Journal of the American Society of Nephrology
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Published ahead of print on January 16, 2008
Journal of the American Society of Nephrology
© 2008 American Society of Nephrology
doi: 10.1681/ASN.2007080862
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Received August 6, 2007
Accepted on August 9, 2007

BRIEF REVIEWS

Generation and Evolution of Atubular Glomeruli in the Progression of Renal Disorders

Robert L. Chevalier 1 and Michael S. Forbes

Department of Pediatrics, University of Virginia, Charlottesville, Virginia


1 To whom correspondence should be addressed. E-mail: RLC2M{at}virginia.edu.


   Abstract

Functional nephrons can be lost through a process of glomerulotubular disconnection. Progressive development of atubular glomeruli seems to play a major role in a number of renal disorders, including glomerular diseases, ascribed to injury to the glomerulotubular junction as a result of proteinuria; however, formation of atubular glomeruli is even more common in tubulointerstitial disorders, such as obstructive nephropathy. Toxic nephropathy is also associated with the formation of atubular glomeruli, suggesting susceptibility of the glomerulotubular junction to toxic injury. Narrowing or other abnormalities of the glomerulotubular junction are described as precursors of glomerulotubular disconnection. Cystinosis represents a dramatic example of progressive injury to the glomerulotubular junction, with formation of the "swan-neck deformity" following degenerative tubular cell changes attributable to apoptosis. Significant numbers of atubular glomeruli have been reported in chronic pyelonephritis and renal allograft rejection; this suggests interstitial inflammation as a stimulus for the formation of atubular glomeruli. Because of difficulties in morphologic recognition, it is likely that glomerulotubular disconnection is an underappreciated mechanism in the progression of renal disease. A better understanding of the vulnerability of the glomerulotubular junction and its protection from injury should lead to better strategies for preserving renal function in many nephropathies.







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