In addition, diabetic, hypertensive Akita+/− Ren+/− mice were noted to have advanced glomerulosclerosis with significantly expanded mesangial matrix, as compared to wild type Akita−/− Ren−/− controls, as well as diabetic, normotensive Akita+/− Ren−/− mice (Fig. 2a,b). Here, REN is linked to glomerulosclerosis.