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Low Klotho/Fibroblast Growth Factor 23 Ratio Is an Independent Risk Factor for Renal Progression in Chronic Kidney
Hyo Jin Kim1,2, Yunmi Kim3, Minjung Kang4
1Department of Internal Medicine, Pusan National University School of Medicine, Busan, South Korea.
Insights
A low Klotho/FGF23 ratio is linked to a higher risk of kidney disease progression in predialysis patients. This ratio did not predict cardiovascular events or mortality in the study cohort.
Area of Science:
- Nephrology
- Endocrinology
- Cardiology
Background:
- Chronic kidney disease (CKD) is a global health concern.
- Klotho and fibroblast growth factor 23 (FGF23) are key regulators of mineral and bone metabolism.
- The ratio of soluble Klotho to FGF23 (Klotho/FGF23) may offer insights into CKD progression and related complications.
Purpose of the Study:
- To investigate the association between the Klotho/FGF23 ratio and renal progression in patients with predialysis CKD.
- To evaluate the Klotho/FGF23 ratio as a predictor of cardiovascular events and mortality in this patient population.
Main Methods:
- A cohort of 2,099 predialysis CKD patients had their soluble Klotho and C-terminal FGF23 levels measured.
- The Klotho/FGF23 ratio was calculated and participants were divided into quartiles.
- Renal events, cardiovascular events, and mortality were tracked over a mean follow-up of 64 months.
Main Results:
- The lowest two quartiles of the Klotho/FGF23 ratio were associated with a significantly increased risk of renal events (HR: 1.36-1.45).
- No significant association was found between the Klotho/FGF23 ratio and the composite outcome of cardiovascular events and death.
- Higher prevalence of left ventricular hypertrophy and vascular calcification was observed in lower Klotho/FGF23 ratio groups.
Conclusions:
- A low Klotho/FGF23 ratio is a significant risk factor for renal events in Korean predialysis CKD patients.
- The Klotho/FGF23 ratio may serve as a valuable biomarker for predicting renal disease progression in CKD.
Background:
We aimed to evaluate soluble Klotho and circulating fibroblast growth factor 23 (FGF23) ratio as a risk factor for renal progression, cardiovascular (CV) events, and mortality in chronic kidney disease (CKD).
Methods:
We analyzed 2,099 subjects from a CKD cohort whose soluble Klotho and C-terminal FGF23 levels were measured at enrollment. The Klotho to FGF23 ratio was calculated as Klotho values divided by FGF23 values + 1 (hereinafter called the Klotho/FGF23 ratio). Participants were categorized into quartiles according to Klotho/FGF23 ratio. The primary outcome was renal events, defined as the doubling of serum creatinine, 50% reduction of estimated glomerular filtration rate from the baseline values, or development of end-stage kidney disease. The secondary outcomes consisted of CV events and death. Changes in CV parameters at the time of enrollment and during follow-up according to the Klotho/FGF23 ratio were also examined.
Results:
During the follow-up period of 64.0 ± 28.2 months, 735 (35.1%) and 273 (13.0%) subjects developed renal events and composite outcomes of CV events and death, respectively. After adjustment, the first (HR: 1.36; 95% CI: 1.08-1.72, P = 0.010) and second (HR: 1.45; 95% CI: 1.15-1.83, P = 0.002) quartiles with regard to the Klotho/FGF23 ratio showed elevated risk of renal events as compared to the fourth quartile group. There was no significant association between Klotho/FGF23 ratio and the composite outcome of CV events and death. The prevalence of left ventricular hypertrophy and vascular calcification was higher in the low Klotho/FGF23 ratio quartiles at baseline and at the fourth-year follow-up.
Conclusions:
Low Klotho/FGF23 ratio was significantly associated with increased renal events in the cohort of Korean predialysis CKD patients.
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