A novel mechanism of nephron loss in a murine model of crescentic glomerulonephritis.

Abstract

BACKGROUND Nephron loss is a major determinant of renal failure in glomerular diseases. The prevalent concept stresses the role of the toxicity of filtered proteins and/or of interstitial inflammation in tubular degeneration. However, whether that concept is compatible with the actual histopathological features of nephron loss has not been investigated specifically. METHODS We investigated the morphological aspects of tubular degeneration in crescentic glomerulonephritis in mice. Glomerulonephritis was induced by intravenous injection of anti-glomerular basement membrane antiserum in presensitized mice. Kidneys were fixed by perfusion and examined by light- and electron microscopy and by immunohistochemistry. RESULTS Tubular degeneration started with cellular hypotrophy in the proximal tubule. Hypotrophy appeared to follow obstruction of the initial proximal tubule by a cellular crescent. Whereas induction of intercellular adhesion molecule-1 (ICAM-1) was diffuse in glomerulonephritic mice, expression of CD44 and vascular cell adhesion molecule-1 (VCAM-1) appeared to be restricted to degenerating tubules. Interstitial inflammation developed in the vicinity of degenerating tubules. Inflammatory infiltration of tubules themselves was observed only in late stages of tubular degeneration. CONCLUSION In a similar manner as described earlier for focal segmental glomerulosclerosis, in crescentic glomerulonephritis nephron loss can be initiated by the progression of a glomerular lesion into the proximal tubule. Interstitial inflammation might be rather a consequence than the cause of tubular degeneration.

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@article{Hir2003ANM, title={A novel mechanism of nephron loss in a murine model of crescentic glomerulonephritis.}, author={Michel Le Hir and Val{\'e}rie Besse-Eschmann}, journal={Kidney international}, year={2003}, volume={63 2}, pages={591-9} }