Effects of dapagliflozin on bone tissue of hemodialysis patients

• Grant number: 22/15002-8
• Support Opportunities: Regular Research Grants
• Duration: September 01, 2023 - August 31, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Rodrigo Bueno de Oliveira
• Grantee: Rodrigo Bueno de Oliveira
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

One of the biggest health challenges in the world is to reduce cardiovascular complications in patients with chronic kidney disease (CKD). Recent evidence has shown that gliflozins are associated with a 30% reduction in the risk of death and progression of mild/moderate CKD. Experimental data suggest that gliflozins may positively interfere with serum Klotho concentration. The potential extent of this benefit to dialysis patients is limited by the lack of pharmacokinetic and bone metabolism studies. Our group completed a pharmacokinetic study of dapagliflozin, which results revealed favorable pharmacokinetic properties and tolerability in patients under dialysis. Considering the high prevalence of bone disease in this population, a study about the influence of gliflozins on the metabolism of bone tissue in hemodialysis patients is critical. Objective: To evaluate the effects on bone metabolism of dapagliflozin in hemodialysis patients. Materials and Methods: Prospective, open, randomized clinical trial for maintenance of standard care (CONTROL group) versus maintenance of standard care + dapagliflozin 10 mg PO/day (DAPA group) for 24 weeks. The aim is to evaluate the effects of using dapagliflozin on bone tissue in hemodialysis patients. Inclusion criteria: > 18 years, > 3 months on hemodialysis and clinical stability; exclusion criteria: liver dysfunction, pregnancy or breastfeeding, use of gliflozins, AMI in the last 2 months; 80 included patients will be randomized to the CONTROL and DAPA groups. The primary outcome will be between-group comparison of the change in the following parameters (baseline versus end of study): parathormone, calcium, phosphate, alkaline phosphatase, tartrate-5b-resistant acid phosphatase, sclerostin, DKK1, osteocalcin, fibroblast growth factor-23 and Klotho. Hypothesis: the use of dapagliflozin in hemodialysis patients should increase the serum concentration of Klotho protein in hemodialysis patients. (AU)