Fig. 5
Simulated effects of pressure-induced nephron injury and uninephrectomy on disease progression in db/db mice. Solid lines: simulations (black: non-db, light blue – db/db non-UNX with injury effects turned off, dark blue–db/db non-UNX with injury effects turned on, red–db/db UNX with injury effects turned on). Points: experimental data (black non-db, blue – db/db, red – db/db UNX). See Fig. 2 for data references. In db/db non-UNX mice, when injury effects were turned on, elevated glomerular pressure (a) caused Kf to peak and then begin to decrease (b), as the effect of glomerular hypertrophy saturated while the effect of glomerosclerosis grew; elevated glomerular pressure also drove a decrease in nephron number (c) and an increase in glomerular albumin sieving. GFR (e) increased over time but eventually began to decrease slowly around week 10, while glomerular pressure (a) and UAER (f) progressively increased, in agreement with experimental data. When UNX was simulated at 8 weeks, GFR initially dropped but recovered before beginning to progressively decline. This progression was driven by a further increase in glomerular pressure, and an accelerated rate of glomerulosclerosis (Kf decrease) and nephron loss
