Evaluation of the events involved in the renal changes associated with experimental models of ischemic acute kidney injury, 5/6 nephrectomy and nephrotoxicity by Amphotericin B: influence of vitamin D deficiency

• Grant number: 15/05513-1
• Support Opportunities: Regular Research Grants
• Duration: October 01, 2015 - December 31, 2017
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Rildo Aparecido Volpini
• Grantee: Rildo Aparecido Volpini
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Ana Carolina de Bragança Viciana ; Antonio Carlos Seguro ; Daniele Canale Cavicchioli ; Lucia da Conceição Andrade ; Maria Heloisa Massola Shimizu

Abstract

Ischemia/reperfusion (I/R) is the main cause of acute kidney injury (AKI). The pathophysiology of injury from I/R involves a complex exchange among renal hemodynamics, tubular injury and inflammation, as well as active process of proliferation and cell death. This complex interaction among vascular factors, tubular and inflammatory are usually followed by a repair process that can restore function and epithelial differentiation or result in chronic kidney disease (CKD) with gradual onset of fibrosis and subsequent progression to end-stage kidney disease. It has been demonstrated that the mortality of patients with CKD, besides being related to renal function, is also due to cardiovascular diseases and infections. Among the many kinds of infections, invasive fungal infections (IFI) are a major cause of morbidity and mortality in those immunocompromised or hospitalized patients with serious diseases. However, traditional hazards such as cardiovascular diseases and infections account for only half of the causes of mortality of patients with renal disease. Currently, several studies are being directed to non-traditional risk factors, such as vitamin D deficiency. The aim of this work is to evaluate the events involved in the renal changes associated with experimental models of ischemic AKI, 5/6 nephrectomy and nephrotoxicity by Amphotericin B in influence of vitamin D. Wistar rats will be subjected to surgical induction of I/R to obtain the AKI model (protocol 1), and to 5/6 nephrectomy model of CKD ( Protocol 2). The third protocol involves the use of nephrotoxicity model by amphotericin B. All animal protocols involve control and vitamin D deficient animals. We will evaluate kidney function, biochemical parameters (electrolytes, proteinuria, hormones), and hemodynamics (renal blood flow and blood pressure). Furthermore, experiments will be conducted to study the renal microvasculature, immunohistochemical studies (inflammation pathways phenotypic change, conveyors) and histomorphometry (renal injury, interstitial area and on glomerular area), protein analysis (carriers, and vascular factors growth, receivers) and evaluation of gene expression (analysis of the renin-angiotensin-system, vitamin D receptor and Klotho). (AU)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DE BRAGANCA, ANA CAROLINA; CANALE, DANIELE; GONCALVES, JANAINA GARCIA; MASSOLA SHIMIZU, MARIA HELOISA; SEGURO, ANTONIO CARLOS; VOLPINI, RILDO APARECIDO. Vitamin D Deficiency Aggravates the Renal Features of Moderate Chronic Kidney Disease in 5/6 Nephrectomized Rats. FRONTIERS IN MEDICINE, v. 5, OCT 10 2018. (10/52294-0, 15/05513-1)

GONCALVES, JANAINA GARCIA; CANALE, DANIELE; DE BRAGANCA, ANA CAROLINA; SEGURO, ANTONIO CARLOS; SHIMIZU, MARIA HELOISA MASSOLA; VOLPINI, RILDO APARECIDO. The Blockade of TACE-Dependent EGF Receptor Activation by Losartan-Erlotinib Combination Attenuates Renal Fibrosis Formation in 5/6-Nephrectomized Rats Under Vitamin D Deficiency. FRONTIERS IN MEDICINE, v. 7, JAN 5 2021. (15/05513-1, 18/12297-1, 18/04930-6)

DOS SANTOS, MICHELE SANTIAGO; CANALE, DANIELE; BERNARDO, DESIREE RITA DENELLE; SHIMIZU, MARIA HELOISA MASSOLA; SEGURO, ANTONIO CARLOS; VOLPINI, RILDO APARECIDO; DE BRAGANCA, ANA CAROLINA. The Restoration of Vitamin D Levels Slows the Progression of Renal Ischemic Injury in Rats Previously Deficient in Vitamin D. FRONTIERS IN MEDICINE, v. 8, APR 1 2021. (18/04930-6, 15/05513-1, 18/12297-1)

FERREIRA, DANIELA; DE BRAGANCA, ANA CAROLINA; VOLPINI, RILDO APARECIDO; MASSOLA SHIMIZU, MARIA HELOISA; FRANCA GOIS, PEDRO HENRIQUE; COSTA GIRARDI, ADRIANA CASTELLO; SEGURO, ANTONIO CARLOS; CANALE, DANIELE. Vitamin D deficiency is a potential risk factor for lipid Amphotericin B nephrotoxicity. PLoS Neglected Tropical Diseases, v. 13, n. 7, JUL 2019. (15/11933-3, 15/05513-1)

DE SOUZA, SAMIRA ITANA; ROCHA, EDILENE CANDIDO; FERRAZ, HALANNA ROCHA; DIAS, JESSICA AFONSO; SEGURO, ANTONIO CARLOS; VOLPINI, RILDO APARECIDO; CANALE, DANIELE; DE BRAGANCA, ANA CAROLINA; MASSOLA SHIMIZU, MARIA HELOISA; MARQUES, LUCAS MIRANDA; et al. Acute kidney injury induced by glycerol is worsened by orchiectomy and attenuated by testosterone replacement. Steroids, v. 165, JAN 2021. (15/05513-1)