Journal of the American Society of Nephrology
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Published ahead of print on January 23, 2008
J Am Soc Nephrol 19: 538-546, 2008
© 2008 American Society of Nephrology
doi: 10.1681/ASN.2007040513

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BASIC RESEARCH

Acute Rejection Modulates Gene Expression in the Collecting Duct

Bayram Edemir, Stefan Reuter, Reka Borgulya, Rita Schröter, Ute Neugebauer, Gert Gabriëls and Eberhard Schlatter

Medizinische Klinik und Poliklinik D, Experimentelle Nephrologie, Universitätsklinikum Münster, Münster, Germany

Correspondence: Dr. Bayram Edemir, Medizinische Klinik und Poliklinik D, Experimentelle Nephrologie, Domagkstraβe 3a, 48149 Münster, Germany. Phone: 49-251-83-56912; Fax: +49-251-83-56973; E-mail: edemir{at}uni-muenster.de

Received for publication April 28, 2007. Accepted for publication October 24, 2007.

Kidney transplantation, especially when associated with acute rejection, leads to changes in the expression of many genes, including those encoding solute transporters and water channels. In a rat model of acute rejection after allogeneic renal transplantation, impaired renal function, increased urine volume, and increased fractional excretion of sodium were observed. Gene array analysis revealed that these findings were associated with significant downregulation of water channels (aquaporin-1, -2, -3, and -4) and transporters of sodium, glucose, urea, and other solutes. In addition, changes in expression of various receptors, kinases, and phosphatases that modulate the expression or activity of renal transport systems were observed. Syngeneic transplantation or treatment with cyclosporine A following allogeneic transplantation did not impair graft function but did lead to the downregulation of aquaporin-1, -3, and -4 and several solute transporters. However, expression of aquaporin-2 and the epithelial sodium channel did not change, suggesting that the downregulation of these transporters following allogeneic transplantation is rejection-dependent. In conclusion, changes in gene expression may explain the impaired handling of solute and water after allogeneic transplantation, especially during acute rejection. Treatment with cyclosporine A improves the regulation of solute and water by preventing the downregulation of aquaporin-2 and epithelial sodium channel, even though many other transporter genes remain downregulated.







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