Dataset Information

Low Klotho/Fibroblast Growth Factor 23 Ratio Is an Independent Risk Factor for Renal Progression in Chronic Kidney Disease: Finding From KNOW-CKD.

ABSTRACT:

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.

SUBMITTER: Kim HJ

PROVIDER: S-EPMC9304693 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Low Klotho/Fibroblast Growth Factor 23 Ratio Is an Independent Risk Factor for Renal Progression in Chronic Kidney Disease: Finding From KNOW-CKD.

Kim Hyo Jin HJ Kim Yunmi Y Kang Minjung M Kim Seonmi S Park Sue Kyung SK Sung Suah S Hyun Young Youl YY Jung Ji Yong JY Ahn Curie C Oh Kook-Hwan KH

Frontiers in medicine 20220708

<h4>Background</h4>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).<h4>Methods</h4>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). Par ...[more]

PMID: 35872753

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Project description:Background and objectivesEpidemiologic studies suggest that higher serum phosphaturic hormone fibroblast growth factor 23 levels are associated with increase morbidity and mortality. The aim of the FGF23 Reduction Efficacy of a New Phosphate Binder in CKD Trial was to evaluate the effect of sevelamer carbonate on serum C-terminal fibroblast growth factor 23 levels in normophosphatemic patients with CKD stage 3b/4.Design, setting, participants, & measurementsPatients with CKD, eGFR between 45 and 15 ml/min per 1.73 m2, fasting serum phosphate concentration >3.1 mg/dl, and serum C-terminal fibroblast growth factor 23 >80 relative units/ml were included in our double-blind, placebo-controlled, randomized multicenter study. All patients received 100,000 IU cholecalciferol at time of randomization. Participants received either placebo or sevelamer carbonate 4.8 g daily during a 12-week period. Biologic parameters, including serum C-terminal fibroblast growth factor 23, intact fibroblast growth factor 23, and α-klotho, were evaluated at baseline and 12 weeks after inclusion.ResultsOf 96 screened patients, 78 (mean±SD age: 63±13 years old; 70% men; mean eGFR: 27±9 ml/min per 1.73 m2) met the inclusion criteria. At baseline, mean eGFR was 27±9 ml/min per 1.73 m2, mean serum phosphate level was 3.8±0.5 mg/dl, and median (interquartile range) serum C-terminal fibroblast growth factor 23 level was 157 (120-241) relative units/ml. After 12 weeks of treatment, urinary phosphate-to-creatinine ratio fell significantly in the sevelamer group. The sevelamer and placebo groups did not differ significantly in terms of median change in serum C-terminal fibroblast growth factor 23 levels: the median (interquartile range) change was 38 (-13-114) relative units/ml in the placebo group and 37 (-1-101) relative units/ml in the sevelamer group (P=0.77). There was no significant difference in serum intact fibroblast growth factor 23, α-klotho, or phosphate levels changes between the two groups. Serum total and LDL cholesterol levels fell significantly in the sevelamer group.ConclusionsIn our double-blind, placebo-controlled, randomized study performed in normophosphatemic patients with CKD, a 12-week course of sevelamer carbonate significantly reduced phosphaturia without changing serum phosphorus but did not significantly modify serum C-terminal fibroblast growth factor 23 and intact fibroblast growth factor 23 or α-klotho levels.

Project description:Background and objectivesHigh levels of fibroblast growth factor 23 are associated with accelerated progression of CKD. Whether high fibroblast growth factor 23 levels also predict incident CKD is uncertain.Design, setting, participants, & measurementsA prospective case-cohort study was conducted within the Action to Control Cardiovascular Risk in Diabetes Trial. The analytic sample consisted of a random subcohort of 590 patients with type 2 diabetes without prevalent CKD at baseline, 124 of whom developed incident CKD during follow-up, and 520 additional patients with incident CKD outside the random subcohort. The association between serum intact fibroblast growth factor 23 and incident CKD, defined as the new onset of eGFR<60 ml/min per 1.73 m(2) that represented a ≥25% decrease from baseline in an individual with eGFR≥60 ml/min per 1.73 m(2) and no microalbuminuria (<30 mg/g creatinine) at baseline, was tested.ResultsThe mean baseline eGFR in the random subcohort was 90.9±22.7 ml/min per 1.73 m(2). During a median follow-up of 4.7 years, there was a total of 644 patients with incident CKD. The median baseline fibroblast growth factor 23 level was modestly higher among patients with incident CKD versus controls (43.5, interquartile range=34.7-55.1 versus 39.8, interquartile range=31.9-49.5 pg/ml; P<0.001). Higher baseline fibroblast growth factor 23 levels were associated with higher risk of incident CKD in unadjusted and demographics-adjusted models, but the effect was attenuated after additional adjustment for clinical risk factors and baseline eGFR (hazard ratio per SD of natural log fibroblast growth factor 23, 1.09; 95% confidence interval, 0.94 to 1.27), which was the strongest predictor of incident CKD. Consistent with the results of primary analyses, baseline fibroblast growth factor 23 was not associated with eGFR slope.ConclusionsHigher fibroblast growth factor 23 levels are not independently associated with higher risk of incident CKD in patients with type 2 diabetes.

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Dataset Information

Low Klotho/Fibroblast Growth Factor 23 Ratio Is an Independent Risk Factor for Renal Progression in Chronic Kidney Disease: Finding From KNOW-CKD.

Background

Methods

Results

Conclusions

Publications

Low Klotho/Fibroblast Growth Factor 23 Ratio Is an Independent Risk Factor for Renal Progression in Chronic Kidney Disease: Finding From KNOW-CKD.

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