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Analysis of the transition from acute ischemic renal injury to chronic kidney disease and the contribution of diabetes mellitus in this process

Grant number: 16/12354-0
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): September 01, 2018
Effective date (End): March 31, 2021
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal researcher:Maria Oliveira de Souza
Grantee:Mariana Charleaux de Ponte
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Acute kidney injury (AKI) secondary to the ischemia and reperfusion process is one of the most common causes for the progression of chronic kidney disease (CKD) and, consequently, loss of renal function. Diabetes mellitus, or type I diabetes, is a metabolic condition associated with hyperglycemia and diabetic kidney disease with loss of renal function. However, the pathophysiological mechanisms associated with the transition from AKI to CKD and the contribution of diabetes mellitus in this process are poorly understood. Thus, the general objective of the current proposal is to identify the mechanisms responsible for the transition from acute renal injury to chronic renal disease in experimental models of renal ischemia and reperfusion and / or streptozotocin-induced diabetes. The methods that will be used in the current proposal include: ischemia (30 minutes) and renal reperfusion (2 and 28 days); analysis of physiological and metabolic parameters; assessment of plasma creatinine and urea concentration; analysis of the ratio of kidney weight under body weight; Western blotting and RT-PCR to evaluate protein and mRNA expression for factors associated with endoplasmic reticulum, apoptosis and fibrosis stress, as well as factors associated with tissue repair. The challenges of the current proposal will be to point out the factors and mechanisms associated with the transition from post-ischemic AKI to CKD and the contribution of diabetes mellitus in this process. Statistical analysis of the data will be performed by one-way ANOVA, completely randomized, followed by the post-hoc Bonferroni test. Values of p <0.05 will be considered statistically significant and the results will be presented as an average value ± standard error.