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Pharmacology

Immune-Mediated Nephropathy Model

2017-02-10
18662
Kunming, China, February 10, 2017

Anti-glomerular basement membrane (GBM) glomerulonephritis accounts for 20% of all cases of rapidly progressive glomerulonephritis (GN) in the adult human population. End-stage renal disease develops in 40-70% of patients who have nephritis mediated by anti-GBM antibodies.  Recent investigations have proposed the concept that the immune system plays a role in the mechanisms of diabetic nephropathy.  Several components of the immune system including cytokines and resident chemokines, macrophage recruitment, T lymphocytes, and immune complex deposition that have been implicated in other glomerular diseases are now explored for their association with diabetic nephropathy.  Furthermore, anti-GBM nephritis shares several common downstream molecular mechanisms and targets with lupus nephritis making the anti-GBM nephritis animal model another relevant and effective model for lupus nephritis disease translation.


At KBI, anti-GBM GN can be induced in the cynomolgus monkey model by immunization with type IV collagen. The cynomolgus nephritis model provides translational value to examine cellular and immune-mediated mechanisms of glomerulonephritis and pathogenesis of crescents, mesangial hypercellularity, interstitial fibrosis, and proteinuria. Furthermore, the cynomolgus macaque models of glomerulonephritis and diabetic nephropathy demonstrate comparable albuminuria, immune-mediated inflammatory targets, and renal morphological changes with human patients, suggesting that these common biomarkers and endpoints are useful for evaluating disease severity and treatment efficacy.


·  Normal cynomolgus monkeys
·  Intact or Unilateral nephrectomy
·  Induction: Nephritogenic Type IV Collagen
·  Endpoints:
      ·  24-hour urine proteinuria
      ·  Measurement of anti-NC1 antibody titer in serum and urine samples
      ·  GFR measurement by inulin clearance
      ·  Kidney biopsy
           ·  Standard histomorphology: H&E, PAS and PAM staining
           ·  IF staining for anti-monkey IgG, IgA and C3
           ·  IHC staining for α-SMA and CD68

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