title: Mice rescued from severe malaria are protected against renal injury during a second kidney insult.
abstract: Malaria is a worldwide disease that leads to 1 million deaths per year. Plasmodium falciparum is the species responsible for the most severe form of malaria leading to different complications. Beyond the development of cerebral malaria, impairment of renal function is a mortality indicator in infected patients. Treatment with antimalarial drugs can increase survival, however the long-term effects of malaria on renal disease, even after treatment with antimalarials, are unknown. The aim of this study was to evaluate the effect of antimalarial drug treatment on renal function in a murine model of severe malaria and then evaluate kidney susceptibility to a second renal insult. Initially, mice infected with Plasmodium berghei ANKA achieved 20% parasitemia on day 5 post infection, which was completely abolished after treatment with 25 mg/kg artesunate and 40 mg/kg mefloquine. The treatment also decreased plasma creatinine levels by 43% and partially reversed the reduction in the glomerular filtration rate induced by infection. The urinary protein/creatinine ratio, collagen deposition, and size of the interstitial space decreased by 75%, 40%, and 20%, respectively, with drugs compared with untreated infected animals. In infected-treated mice that underwent a second renal insult, the plasma creatinine level decreased by 60% and the glomerular filtration rate increased compared with infected animals treated only with antimalarials. The number of glomerular cells, collagen deposition and the size of the interstitial space decreased by 20%, 39.4%, and 41.3%, respectively, in the infected group that underwent a second renal insult compared with the infected-treated groups. These functional and structural data show that renal injury observed in a murine model of severe malaria is partially reversed after antimalarial drug treatment, making the kidney less susceptible to a second renal insult.
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Thiago P
authors.initials: TP
authors.lastname: Abreu
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Leandro S
authors.initials: LS
authors.lastname: Silva
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Takiya
authors.affiliation: Instituto de Tecnologia em Fármacos, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Mariana C
authors.initials: MC
authors.lastname: Souza
authors.affiliation: Instituto de Tecnologia em Fármacos, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Henriques
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil; Instituto Nacional para Pesquisa Translacional em Saúde e Ambiente na Região Amazônica, Conselho Nacional de Desenvolvimento Científico e Tecnológico/MCT, Rio de Janeiro, RJ, Brazil.
authors.forename: Ana Acacia S
authors.initials: AA
authors.lastname: Pinheiro
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil; Instituto Nacional de Ciência e Tecnologia em Biologia e Bioimagem, Conselho Nacional de Desenvolvimento Científico e Tecnológico/MCT, Rio de Janeiro, RJ, Brazil.
authors.forename: Celso
authors.initials: C
authors.lastname: Caruso-Neves
mesh_terms: D058186:Acute Kidney Injury / Q000469:parasitology* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000494:pharmacology*; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D007672:Kidney Cortex / Q000378:metabolism / Q000473:pathology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology; D008288:Malaria / Q000150:complications* / Q000188:drug therapy*; D008297:Male; D051379:Mice; D018512:Parasitemia / Q000188:drug therapy / Q000473:pathology; D010962:Plasmodium berghei / Q000187:drug effects; D020011:Protective Agents / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D000962:Antimalarials; D020011:Protective Agents; D003094:Collagen
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