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, TaeHyun Yoo, Shin-Wook Kang, Dae Suk Han, SeungHyeok Han

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)899-909
Number of pages11
JournalAmerican Journal of Kidney Diseases
Volume61
Issue number6
DOIs
Publication statusPublished - 2013 Jun 1

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Chronic Renal Insufficiency
Kidney Diseases
Chronic Kidney Failure
Dietary Phosphorus
Serum
Prospective Studies
Kidney
Renal Replacement Therapy
Observational Studies
Longitudinal Studies
Disease Progression
Creatinine
Cohort Studies
Theoretical Models
Cross-Sectional Studies
Biomarkers
Enzyme-Linked Immunosorbent Assay
Wounds and Injuries
Therapeutics

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Kim, Hyoung Rae ; Nam, Bo Young ; Kim, Dong Wook ; Kang, Min Woong ; Han, Jae Hyun ; Lee, Mi Jung ; Shin, Dong Ho ; Doh, Fa Mee ; Koo, Hyang Mo ; Ko, Kwang Il ; Kim, Chan Ho ; Oh, Hyung Jung ; Yoo, TaeHyun ; Kang, Shin-Wook ; Han, Dae Suk ; Han, SeungHyeok. / Circulating α-klotho levels in CKD and relationship to progression. In: American Journal of Kidney Diseases. 2013 ; Vol. 61, No. 6. pp. 899-909.
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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.",
author = "Kim, {Hyoung Rae} and Nam, {Bo Young} and Kim, {Dong Wook} and Kang, {Min Woong} and Han, {Jae Hyun} and Lee, {Mi Jung} and Shin, {Dong Ho} and Doh, {Fa Mee} and Koo, {Hyang Mo} and Ko, {Kwang Il} and Kim, {Chan Ho} and Oh, {Hyung Jung} and TaeHyun Yoo and Shin-Wook Kang and Han, {Dae Suk} and SeungHyeok Han",
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Kim, HR, Nam, BY, Kim, DW, Kang, MW, Han, JH, Lee, MJ, Shin, DH, Doh, FM, Koo, HM, Ko, KI, Kim, CH, Oh, HJ, Yoo, T, Kang, S-W, Han, DS & Han, S 2013, 'Circulating α-klotho levels in CKD and relationship to progression', American Journal of Kidney Diseases, vol. 61, no. 6, pp. 899-909. https://doi.org/10.1053/j.ajkd.2013.01.024

Circulating α-klotho levels in CKD and relationship to progression. / Kim, Hyoung Rae; Nam, Bo Young; Kim, Dong Wook; Kang, Min Woong; Han, Jae Hyun; Lee, Mi Jung; Shin, Dong Ho; Doh, Fa Mee; Koo, Hyang Mo; Ko, Kwang Il; Kim, Chan Ho; Oh, Hyung Jung; Yoo, TaeHyun; Kang, Shin-Wook; Han, Dae Suk; Han, SeungHyeok.

In: American Journal of Kidney Diseases, Vol. 61, No. 6, 01.06.2013, p. 899-909.

Research output: Contribution to journalArticle

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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, TaeHyun

AU - Kang, Shin-Wook

AU - Han, Dae Suk

AU - Han, SeungHyeok

PY - 2013/6/1

Y1 - 2013/6/1

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.

AB - 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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