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Pathogenesis and treatment of chronic kidney disease: role of innate immunity in glomerular, tubular and interstitial injury

Grant number: 12/10926-5
Support type:Research Projects - Thematic Grants
Duration: December 01, 2012 - November 30, 2018
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Roberto Zatz
Grantee:Roberto Zatz
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Co-Principal Investigators:Clarice Kazue Fujihara
Assoc. researchers:Andrea Cecilia Dorión Rodas ; Antonio Carlos Seguro ; Camilla Fanelli ; Denise Maria Avancini Costa Malheiros ; Flavia Gomes Machado ; José Eduardo Krieger ; Mariane Tami Amano ; Niels Olsen Saraiva Câmara ; Patricia Semedo Kuriki ; Simone da Costa Alarcon Arias
Associated grant(s):14/16882-5 - Kidney Week 2014, AR.EXT
Associated scholarship(s):18/03610-8 - Role of the TLR4/NFkB system and the NLRP3 inflammatory pathways in prolonged exposure of tubular cells to elevated albumin concentrations, BP.TT
17/10329-0 - A treatment using a component of innate immunity inhibitor on adriamycin nephropathy, BP.IC
16/08622-9 - Innate immunity components analysis in renal tissues of rats with glomerular hypertension, BP.IC
+ associated scholarships 16/08525-3 - Effect of treatment with an innate immunity component inhibitor in adriamycin nephropathy, BP.IC
15/25368-6 - Role of NFkB system and NLRP3 inflammasome in the chronic inhibition of nitric oxide model, BP.MS
15/08253-0 - The role of innate immunity in chronic kidney disease stablished after recovery nephropathy induced by temporary inhibition of nitric oxide associated with a saline overload, BP.DD
13/26726-8 - Role of hypoxia in the activation of innate immunity in the progression of chronic kidney disease associated with ablation 5/6 renal model, BP.DR
14/17031-9 - The role of NF-kB system in the progression of renal disease associated with transient administration of L-NAME, BP.IC
13/26947-4 - The role of innate immunity in CKD following treatment with a temporary overload of the adenine diet, BP.MS
13/11929-0 - Effect of glomerular barrier dysfunction on proximal tubular cell innate immunity, BP.DR
13/12256-0 - The role of innate immunity in pathogenesis of diabetic nephropathy, BP.DD
13/00721-0 - Effect on innate immunity of glomerular and tubular cells prolonged exposure to mechanical stretching, BP.PD - associated scholarships

Abstract

Chronic Kidney Disease (CKD) involves the participation of a series of inflammatory events that culminate in fibrosis of the renal parenchyma. The reasons why these processes, which involve the activation of phenomena related to adaptive immunity, are triggered in the absence of microbial antigens or other foreign proteins are uncertain. With the new knowledge about the innate immunity, accumulated since the discovery of toll-like receptors (TLRs) in the mid-1980s and expanded in recent years with the description of intracellular receptors and inflamasomes, and of their interaction with the NF-kB system, these questions begin to be answered. In CKD, analogously to what is believed to occur in gout and in pneumoconiosis - inflammatory responses evoked by foreign bodies - it is possible that activation of innate immunity represents the link between nonspecific events, such as stretching of the glomerular wall, and inflammatory processes leading to renal fibrosis and glomerulosclerosis. The hypothesis on which the present research projects are centered is that at least some forms of CKD result of, and/or are perpetuated by, the activation of innate immunity by factors such as mechanical injury to the glomeruli or the exposure of cells to chemical aggression such as high levels of glucose or proteins. These projects will also clarify previous observations from our laboratories and will afford the opportunity to investigate new therapies designed to contain the inflammatory events that conduce to CKD and its progression. (AU)

Scientific publications (8)
(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)
TONO REMPEL, LISIENNY CAMPOLI; FAUSTINO, VIVIANE DIAS; FORESTO-NETO, ORESTES; FANELLI, CAMILLA; ALARCON ARIAS, SIMONE COSTA; DA SILVA MOREIRA, GIZELY CRISTINA; NASCIMENTO, THALITA FABIANA; AVILA, VICTOR FERREIRA; COSTA MALHEIROS, DENISE MARIA AVANCINI; SARAIVA CAMARA, NIELS OLSEN; FUJIHARA, CLARICE KAZUE; ZATZ, ROBERTO. Chronic exposure to hypoxia attenuates renal injury and innate immunity activation in the remnant kidney model. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, v. 317, n. 5, p. F1285-F1292, NOV 2019. Web of Science Citations: 0.
ANDRADE-OLIVEIRA, VINICIUS; FORESTO-NETO, ORESTES; MIZUNO WATANABE, INGRID KAZUE; ZATZ, ROBERTO; SARAIVA CAMARA, NIELS OLSEN. Inflammation in Renal Diseases: New and Old Players. FRONTIERS IN PHARMACOLOGY, v. 10, OCT 8 2019. Web of Science Citations: 0.
FREGNAN ZAMBOM, FERNANDA FLORENCIA; OLIVEIRA, KARIN CARNEIRO; FORESTO-NETO, ORESTES; FAUSTINO, VIVIANE DIAS; AVILA, VICTOR FERREIRA; ALBINO, AMANDA HELEN; ALARCON ARIAS, SIMONE COSTA; VOLPINI, RILDO APARECIDO; AVANCINI COSTA MALHEIROS, DENISE MARIA; SARAIVA CAMARA, NIELS OLSEN; ZATZ, ROBERTO; FUJIHARA, CLARKE KAZUE. Pathogenic role of innate immunity in a model of chronic NO inhibition associated with salt overload. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, v. 317, n. 4, p. F1058-F1067, OCT 2019. Web of Science Citations: 0.
AVILA, VICTOR F.; FORESTO-NETO, ORESTES; ARIAS, SIMONE C. A.; FAUSTINO, VIVIANE D.; MALHEIROS, DENISE M. A. C.; CAMARA, NIELS O. S.; ZATZ, ROBERTO; FUJIHARA, CLARICE K. Pathogenic role of angiotensin II and the NF-kappa B system in a model of malignant hypertensive nephrosclerosis. HYPERTENSION RESEARCH, v. 42, n. 6, p. 779-789, JUN 2019. Web of Science Citations: 1.
FAUSTINO, VIVIANE DIAS; ALARCON ARIAS, SIMONE COSTA; AVILA, VICTOR FERREIRA; FORESTO-NETO, ORESTES; FREGNAN ZAMBOM, FERNANDA FLORENCIA; MACHADO, FLAVIA GOMES; DOS REIS, LUCIENE MACHADO; MARIA, DENISE; MALHEIROS, AVANCINI COSTA; VOLPINI, RILDO APARECIDO; SARAIVA CAMARA, NIELS OLSEN; ZATZ, ROBERTO; FUJIHARA, CLARICE KAZUE. Simultaneous activation of innate and adaptive immunity participates in the development of renal injury in a model of heavy proteinuria. BIOSCIENCE REPORTS, v. 38, n. 4 AUG 31 2018. Web of Science Citations: 3.
FORESTO-NETO, ORESTES; AVILA, VICTOR FERREIRA; ALARCON ARIAS, SIMONE COSTA; FREGNAN ZAMBOM, FERNANDA FLORENCIA; TONO REMPEL, LISIENNY CAMPOLI; FAUSTINO, VIVIANE DIAS; MACHADO, FLAVIA GOMES; AVANCINI COSTA MALHEIROS, DENISE MARIA; ABENSUR, HUGO; SARAIVA CAMARA, NIELS OLSEN; ZATZ, ROBERTO; FUJIHARA, CLARICE KAZUE. NLRP3 inflammasome inhibition ameliorates tubulointerstitial injury in the remnant kidney model. LABORATORY INVESTIGATION, v. 98, n. 6, p. 773-782, JUN 2018. Web of Science Citations: 6.
FUJIHARA, CLARICE K.; KOWALA, M. C.; BREYER, M. D.; SENA, CLAUDIA R.; RODRIGUES, MARILIZA V.; ARIAS, SIMONE C. A.; FANELLI, CAMILLA; MALHEIROS, DENISE M.; JADHAV, P. K.; MONTROSE-RAFIZADEH, CHAHRZAD; KRIEGER, JOSE E.; ZATZ, ROBERTO. A Novel Aldosterone Antagonist Limits Renal Injury in 5/6 Nephrectomy. SCIENTIFIC REPORTS, v. 7, AUG 11 2017. Web of Science Citations: 3.
FANELLI, CAMILLA; ARIAS, SIMONE C. A.; MACHADO, FLAVIA G.; OKUMA, JESSICA K.; MALHEIROS, DENISE M. A. C.; AZEVEDO, HATYLAS; MOREIRA-FILHO, CARLOS A.; CAMARA, NIELS O. S.; FUJIHARA, CLARICE K.; ZATZ, ROBERTO. Innate And Adaptive Immunity are Progressively Activated in Parallel with Renal Injury in the 5/6 Renal Ablation Model. SCIENTIFIC REPORTS, v. 7, JUN 9 2017. Web of Science Citations: 7.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.