Advanced glycation end products (ages): associations with mineral and bone disorders and cardiovascular disease in chronic kidney disease

• Grant number: 15/16544-5
• Support Opportunities: Research Grants - Young Investigators Grants
• Duration: December 01, 2016 - May 31, 2021
• 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

Chronic kidney disease (CKD) is associated with mineral and bone disorders (MBD) and cardiovascular disease (CVD), common complications of CKD. Advanced glycosylation end-products (AGEs) are involved with CVD and CKD-MBD, however, pathophysiology still poorly understood. AGEs have potential to be used as a marker of tissue damage or therapeutic target. A non-invasive instrument (AGE-Reader) was developed to quantify the tissue deposition of AGEs using skin auto-fluorescence reading (sAF), method validated in CKD, however, it is not known if he is able to reflect the concentration of AGEs in bone tissue or if it could be a useful marker. This study aims to investigate the relationships between AGEs, MBD and CVD parameters in patients at different stages of CKD, through evaluation of clinical-demographic and general biochemistry data, AGEs on skin (AGE-Reader) and bone tissue (immunohistochemistry for AGEs), by sAF and serum levels (carboxymethyllisine and pentosidine), sclerostin, deoxypyridinoline, collagen type-I C-telopeptide, bone histomorphometric analysis, bone densitometry, vascular calcification by radiographs (pelvis and hands), echocardiogram data, and classical markers of CVD. Gene expression of Wnt pathway regulators in bone tissue and its relations with AGEs will be assessed by PCRrt, as well the expression of protein lysil oxidase, which regulates collagen degradation. Will be included CKD patients at stages 3-4 (N=30), under peritoneal dialysis (N=30) and hemodialysis (N=30). A control group of 50 healthy adult subjects will be assessed for comparison matched for age and sex. The originality of this study lies on the simultaneous study of the relationships among AGEs, by a new method, MBD and CVD parameters in Brazilian patients with different stages of CKD. This proposal was approved by FCM-UNCAMP Ethics Committee (CAAE: 38108314.6.0000.5404, 45777015.5.0000.5404 e 45943115.9.0000.5404). (AU)