Study of the vulnerability of the remaining kidney as a result of unilateral nephrectomy, when subjected to crystalline nephropathy

• Grant number: 22/10627-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: October 01, 2023
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Maria Oliveira de Souza
• Grantee: Neydiana Belize de Pina Lopes
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The incidence of progressive kidney disease is a serious public health problem. For terminally ill patients, the best therapeutic measure is kidney transplantation and studies have shown a better prognosis when this kidney comes from a living donor. However, in the donor, unilateral nephrectomy (NU) can result in overload of the remaining kidney, which may become a relevant factor in the development of acute kidney injury (AKI) and the development of a possible vulnerability of this kidney. In addition, living donors are mostly young and, in the future, due to age and/or genetic predisposition, they may develop crystalline nephropathy and other comorbidities that potentiate the development of kidney diseases. Thus, the present study aims to investigate the function of the remaining kidney after a unilateral nephrectomy as well as its response to crystalline nephropathy and the possible factors and negotiation involved in the vulnerability of this kidney. For this purpose, 8-week-old mice of the C57BL/6J strain will be used, classified into control groups (Sham), treated with sodium oxalate (9 mg/100g, single intraperitoneal injection to induce crystalline nephropathy, 24hrs before euthanasia, NaOx), unilateral nephrectomy (NU) surgery, unilateral nephrectomy and treated with sodium oxalate (NU/NaOx). After the surgical procedures, the animals will be monitored for 7 or 42 days to evaluate metabolic parameters and renal function. At the end of each period, each animal will be submitted to isoflurane anesthesia, blood and urine collection, removal of the contralateral kidney and euthanasia by exsanguination according to the protocol approved by the ethics committee (CEUA-ICB/USP, number 4550140422). Metabolic, renal and plasma parameters will be evaluated using specific kits by color method. Renal morphology will be evaluated by color techniques, including Hematoxylin & Eosin (HE), Masson's trichrome and Periodic Acid Schiff (PAS). The expression of mRNA and proteins will be evaluated by quantitative PCR and western blotting, respectively. Tissue localization of proteins will be monitored by immunofluorescence or immunohistochemistry. Statistical analysis of the data will be performed by ANOVA, two-way, completely randomized, followed by the Bonferroni post test, performed using the GraphPad Prism software. Values of p<0.05 will be statistically considered. Results will be presented as a mean value ± standard deviation. (AU)