Front Med (Lausanne). 2022;9:904963.

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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제1저자 김효진 · 교신저자 오국환

PMID 35872753 PMC9304693 DOI 10.3389/fmed.2022.904963 IF 3.6 신장내과

소속 (10)

Department of Internal Medicine, Pusan National University School of Medicine, Busan, South Korea.
Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea.
Department of Internal Medicine, Inje University Busan Paik Hospital, Busan, South Korea.
Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.
Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea.
Department of Internal Medicine, Eulji Medical Center, Eulji University, Seoul, South Korea.
Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, South Korea.
Department of Internal Medicine, National Medical Center, Seoul, South Korea.
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.

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.

Keywords

Klothochronic kidney diseasefibroblast growth factor 23mortalityrenal progression

Figures

**Figure 1** Event rates for renal events and composites of death and CV events according to Klotho/FGF23 ratio. The first quartile of the Klotho/FGF23 ratio group was at a greater risk of developing renal events compared to the other quartile groups (P < 0.001). Composites of death and CV events were not significantly different according to Klotho/FGF23 ratio groups (P = 0.153). FGF23, fibroblast growth factor 23; CV, cardiovascular.

**Figure 2** Renal events according to Klotho/FGF23 ratio. The Kaplan-Meier curves show that the low Klotho/FGF23 ratio group had a significantly higher cumulative incidence of renal events (P < 0.001). FGF23, fibroblast growth factor 23.

**Figure 3** The eGFR slope and rapid decline of eGFR according to Klotho/FGF23 ratio. **(A)** The eGFR slope according to Klotho/FGF23 ratio; **(B)** rapid decline of eGFR according to Klotho/FGF23 ratio. The eGFR slope was analyzed in 1,851 patients for whom eGFR was measured more than three times during the follow-up period. The eGFR slope was lower in the low Klotho/FGF23 ratio group (P < 0.001; A). The rapid decline of kidney function was defined as an estimated glomerular filtration rate (eGFR) <-3 ml/min/1.73 m²/year. The proportion of patients exhibiting a rapid decline of eGFR was higher in the first quartile of Klotho/FGF23 ratio group (P < 0.001; B). eGFR, estimated glomerular filtration rate by CKD-EPI creatinine equation; FGF23, fibroblast growth factor 23.

그림 출처: PubMed Central 공개 논문 (PMC9304693)

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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