Diabetic nephropathy (DN) occurs in approximately 20-40% of the type 2 diabetes (T2D) global population. It has always been a challenge to find translatable, reliable and robust animal disease models for diabetic nephropathy − but the monkey model of diabetes with the progressive development of complications that resembles all the disease characteristics in humans can be considered as one of the most clinically translatable animal disease model for diabetic nephropathy.
Anti-glomerular basement membrane (GBM) glomerulonephritis accounts for 20% of all cases of rapidly progressive glomerulonephritis (GN) in adult humans. The end-stage renal disease develops in 40-70% of patients who have nephritis mediated by anti-GBM antibodies. Multiple immune components including cytokines and resident chemokines, macrophage recruitment, T lymphocytes, and immune complex deposition 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.
KBI has the following models of immune-induced nephritis and assessment tools:
· Normal cynomolgus monkeys
· Intact or Unilateral nephrectomy
· Induction: Nephritogenic Type IV Collagen
· Endpoint measurements: 24-hour urine proteinuria, Measurement of anti-NC1 antibody titer in serum and urine sample and GFR measurement by inulin clearance
· Kidney biopsy for: Standard histomorphology (H&E, PAS and PAM staining), IF staining for anti-monkey IgG, IgA and C3 and IHC staining for α-SMA and CD68