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Clinical Significance of Klotho, Fibroblast Growth Factor 23, and Their Ratio for Acute Kidney Injury in Sepsis Patients

Year: 2026

Type: article

Abstract: OBJECTIVE: The sepsis-associated acute kidney injury (SA-AKI) is common in patients with sepsis and associated with poor outcomes, yet serum creatinine and urine output have limited value for early assessment. We examined whether admission Klotho, fibroblast growth factor 23 (FGF23), and the Klotho/FGF23 ratio were associated with SA-AKI and short-term outcomes and compared their discriminative performance. METHODS: We conducted a retrospective cohort study of 320 patients admitted to the intensive care unit (ICU) with Sepsis-3-defined sepsis. SA-AKI (n = 112) was retrospectively identified according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Klotho and FGF23 were measured by enzyme-linked immunosorbent assay in stored serum samples collected within 24 h of ICU admission. Discrimination was assessed by receiver operating characteristic analysis, and adjusted associations were evaluated using multivariable logistic and linear regression. RESULTS: Patients with SA-AKI had lower Klotho, higher FGF23, and a reduced Klotho/FGF23 ratio at admission (all p < 0.001). The ratio showed the highest area under the curve biomarkers for SA-AKI (0.84; 95% confidence interval 0.79-0.88) and remained associated with SA-AKI after multivariable adjustment (odds ratio 2.25; 95% confidence interval 1.46-3.53). The ratio decreased with increasing KDIGO stage. Among patients with SA-AKI, a low ratio remained associated with lower 3-month renal recovery, longer ICU and hospital stays, higher in-hospital mortality, and greater 3-month chronic kidney disease progression after adjustment. CONCLUSION: The admission Klotho/FGF23 ratio was associated with SA-AKI, higher KDIGO stage, and short-term outcomes and showed the highest observed discrimination among the three biomarkers.

Source: Medical Principles and Practice

DOI: 10.1159/mpp/adpag028