Circulating α-klotho levels in CKD and relationship to progression.

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: 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
• Journal: American journal of kidney diseases : the official journal of the National Kidney Foundation (Am J Kidney Dis) Vol. 61 Issue 6 Pg. 899-909 (Jun 2013) ISSN: 1523-6838 [Electronic] United States
• PMID: 23540260 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers
• FGF23 protein, human
• Fibroblast Growth Factors
• Fibroblast Growth Factor-23
• Creatinine
• Glucuronidase
• Klotho Proteins

Topics

• Adult
• Aged
• Biomarkers (blood)
• Cohort Studies
• Creatinine (blood)
• Cross-Sectional Studies
• Disease Progression
• Enzyme-Linked Immunosorbent Assay
• Female
• Fibroblast Growth Factor-23
• Fibroblast Growth Factors (blood)
• Glomerular Filtration Rate
• Glucuronidase (blood)
• Humans
• Kidney Failure, Chronic (blood)
• Klotho Proteins
• Linear Models
• Male
• Middle Aged
• Prognosis
• Proportional Hazards Models
• Prospective Studies
• Renal Insufficiency, Chronic (blood)
• Young Adult