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Circulating α-klotho levels in CKD and relationship to progression
Hyoung Rae Kim1, Bo Young Nam, Dong Wook Kim
1Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea.
Insights
Low circulating α-klotho levels are linked to worse outcomes in chronic kidney disease (CKD) patients. This suggests α-klotho may serve as a biomarker for predicting CKD progression and adverse events.
Area of Science:
- Nephrology
- Biomarkers
- Chronic Kidney Disease
Background:
- α-Klotho demonstrates protective effects against kidney injury in experimental models.
- Renal expression of α-Klotho is often reduced in kidney disease.
- Circulating α-Klotho levels and their association with human CKD progression remain unclear.
Purpose of the Study:
- To investigate the relationship between circulating α-Klotho levels and the progression of chronic kidney disease (CKD).
- To determine if α-Klotho serves as a predictive biomarker for adverse outcomes in CKD patients.
Main Methods:
- Post hoc analysis of a prospective cohort study involving 243 participants with CKD.
- Measurement of baseline serum α-Klotho and FGF-23 using enzyme-linked immunosorbent assay.
- Cox regression analysis to assess the association between α-Klotho and composite outcomes (doubling of creatinine, ESRD, or death).
Main Results:
- Lower serum α-Klotho levels correlated with more severe CKD stages.
- Baseline α-Klotho independently predicted adverse kidney disease outcomes, including end-stage renal disease (ESRD) or death.
- Patients with lower α-Klotho levels had a significantly higher risk of reaching the primary composite outcome.
Conclusions:
- Low circulating α-Klotho levels are associated with adverse outcomes in patients with chronic kidney disease.
- α-Klotho may represent a novel biomarker for predicting CKD progression.
- Further validation in larger prospective studies is warranted.
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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