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 ± 6.1% (± 1 SD) in UUO kidneys, 4.9 ± 3.1% in contralateral kidneys (CLK), and 2.8 ± 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 α1 monomers of collagens I, III and IV, implicating increased matrix synthesis in the pathogenesis of obstructive nephropathy. In situ hybridization localized increased expression of α1(I) and α1(IV) mRNA to cells in the interstitial space, with clusters of α1(I) positive cells associated with dilated tubules, muscular arteries and the periglomerular interstitium.
Bibliographical noteFunding Information:
Dr. Sharma was supported by the Duncan L. Gordon Fellowship from the Hospital for Sick Children Foundation, Toronto, Canada. This work was supported by the Viking Children's Fund, Minneapolis, Minnesota, and N.I.H. grant Al 10704. The authors acknowledge the