3.1.1. Kidney pathophysiology: key features that need to be
represented in animal models
Diabetic nephropathy is a progressive complication of DM, a leading
cause of end-stage renal failure globally. A main clinical feature that
presents in both Type1 and Type2 diabetic patients is albuminuria where
the first manifestation typically occurs as microalbuminuria, defined as
albumin excretion of 30-299mg in 24 hours. Over time, microalbuminuria
progresses to proteinuria, defined as albumin excretion of over 500mg in
24 hours leading to overt diabetic nephropathy[104]. Hyperglycaemia
acts as the major driving force of the progression to diabetic
nephropathy with the generation of ROS, formation of AGEs, and the
activation of polyol and PKC pathways all contributing to glomerular
damage. The downstream consequences include inflammation, thickening of
the glomerular basement membrane and microaneurysm formation[105].
In addition, accumulation of extracellular matrix proteins such as
collagens and fibronectin replaces healthy renal architecture, leading
to mesangial expansion and reduction of filtration surface area, which
in turn is further disrupted by the thickening of glomerular basement
membranes[106].