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Role of innate immunity in the progressive nephropathy that follows brief nitric oxide inhibition and salt overload

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Author(s):
Karin Carneiro de Oliveira
Total Authors: 1
Document type: Doctoral Thesis
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD)
Defense date:
Examining board members:
Roberto Zatz; Mirian Aparecida Boim; Luiz Fernando Onuchic; Maria Oliveira de Souza
Advisor: Roberto Zatz
Abstract

NO synthase inhibition by L-NAME plus high-salt diet (HS) is a model of Chronic Kidney Disease characterized by marked hypertension and renal injury. With the cessation of treatment, most of these changes subside, but progressive renal injury develops, associated with persistent low-grade renal inflammation. We investigated whether innate immunity, and in particular the NF-kB system, is involved in this process. Male Munich-Wistar rats received HS and L-NAME, 32 mg/Kg/d, while control rats received HS only. Treatment was ceased after 4 weeks when 30 rats were studied. Additional rats were studied at 8 weeks (N=30) and 28 weeks (N=30). As expected, HS+L-NAME promoted severe hypertension, albuminuria, and renal injury after 4 weeks of treatment, whereas innate immunity activation was evident. After discontinuation of treatments, partial regression of renal injury and inflammation occurred, along with persistence of innate immunity activation. At 28 weeks, glomerular injury worsened, while renal inflammation persisted and renal innate immunity remained activated. Administration of the NF-kB inhibitor pyrrolidine dithiocarbamate (PDTC) in concomitancy with the four-week HS+L-NAME treatment prevented the development of renal injury and inflammation, an effect that lasted throughout the 28-week period of observation. Early activation of innate immunity may be crucial to the initiation of renal injury in the HS+LNAME model, and to the autonomous progression of chronic nephropathy even after cessation of the original insult (AU)

FAPESP's process: 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
Grantee:Karin Carneiro de Oliveira
Support type: Scholarships in Brazil - Doctorate (Direct)