title: Precocious obesity predisposes the development of more severe cisplatin-induced acute kidney injury in young adult mice.
abstract: Obesity and its consequences can damage the kidney over time. However, less is known about the impact of developing overweight/obesity during childhood on the kidney in adulthood and the renal impact of a superimposed acute kidney injury (AKI). This study evaluated the effect of obesity induced by a high-fat diet initiated soon after weaning on the adult life of mice and their response to superimposed nephrotoxic effects of cisplatin. C57BL/6 post-weaning mice (3 weeks old) were divided into a control group (CT, n = 12) and a high-fat diet group (HF, n = 12). After 9 weeks, animals were further divided into the following groups: CT, CT treated with a single dose of cisplatin (CTCis, 20 mg/kg, i.p.), HF and HF treated with cisplatin (HFCis). The HF group exhibited higher body weight gain compatible with a moderate obesity. Obese mice presented increased visceral adiposity, hyperkalemia, sodium retention, glomerular hyperfiltration and proteinuria, without any significant changes in blood pressure and glycemia. AKI induced by cisplatin was exacerbated in obese animals with a 92% reduction in the GFR versus a 31% decrease in the CTCis group; this sharp decline resulted in severely elevated serum creatinine and urea levels. Acute tubular necrosis induced by cisplatin was worsened in obese mice. The HFCis group exhibited robust systemic and intrarenal inflammation that was significantly higher than that in the CTCis group; the HFCis group also showed a higher degree of renal oxidative stress. In conclusion, the moderate degree of obesity induced shortly after weaning resulted in mild early renal alterations, however, obese young animals were prone to develop a much more severe AKI induced by cisplatin.
authors.affiliation: Renal Division, Department of Medicine-Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Rosemara S
authors.initials: RS
authors.lastname: Ribeiro
authors.affiliation: Renal Division, Department of Medicine-Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Clevia S
authors.initials: CS
authors.lastname: Passos
authors.affiliation: Renal Division, Department of Medicine-Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Antônio S
authors.initials: AS
authors.lastname: Novaes
authors.affiliation: Renal Division, Department of Medicine-Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Edgar
authors.initials: E
authors.lastname: Maquigussa
authors.affiliation: Renal Division, Department of Medicine-Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Glória
authors.affiliation: Pathology Department-Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Iria
authors.initials: I
authors.lastname: Visoná
authors.affiliation: Renal Division, Department of Medicine-Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Olinda
authors.initials: O
authors.lastname: Ykuta
authors.affiliation: Nutrition Physiology-Department of Physiology-Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Lila M
authors.initials: LM
authors.lastname: Oyama
authors.affiliation: Renal Division, Department of Medicine-Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Mirian A
authors.identifier: http://orcid.org/0000-0001-7500-8371
authors.initials: MA
authors.lastname: Boim
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D000818:Animals; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects*; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000150:complications / Q000503:physiopathology*; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000293:injuries / Q000503:physiopathology; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000150:complications / Q000503:physiopathology*; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D002945:Cisplatin