim, Hyoung Rae, et al. "Circulating Α-klotho Levels in CKD and Relationship to Progression." American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, vol. 61, no. 6, 2013, pp. 899-909.
Kim HR, Nam BY, Kim DW, et al. Circulating α-klotho levels in CKD and relationship to progression. Am J Kidney Dis. 2013;61(6):899-909.
Kim, H. R., Nam, B. Y., Kim, D. W., Kang, M. W., Han, J. H., Lee, M. J., Shin, D. H., Doh, F. M., Koo, H. M., Ko, K. I., Kim, C. H., Oh, H. J., Yoo, T. H., Kang, S. W., Han, D. S., & Han, S. H. (2013). Circulating α-klotho levels in CKD and relationship to progression. American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, 61(6), 899-909. https://doi.org/10.1053/j.ajkd.2013.01.024
Kim HR, et al. Circulating Α-klotho Levels in CKD and Relationship to Progression. Am J Kidney Dis. 2013;61(6):899-909. PubMed PMID: 23540260.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Circulating α-klotho levels in CKD and relationship to progression. AU - Kim,Hyoung Rae, AU - Nam,Bo Young, AU - Kim,Dong Wook, AU - Kang,Min Woong, AU - Han,Jae-Hyun, AU - Lee,Mi Jung, AU - Shin,Dong Ho, AU - Doh,Fa Mee, AU - Koo,Hyang Mo, AU - Ko,Kwang Il, AU - Kim,Chan Ho, AU - Oh,Hyung Jung, AU - Yoo,Tae-Hyun, AU - Kang,Shin-Wook, AU - Han,Dae Suk, AU - Han,Seung Hyeok, Y1 - 2013/03/27/ PY - 2012/08/06/received PY - 2013/01/16/accepted PY - 2013/4/2/entrez PY - 2013/4/2/pubmed PY - 2013/7/10/medline SP - 899 EP - 909 JF - American journal of kidney diseases : the official journal of the National Kidney Foundation JO - Am J Kidney Dis VL - 61 IS - 6 N2 - 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. SN - 1523-6838 UR - https://www.unboundmedicine.com/medline/citation/23540260/Circulating_α_klotho_levels_in_CKD_and_relationship_to_progression_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0272-6386(13)00479-4 DB - PRIME DP - Unbound Medicine ER -