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Interstitial fibrosis in obstructive nephropathy

A K Sharma1, S M Mauer, Y Kim

  • 1Department of Pediatrics, University of Minnesota, Minneapolis.

Kidney International
|October 1, 1993
PubMed
Summary
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Unilateral ureteral obstruction (UUO) in rabbits causes kidney fibrosis and tubular basement membrane thickening. This obstructive nephropathy involves increased collagen synthesis and interstitial matrix accumulation.

Area of Science:

  • Nephrology
  • Pathology
  • Molecular Biology

Background:

  • Interstitial fibrosis and tubular basement membrane (TBM) thickening are key features of obstructive nephropathy.
  • These changes are observed in human hydronephrotic kidneys and can be modeled in animals.

Purpose of the Study:

  • To investigate the early molecular and cellular changes in a rabbit model of unilateral ureteral obstruction (UUO).
  • To elucidate the role of matrix synthesis in the pathogenesis of obstructive nephropathy.

Main Methods:

  • Unilateral ureteral obstruction (UUO) in rabbits.
  • Measurement of cortical interstitial volume fraction.
  • Immunohistochemistry for interstitial collagens, fibronectin, and proteoglycans.
  • Analysis of renal cortical mRNA expression for collagens using RT-PCR and in situ hybridization.

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Main Results:

  • UUO kidneys showed significant interstitial volume expansion (43.3%) compared to contralateral (4.9%) and sham (2.8%) kidneys at 16 days.
  • Increased expression of interstitial collagens I, III, IV, fibronectin, and heparan sulfate proteoglycan was observed.
  • Early, transient increase in renal cortical mRNA for collagen alpha 1 monomers (I, III, IV) indicated increased matrix synthesis.
  • In situ hybridization localized collagen mRNA expression to interstitial cells, particularly around dilated tubules and vessels.

Conclusions:

  • Early interstitial fibrosis and TBM thickening occur rapidly after UUO in rabbits.
  • Increased synthesis of interstitial collagens and matrix proteins plays a crucial role in the pathogenesis of obstructive nephropathy.
  • This rabbit model effectively recapitulates key pathological features of human obstructive kidney disease.