Acute kidney injury and progression of renal failure after fetal programming in the offspring of diabetic rats

BACKGROUND: Diseases of adulthood, such as diabetes and hypertension, may be related to changes during pregnancy, particularly in kidney. We hypothesized that acute kidney injury progresses more rapidly in cases of fetal programming.METHODS: Diabetic dams' offspring were divided into: CC (controls, receiving vehicle); DC (diabetics, receiving vehicle); CA (controls receiving folic Acid solution, 250 mg/kg); and DA (diabetics receiving folic acid solution). Renal function tests, morphometry, gene, and protein expression of epithelial mesenchymal transition(EMT) markers were analyzed by qPCR and immunohistochemistry, respectively.RESULTS: Creatinine, urea, Bowman's space, and EMT markers were increased in CA and DA groups. TGF-beta 3,actin,and fibronectin expression was higher in CA and DA, with significant increase in DA compared to CA 2-mo offspring. There was higher expression level ofTGF-beta 1,TGF-beta 3, fibronectin, and vimentin in the offspring of diabetic dams at 5 mo. Increases in TGF-beta 1 and TGF-beta 3 were more evident in the offspring of diabetic dams.CONCLUSION: Fetal programming promotes remarkable changes in kidney morphology, and function in offspring and renal failure progression may be faster in younger offspring of diabetic dams subjected to an additional injury.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Fundacao de Ensino e Pesquisa de Uberaba (FUNEPU, Brasil)Triangulo Mineiro Fed Univ, Biol & Nat Sci Inst, Dept Genet Ecol & Gen Pathol, Gen Pathol Discipline, Uberaba, BrazilTriangulo Mineiro Fed Univ, Biol & Nat Sci Inst, Dept Biochem Mol Biol Pharmacol Physiol & Chem, Discipline Physiol, Uberaba, BrazilFed Univ São Paulo UNIFESP, Dept Med, Div Nephrol, São Paulo, BrazilUniv São Paulo, Inst Biomed Sci, Dept Immunol, São Paulo, BrazilFed Univ São Paulo UNIFESP, Dept Med, Div Nephrol, São Paulo, BrazilWeb of Scienc