Martins, Ana RitaAzeredo-Lopes, SofiaPereira, Sofia AzeredoSA, PereiraMoreira, InêsWeigert, André Luíz2023-12-122023-12-122023-122048-8505PURE: 77751111PURE UUID: 0160e002-cd6a-4c15-97d9-2ac76ce97caaPubMed: 38046042PubMedCentral: PMC10689163ORCID: /0000-0002-8456-9995/work/151411445Scopus: 85184770526http://hdl.handle.net/10362/161161BACKGROUND: Patients with chronic kidney disease (CKD) present a higher risk of cardiovascular (CV) morbidity and mortality compared with the general population. While there are several well-established traditional CV risk factors, few studies have addressed novel potential risk factors such as α-Klotho, asymmetric dimethylarginine (ADMA) and lean mass. METHODS: This was an observational, prospective, single-center, cohort study that included prevalent hemodialysis (online hemodiafiltration) adult patients. By univariate logistic regression models, univariate and multivariate Cox proportional hazards models, and Kaplan-Meier analysis, we evaluated the association between the levels of α-Klotho, ADMA and lean mass, with the risk of peripheral vascular disease (PVD), CV events and all-cause mortality in these patients. RESULTS: A total of 200 HD patients was included. We found that increased levels of log-α-Klotho were significantly associated with decreased odds of both PVD [odds ratio (OR) 0.521, 95% confidence interval (CI) 0.270-0.954, P = .034] and CV events (OR 0.415, 95% CI 0.203-0.790, P = .01), whereas increased levels of log-ADMA were only significantly associated with increased odds of PVD (OR 13.482, 95% CI 5.055-41.606, P < .001). We also found that the levels of log-α-Klotho (HR 0.357, 95% CI 0.140-0.906, P < .05) and lean mass (HR 0.187, 95% CI 0.042-0.829, P < .05), but not log-ADMA, were significantly associated with the risk of all-cause mortality, even after adjusting for possible confounding variables. CONCLUSIONS: Novel long-term clinical associations were generated that support α-Klotho and lean mass as novel CV risk factors in hemodialysis patients.10961758engADMAbioimpedancebiomarkersmortalityperipheral vascular diseasejournal article10.1093/ckj/sfad166