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Contribution of urinary stones in the progression of renal injury in rats

Grant number: 19/06358-0
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): August 01, 2019
Effective date (End): December 31, 2020
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Maria Oliveira de Souza
Grantee:Larissa de Araújo
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The renal lithiasis or urinary stones is a frequent pathology in clinical practice with serious consequences depending on the duration and the frequency of recurrence of the insult. Although your clinical importance, little is known about the cellular mechanisms associated with acute kidney injury (AKI) due to the presence of kidney stones; the progression from the acute stage to chronic kidney disease (CKD) or the recurrence of stones in anticipation of the progression of the AKI to CKD. Our hypothesis is that in the acute phase of renal lithiasis, the endoplasmic reticulum stress, as well as inflammation, are partly responsible for the injury. In the later period, there may be tissue repair or progression of chronic kidney disease with or without recurrence of stones. At this stage of the disease, should prevail the endoplasmic reticulum stress, inflammation and fibrosis. The aim of this study is to point the main cellular mechanisms involved in the AKI and progression to the CKD with or without the recurrence of stones. To this, Wistar rats to be used with 60 days of age randomly divided into 2 groups (control and treated, n = 10 per group) for each step of treatment. The animals shall be subject to an intraperitoneal injection of sodium oxalate (7mg/100 g/day) dissolved in saline (0.9%) for three consecutive days. After 24 hours of the last injection, a group of animals will be subjected to euthanasia and the remaining group will be observed for 30 days. At the end of this period, a group of animals will be subjected to euthanasia and the remaining group, before euthanasia, will be resubmitted to intraperitoneal injections of sodium oxalate for three consecutive days, for observation of the recurrence of urinary stones. It should be observed that each group treated will have your control group. At the end of each treatment, under anesthesia with ketamine and xylazine (5 and 50 mg/kg, respectively) the animals will be subject to the collection of blood, urine and kidney removal. The techniques of Western blotting, immunofluorescence, and Immunohistochemistry will be used to evaluate the expression and distribution of proteins. qPCR will be used for mRNA expression evaluation. Statistical analysis will be performed by analysis of variance (ANOVA, two-way), followed by the post hoc Bonferroni test. The results are presented as mean ± standard error and p values are considered statistically significant < 0.05.