Diabetic nephropathy is a major cause of
end-stage kidney disease (ESKD) in patients with type 1 and
type 2 diabetes throughout the world. In human glomeruli, expansion of diffuse mesangial matrices, exudative lesions and/or segmental nodular
sclerosis are pathological features of
diabetic nephropathy. There have been many reports on the pathogenesis and treatment of
type 2 diabetes using various animal models. It appears that KK-Ay mice, especially in terms of their immunohistological findings, are a suitable animal model for human type 2
diabetic nephropathy. Many compounds have been reported to be
advanced glycation end product (AGE) inhibitors such as
aminoguanidine,
angiotensin II receptor inhibitors and
pyridoxamine, and these are useful in therapeutic interventions for reducing AGEs.
Pyridoxamine ameliorates lipid peroxidation and
insulin resistance in KK-Ay mice. Combination
therapy with
angiotensin converting
inhibitors (ACE-I) and
angiotensin II type 1 receptor blockers (ARB), including an ARB and
1,25-dihydroxyvitamin D3, i.e.
anti-hypertensive and anti-
reactive oxygen species effects, or with
eicosapentaenoic acid (EPA), i.e. anti-microinflammation effect, have shown efficacy in the treatment of
diabetic nephropathy in KK-Ay mice. It appears that KK-Ay mice are a useful spontaneous animal model for the evaluation of pathogenesis and treatment in patients with type 2
diabetic nephropathy.