Silva, AnaMendes, FilipaCarias, EduardaGonçalves, RuiFragoso, AndréDias, CarolinaTavares, NelsonCafé, HugoSantos, NélioRato, FátimaLeão Neves, PedroAlmeida, Edgar2022-09-052022-09-052019Int J Mol Sci. 2019 Mar 27;20(7):15361661-6596http://hdl.handle.net/10451/54303© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).Background: Research over the past decade has focused on the role of Klotho as a cardio protective agent that prevents the effects of aging on the heart and reduces the burden of cardiovascular disease CVD. The role of the interaction between fibroblast growth factor 23-(FGF-23)/Klotho in Klotho-mediated actions is still under debate. The main objective was to ascertain the potential use of plasmatic Klotho and FGF23 as markers for CKD-associated cardiac disease and mortality. Methods: This was a prospective analysis conducted in an outpatient diabetic nephropathy clinic, enrolling 107 diabetic patients with stage 2⁻3 CKD. Patients were divided into three groups according to their left ventricular mass index and relative wall thickness. Results: Multinomial regression analysis demonstrated that low Klotho and higher FGF-23 levels were linked to a greater risk of concentric hypertrophy. In the generalized linear model (GLM), Klotho, FGF-23 and cardiac geometry groups were statistically significant as independent variables of cardiovascular hospitalization (p = 0.007). According to the Cox regression model, fatal cardiovascular events were associated with the following cardiac geometric classifications; eccentric hypertrophy (p = 0.050); concentric hypertrophy (p = 0.041), and serum phosphate ≥ 3.6 mg/dL (p = 0.025), FGF-23 ≥ 168 (p = 0.0149), α-klotho < 313 (p = 0.044). Conclusions: In our population, Klotho and FGF23 are associated with cardiovascular risk in the early stages of CKD.engCKDCVDFGF-23LVMIklothojournal article10.3390/ijms200715361422-0067