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Evaluation of the protective effect of pre-and post-conditioning in transient renal ischemia model: an experimental study in rats with balanced general anesthesia

Grant number: 13/09874-3
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): July 01, 2013
Effective date (End): December 31, 2015
Field of knowledge:Health Sciences - Medicine - Surgery
Principal Investigator:Norma Sueli Pinheiro Módolo
Grantee:Renata Torres Bueno
Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil


The preconditioning is described as a protective mechanism, initially applied to study the damage prevention of myocardial ischemia after minor episodes of coronary occlusion (ischemic preconditioning) or the administration of certain drugs (pharmacological preconditioning). Method is considered to adapt the tissue ischemic episode, prior to a longer lasting stimulus, in order to reduce the extent of injury. The tolerance to ischemia is induced regulation of endothelial function, blood flow and decreased activity of macrophages and neutrophils. Acute kidney injury (AKI) is characterized by rapid decline in kidney function that can potentially be reversible, has variable incidence depending on the criteria used for its definition. Clinical evidence has shown that even small increases in serum creatinine levels above the normal range are associated with increased morbidity and mortality, as well as interfere with progression to chronic kidney disease. In consensus published by Bellomo et al., 2004 was created the RIFLE criteria, which defined the LRA based on plasma creatinine and urinary output. This consensus classified the LRA in 3 categories of severity (risk, injury and failure) and 2 clinical categories (loss and end-stage renal failure). In 2007, the RIFLE criteria was modified by a new panel a bit more elaborate and applying simpler: the criteria of AKIN (Acute Kidney Injury Network). This defines AKI as an abrupt reduction in renal function with an absolute increase of 0.3 mg \ dL or 50% increase in the baseline creatinine, or oliguria. Both AKIN criterion as the criterion RIFLE based on creatinine as a biomarker of renal function. However, the change in serum creatinine can not differentiate the causes of AKI as hypovolemia, changes in renal perfusion, urinary tract obstruction or parenchymal injury. There is also strong evidence that the change in serum creatinine levels may not occur until hours or days after the onset of renal injury, and is a very specific marker since it suffers great influences of changes in muscle mass and tubular secretion factors and non-renal as weight, race, sex, and drugs used protein intake. The research aims at evaluating the protective effect of pre-and post-ischemic, alone or together after acute kidney injury in rats subjected to renal ischemia under general balanced anesthesia; side: correlating early renal markers such as NGAL, KIM-1 and IL-18 with the AKIN criteria, histological kidney injury relate to the dosage of biomarkers and the criterion of AKIN. Will be included in the study 40 Winstar rats, males with equivalent weights, provided by the Central Animal Facility of the Campus of Botucatu, randomly divided into 5 groups of 8 animals: G0, G1, G2, G3 and G4. All will be induced with inhalational isoflurane in inspired concentration 3-4% and a rate of 4 liters per minute for 5 min and kept under balanced general anesthesia. Be hydrated with Ringer lactate infusion pump after each blood sampling 1.5 mL will be held reset with 3 mL of Ringer lactate. In all groups will be performed laparotomy and right nephrectomy, 30 minutes after the last release clamping drugs will be suspended 12 hours after reopening of laparotomy and left nephrectomy. The data will be evaluated in four moments: M0, vital signs, the M1, vital signs, serum creatinine and serum NGAL, in M2, will be further evaluated vital signs and serum NGAL and M3 creatinine and serum NGAL , urinary NGAL, KIM-1 to the IL18 and histological analysis.Keywords: Preconditioning - Postconditioning - Renal Ischemia - Mice (AU)

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