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Autonomic Renal Denervation Ameliorates Experimental Glomerulonephritis

Roland Veelken^*, Eva-Maria Vogel^*, Karl Hilgers^*, Kerstin Amann, Andrea Hartner, Gabriele Sass, Winfried Neuhuber^|| and Gisa Tiegs

^* Department of Nephrology and Hypertension, Institute of Pathology, Children and Youth Hospital, Institute of Experimental and Clinical Pharmacology and Toxicology, and ^|| Institute of Anatomy I, University of Erlangen-Nuremberg, Erlangen, Germany

Correspondence: Prof. Gisa Tiegs, Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, Fahrstrasse 17, D-91054 Erlangen, Germany. Phone: +4991318522883; Fax: +4991318522774; E-mail: tiegs{at}pharmakologie.uni-erlangen.de

Received for publication May 9, 2007. Accepted for publication February 14, 2008.

Increasing evidence indicates that inflammation of visceral organs is significantly affected by the autonomic nervous system. Such neuroimmune interactions have not been studied in the kidney. Here, we show that the rat kidney is innervated by both tyrosine hydroxylase–positive sympathetic efferent nerve fibers and calcitonin gene-related peptide–positive primary afferent nerve fibers, both of which are found in proximity to macrophages and dendritic cells. Complete surgical bilateral renal denervation was performed 2 d before glomerulonephritis was induced by injecting the monoclonal anti–Thy-1.1 antibody OX-7. Denervation significantly reduced albuminuria, mesangiolysis, formation of microaneurysms, deposition of glomerular collagen IV, and expression of TGF-β compared with sham-operated controls. Accordingly, inflammation, identified by accumulation of interstitial macrophages and renal expression of TNF-, and mesangial cell proliferation were significantly reduced. These findings indicate that autonomic renal denervation ameliorates and, by inference, innervation exacerbates acute inflammation in the kidney; therefore, neurotransmitters or neuropeptides and their receptors might represent novel targets for the treatment of acute glomerulonephritis.

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Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673