Long-term anti-glomerular basement membrane disease in the rat: A model of chronic glomerulonephritis with nephrosis, hypertension and progressive renal failure

Ping Fu, Tara Robertson, Prudence Hill, Greg Tesch, David J. Nikolic-Paterson, Robert Charles Atkins, Steven J. Chadban

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Current experimental models of glomerulonephritis focus on the acute phases of renal injury. Models replicating the features of human glomerulonephritis, including hypertension, proteinuria, hyperlipidaemia, renal fibrosis and renal failure, are lacking. The aim of this experiment was to define a rat model of glomerulonephritis that replicates the features of progressive glomerulonephritis in humans. Passive accelerated antiglomerular basement membrane disease was induced in inbred Sprague-Dawley rats. Age-matched control rats received pre-immunisation, but were given saline rather than nephrotoxic serum. Groups of diseased rats (n = 4-6) were killed at 4, 6 and 7 weeks, and tissues were extracted for histological assessment. Diseased rats developed renal failure over 7 weeks (91% reduction in creatinine clearance vs controls at week 7, P < 0.001). Proteinuria reached a plateau from week 2 to week 7 (269.1 ± 107.9 mg/24 h vs 1.00 ± 0.18 mg/mL for controls at week 7, P < 0.001). Diseased rats became hyperlipidaemic (108% increase in cholesterol vs control, P < 0.05) and hypertensive (38% increase in systolic blood pressure vs controls, P < 0.001). Histology revealed progressive renal fibrosis and scarring, with fibrocellular crescent formation (93% of glomeruli by week 7), glomerulosclerosis and tubulointerstitial damage. α-Smooth muscle actin expression and interstitial matrix (collagen III) deposition increased progressively. Urinary transforming growth factor-β excretion was increased by over eightfold versus controls. This model of passive accelerated antiglomerular basement membrane disease simulates many clinical and pathological features of chronic glomerulonephritis in humans, and may provide a good model to test new therapies.

Original languageEnglish
Pages (from-to)145-154
Number of pages10
JournalNephrology
Volume7
Issue number3
DOIs
Publication statusPublished - 23 Sep 2002

Keywords

  • Anti-glomerular basement membrane disease
  • Crescentic glomerulonephritis
  • Macrophage
  • Progression

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