Cytokine-mediated regulation of renal urea transporters during sepsis
© BioMed Central Ltd 2007
Published: 26 September 2007
The pathogenesis of endotoxemic tubular dysfunction with failure in urine concentration is poorly understood. Urea plays an important role in the urinary concentrating mechanism and expression of the urea transporters UT-A1, UT-A2, UT-A3, UT-A4 and UT-B is essential for tubular urea reabsorption. The present study attempts to assess the regulation of renal urea transporters during severe inflammation in vivo.
Materials and methods
By agreement of the animal protection committee C57BL/6J, mice were injected with lipopolysaccharides (LPS, 10 mg/kg) or proinflammatory cytokines. Hemodynamic, renal parameters and the expression of renal urea transporters were investigated. To clarify the role of cytokines and renal ischemia in the regulation of renal urea transporters, experiments were performed with cytokine knockout mice, mice treated with low-dose LPS (1, 5 mg/kg) as a sepsis model without induction of hypotension, glucocorticoid-treated mice, and mice with renal artery clipping serving as a model for renal ischemia.
Results and discussion
Our findings demonstrate downregulation of renal urea transporters that probably accounts for tubular dysfunction during sepsis. Furthermore, they suggest that downregulation of renal urea transporters during LPS-induced acute renal failure is mediated by proinflammatory cytokines and is independent from renal ischemia due to sepsis-induced hypotension.
Supported by grants from the German Research Foundation (SFB 699).