Association of Klotho protein with the risk of late complications in cancer survivors.

Abstract

e24128 Background: Chemotherapy (CT) may cause late toxicities and accelerate aging. Klotho (Kl) is a protein involved in tissue homeostasis, and its deficit has been related to early aging and comorbidities. Our objective was to explore the correlation between plasma levels of KI and the risk to develop late toxicities and comorbidities after CT. Methods: Pilot retrospective study of patients included in the CARDIOTOX registry (Eur Heart J 2020;14:1720-9) (1,324 pts). All patients had received CT for a malignant condition. Plasma levels of a-Kl were measured by ELISA and correlated with: 1) comorbidities, assessed using the Charlson Comorbidity Index (CCI) and the CIRS-G score; 2) hospitalizations (H); and 3) visits to the emergency ward (EW) (unrelated to cancer or its treatment). Results: 185 patients were included (age 57 [25-88], 90% women, 78% with breast cancer. Median follow-up was 124 months (95% IC:116-131), CCI deteriorated in 56 patients (30%) and CIRS-G in 97 (52%). Patients with Kl ≥ 580 pg/mL at baseline had a lower risk of increased comorbidities, as assessed by the CCI (HR: 0.184; 95% CI:0.10-0.33; P<0.001) or the CIRS-G score (HR:0.324; 95% IC: 0.21-0.48; P<0.001). The number of H and EW visits for non-oncologic reasons per year was 0.05 (0-0.6) and 0.22 (0-1.9), respectively. Patients with Kl ≥ 580 pg/mL at baseline had a significantly lower risk of H for non-oncologic reasons (HR:0.277; 95% IC:0.143-0,538). No relationship was detected between KL and EW visits. KI measurements obtained at 6 and 24 months after the initiation of CT did not improve the biomarker’s predictive capacity. Conclusions: This exploratory study suggests that normal Kl levels protect against the development or worsening of comorbidities and late complications in cancer survivors. These results should be validated in the entire cohort of patients included in the CARDIOTOX registry. Variables correlated with increased comorbidity (CCI) in the Cox regression analysis. Variable b SE P Exp(B) (95%IC) Klotho ≥580 -1,404 ,405 ,001 0,246 (0.111-0.543) Age ,055 ,025 ,027 1,056 (1.006-1.108) Radiotherapy 3,161 ,997 ,002 23,605 (3.354-166.590)