Plasmatic Klotho and FGF23 Levels as Biomarkers of CKD-Associated Cardiac Disease in Type 2 Diabetic Patients

• Main Authors: Ana Paula Silva, Filipa Mendes, Eduarda Carias, Rui Baptista Gonçalves, André Fragoso, Carolina Dias, Nelson Tavares, Hugo Mendonça Café, Nélio Santos, Fátima Rato, Pedro Leão Neves, Edgar Almeida
• Format: Article
• Language: English
• Published: MDPI AG 2019-03-01
• Series: International Journal of Molecular Sciences
• Subjects: klotho; FGF-23; CKD; CVD; LVMI
• Online Access: https://www.mdpi.com/1422-0067/20/7/1536

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&#8211;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 (<i>p</i> = 0.007). According to the Cox regression model, fatal cardiovascular events were associated with the following cardiac geometric classifications; eccentric hypertrophy (<i>p</i> = 0.050); concentric hypertrophy (<i>p</i> = 0.041), and serum phosphate &#8805; 3.6 mg/dL (<i>p</i> = 0.025), FGF-23 &#8805; 168 (<i>p</i> = 0.0149), &#945;-klotho &lt; 313 (<i>p</i> = 0.044). Conclusions: In our population, Klotho and FGF23 are associated with cardiovascular risk in the early stages of CKD.