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Doctoral Thesis
DOI
https://doi.org/10.11606/T.5.2018.tde-14082018-123532
Document
Author
Full name
Carolina Martinez Romão
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2018
Supervisor
Committee
Furukawa, Luzia Naoko Shinohara (President)
Peres, Maria Angelica
Reis, Luciene Machado dos
Romão Junior, João Egidio
Title in Portuguese
Evolução da injúria renal aguda causada pela sobrecarga de sódio na dieta: tratamento com N-acetilcisteína e os efeitos no metabolismo ósseo
Keywords in Portuguese
Acetilcisteína
Distúrbio mineral e ósseo na doença renal crônica
Isquemia
Lesão renal aguda
Reperfusão
Abstract in Portuguese
Estudos tem demonstrado que a injúria renal aguda (IRA) pode evoluir para doença renal aguda ou crônica, principalmente quando associada à comorbidades como a hipertensão sal-dependente. Além disso, o desenvolvimento da perda de função renal é comumente associado a distúrbios mineral e ósseo. O uso de antioxidantes como a N-acetilcisteína (NAC) tem sido utilizado para prevenir a lesão da IRA, no entanto pouco se sabe sobre o uso deste medicamente em um período prolongado e os seus efeitos no metabolismo mineral e ósseo. Sendo assim os objetivos do presente estudo foram avaliar a repercussão da sobrecarga de sódio na dieta em modelo de IRA com ou sem tratamento com NAC, e observar a influência da IRA, dieta hipersódica e tratamento no metabolismo mineral e ósseo após 10 semanas de protocolo. Para isto foram utilizados ratos machos Wistar alimentados com dieta normossódica (0,5% Na - NS) ou hipersódica (3,2% Na - HS), tratados com ou sem NAC (IR NAC) (600mg/L) e submetidos à cirurgia de isquemia (45 minutos) e reperfusão renal bilateral (IR) ou Sham. Os animais foram acompanhados por 10 semanas após a cirurgia. Foram avaliadas pressão arterial caudal, função renal, metabolismo mineral e histomorfometria óssea. Os animais que sofreram IR e foram alimentados com dieta HS apresentaram maior excreção de sódio, cálcio e fósforo e albuminúria. A albuminúria correlacionou-se com o aumento do PTH induzindo a um maior tecido osteoide e superfície de osteoblastos nestes animais. A NAC diminuiu excreção de sódio, cálcio, fósforo, albuminúria e PTH, mas causou a diminuição do volume ósseo e aumento da separação trabecular. A ingestão do sódio influenciou nos níveis séricos altos de 1-25(OH)2D e baixos de FGF-23. Estes resultados sugerem que a sobrecarga de sal na dieta causou evolução da IRA após 10 semanas. Essa perda de função renal aumentou o PTH, volume osteoide e osteoblastos. Em contrapartida, o tratamento com a NAC preveniu a progressão da disfunção renal, mas levou à perda de massa óssea
Title in English
Acute kidney injury induced by diet sodium overload: N-acetylcysteine treatment and its effects on bone metabolism
Keywords in English
Acetylcysteine
Acute kidney injury
Chronic kidney disease-mineral and bone disorder
Ischemia
Reperfusion
Abstract in English
Studies have shown that acute kidney injury (AKI) can progress to acute or chronic kidney disease especially when associated with co-morbidities such as salt-dependent hypertension. In addition to impairment of renal function there is association with mineral and bone disorders. The antioxidants such as N-acetylcysteine (NAC) has been used to prevent the AKI; however; the prolonged use and its effects in mineral and bone metabolism is not well studied. The aim of the study was to evaluate dietary sodium overload repercussion on the AKI associated to NAC treatment and to observe its effects on bone metabolism after 10 weeks. Were used Wistar rats were fed with normal sodium (0.5% NaCl - NS) or high sodium (3.2% NaCl - HS) diet and treated or not with NAC (600 mg/L) and submitted to renal ischemia (45 minutes) and reperfusion (IR) or Sham surgery. The animals were followed up for 10 weeks after surgery. We evaluated caudal blood pressure, renal function, mineral metabolism and bone histomorphometry. In our results urinary sodium, calcium, phosphorus excretion and albuminuria were higher in HS IR animals. There was a positive correlation between albuminuria and PTH leading to osteoid tissue and surface of osteoblasts augmentation in these animals. In other hand, NAC decreased sodium, calcium, phosphorus excretion, albuminuria and PTH; however, it was observed lower bone volume and higher trabecular separation. Sodium intake had an isolated effect on 1-25(OH)2D and FGF-23. These results suggest that overload salt diet caused AKI development. Loss of renal function increased PTH, osteoid volume and osteoblasts Treatment with NAC prevented renal function impairment, however it induced to bone mass loss
 
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Publishing Date
2018-08-14
 
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