INTERSTITIAL FIBROSIS IN OBSTRUCTIVE NEPHROPATHY

Interstitial fibrosis and tubular basement membrane (TBM) thickening a re evident within 16 days of unilateral ureteral obstruction (UUO) in the rabbit, and resemble the changes previously reported in hydronephr otic 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, f ibronectin, heparan sulfate proteoglycan and tubulointerstitial nephri tis antigen. Aberrant collagen expression is also evident as interstit ial 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 en coding the alpha1 monomers of collagens I, III and IV, implicating inc reased matrix synthesis in the pathogenesis of obstructive nephropathy . In situ hybridization localized increased expression of alpha1(I) an d alpha1(IV) mRNA to cells in the interstitial space, with clusters of alpha(I) positive cells associated with dilated tubules, muscular art eries and the periglomerular interstitium.