Rosiglitazone reverses tenofovir-induced nephrotoxicity


Autoria(s): LIBORIO, Alexandre B.; ANDRADE, Lucia; PEREIRA, Leonardo V. B.; SANCHES, Talita R. C.; SHIMIZU, Maria H.; SEGURO, Antonio C.
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

19/10/2012

19/10/2012

2008

Resumo

Tenofovir disoproxil fumarate (TDF) is a first-line drug used in patients with highly active retroviral disease; however, it can cause renal failure associated with many tubular anomalies that may be due to down regulation of a variety of ion transporters. Because rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist induces the expression of many of these same transporters, we tested if the nephrotoxicity can be ameliorated by its use. High doses of TDF caused severe renal failure in rats accompanied by a reduction in endothelial nitric-oxide synthase and intense renal vasoconstriction; all of which were significantly improved by rosiglitazone treatment. Low-dose TDF did not alter glomerular filtration rate but produced significant phosphaturia, proximal tubular acidosis, polyuria and a reduced urinary concentrating ability. These alterations were caused by specific downregulation of the sodium-phosphorus cotransporter, sodium/hydrogen exchanger 3 and aquaporin 2. A Fanconi`s-like syndrome was ruled out as there was no proteinuria or glycosuria. Rosiglitazone reversed TDF-induced tubular nephrotoxicity, normalized urinary biochemical parameters and membrane transporter protein expression. These studies suggest that rosiglitazone treatment might be useful in patients presenting with TFV-induced nephrotoxicity especially in those with hypophosphatemia or reduced glomerular filtration rate.

FAPESP, Foundation for the Support of Research in the state of Sao Paulo

LIM, Laboratory for Medical Research

FFM, School of Medicine Foundation

CNPq, National Council for Scientific and Technological Development

Identificador

KIDNEY INTERNATIONAL, v.74, n.7, p.910-918, 2008

0085-2538

http://producao.usp.br/handle/BDPI/26888

10.1038/ki.2008.252

http://dx.doi.org/10.1038/ki.2008.252

Idioma(s)

eng

Publicador

NATURE PUBLISHING GROUP

Relação

Kidney International

Direitos

restrictedAccess

Copyright NATURE PUBLISHING GROUP

Palavras-Chave #reverse transcriptase inhibitors #vasodilator agents #adenine/tenofovir #thiazolidinediones/rosiglitazone #kidney failure #acute #NEPHROGENIC DIABETES-INSIPIDUS #RENAL-FAILURE #FANCONI-SYNDROME #RECEIVING TENOFOVIR #DISOPROXIL FUMARATE #NA+ TRANSPORTERS #HIV-INFECTION #RATS #THERAPY #SAFETY #Urology & Nephrology
Tipo

article

original article

publishedVersion