Interferon-γ improves renal interstitial fibrosis and decreases intrarenal vascular resistance of hydronephrosis in an animal model

Urology. 2011 Mar;77(3):761.e8-13. doi: 10.1016/j.urology.2010.10.015. Epub 2011 Jan 8.

Abstract

Objectives: To investigate the effect of interferon (IFN)-γ administration on renal interstitial fibrosis (RIF) and intrarenal vascular resistance of diseased kidneys in a reversible unilateral ureteral obstruction (RUUO) animal model.

Methods: Thirty-six male Sprague-Dawley rats were randomly divided into three groups: RUUO with intramuscular IFN-γ treatment (400 IU/d; RUUO + IFN), RUUO with vehicle treatment, and sham operation. RUUO was induced by clamping the left ureter using a small polyethylene tube. The obstruction was reversed seven days after the operation by removing the tube. Six animals in each group were killed at days 7 and 14. The intrarenal resistive index (RI) of diseased kidneys was measured by colored Doppler flow imaging. RIF was evaluated using Masson's trichrome staining.

Results: The obstruction was successfully reversed in all animals. At day 7, the RIF scores were 32.1 ± 3.1 and 40.3 ± 3.1 in the RUUO + IFN group and the RUUO group, respectively. The RI increased by 87% in the RUUO group and by 64% in the RUUO + IFN group compared with sham. At day 14, the RIF scores decreased to 24.6 ± 3.9 in the RUUO + IFN group, but increased to 50.8 ± 4.4 in the RUUO group. The increase of RI was reduced to 64% in the RUUO group and to 20% in the RUUO + IFN group. Ureteral obstruction induced few lesions in the contralateral kidneys, and IFN-γ administration had no significant effect on them, although it exerted an antifibrotic effect on the obstructed kidneys.

Conclusions: IFN-γ administration restored or preserved renal histology and hemodynamics in an animal model of renal fibrosis after surgical reversal of hydronephrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Flow Velocity / drug effects
  • Disease Models, Animal
  • Fibrosis
  • Hydronephrosis / etiology
  • Hydronephrosis / pathology*
  • Hydronephrosis / physiopathology
  • Interferon-gamma / pharmacology*
  • Kidney / drug effects
  • Kidney / pathology*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Renal Circulation / drug effects*
  • Ureteral Obstruction / complications
  • Ureteral Obstruction / pathology
  • Ureteral Obstruction / physiopathology
  • Vascular Resistance / drug effects*

Substances

  • Interferon-gamma