Urinary biomarkers for the identification of cyclosporin A-induced renal injury

• Grant number: 09/17100-2
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2010
• End date: March 31, 2012
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Emmanuel de Almeida Burdmann
• Grantee: Emmanuel de Almeida Burdmann
• Host Institution: Faculdade de Medicina de São José do Rio Preto (FAMERP). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São José do Rio Preto , SP, Brazil

Abstract

The establishment of biomarkers to determine the development of early renal injury may be useful in the monitoring of cyclosporin A (CsA) treatment. Thus, the aim of this study is to investigate the urinary biomarkers for the identification of cyclosporin A-induced renal injury in rats, correlating with the development of hemodynamic and structural changes, both in acute and chronic phases. Munich-Wistar male rats weighing approximately 250 g will be distributed in 6 groups. The CsA nephrotoxicity will be studied in 3 time points: 7, 14 and 21 days with one treated CsA group (15 mg/Kg/day) and one control group (vehicle) with 8 animals each. At the end of treatments, the animals will be allocated into metabolic cages and after 24 hours will be submitted to surgery and studies of glomerular filtration rate (inulin clearance) and renal blood flow. The blood CsA will be determined as well as blood and urinary creatinine, sodium and potassium, hematocrit, urinary osmolality and microalbuminuria. The kidneys will be removed and used in the studies for morphometry (tubulointerstitial fibrosis) and immunohistochemistry for macrophage, osteopontin, TGF-², fibronectin, podocin, collagen IV, alpha-SMA (alpha smooth muscle actin) and vimentin. Elisa assays will be used to quantification of urinary markers: podocin to glomerular injury marker; KIM-1 (kidney injury molecule-1) to proximal tubule injury marker and acute injury; NGAL (neutrophil gelatinase-associated lipocalin) to acute injury marker; fibronectin, TGF-² and collagen IV to fibrosis marker; MCP-1, osteopontin, TNF-alpha and IL-6 to macrophage and inflammation markers. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CARLOS, CARLA PATRICIA; SONEHARA, NATHALIA MARTINS; OLIANI, SONIA MARIA; BURDMANN, EMMANUEL A.. Predictive Usefulness of Urinary Biomarkers for the Identification of Cyclosporine A-Induced Nephrotoxicity in a Rat Model. PLoS One, v. 9, n. 7, JUL 29 2014. (09/17100-2)