Laboratory Investigation

Kidney International (1993) 44, 774–788; doi:10.1038/ki.1993.312

Interstitial fibrosis in obstructive nephropathy

Atul K Sharma1, S Michael Mauer1, Youngki Kim1 and Alfred F Michael1

1Department of Pediatrics, Division of Pediatric Nephrology, University of Minnesota, Minneapolis, Minnesota, USA

Correspondence: Atul K Sharma MD, Montreal Children's Hospital, Room E.222, 2300 Rue Tupper, Montreal, Canada H4A 1P3.

Received 4 January 1993; Revised 26 April 1993; Accepted 24 May 1993.

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Abstract

Interstitial fibrosis in obstructive nephropathy. Interstitial fibrosis and tubular basement membrane (TBM) thickening are evident within 16 days of unilateral ureteral obstruction (UUO) in the rabbit, and resemble the changes previously reported in hydronephrotic human kidneys. The cortical interstitial volume fraction in this rabbit model at 16 days is 43.3 plusminus 6.1% (plusminus 1 SD) in UUO kidneys, 4.9 plusminus 3.1% in contralateral kidneys (CLK), and 2.8 plusminus 0.8% in kidneys from sham-operated animals (ANOVA, P < 0.0001). Immunohistochemically, UUO is associated with increased interstitial collagens I and III, fibronectin, heparan sulfate proteoglycan and tubulointerstitial nephritis antigen. Aberrant collagen expression is also evident as interstitial collagen IV becomes prominent. Focal, peritubular accumulation of collagens I and III also appear to encircle the TBM. These changes are accompanied by an early, transient increase in renal cortical mRNA encoding the alpha1 monomers of collagens I, III and IV, implicating increased matrix synthesis in the pathogenesis of obstructive nephropathy. In situ hybridization localized increased expression of alpha1(I) and alpha1(IV) mRNA to cells in the interstitial space, with clusters of alpha1(I) positive cells associated with dilated tubules, muscular arteries and the periglomerular interstitium.

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