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. 2018 Jul 19;128(10):4485–4500. doi: 10.1172/JCI99768

Figure 7. GS-444217 halts the progressive decline of renal function in a mouse model of DKD.

Figure 7

(A–E) Ten-week-old db/db eNOS–/– mice were fed standard rodent chow (vehicle) or chow containing GS-444217 (0.3% by weight) for 8 weeks. A separate group of untreated db/db eNOS–/– mice were euthanized at 10 weeks of age to establish baseline-disease parameters. (A) GFR was measured using inulin-FITC clearance in baseline mice (week 10) and in treated mice (week 18). (B) Proteinuria (urinary albumin to creatinine ratio [UACR]) was measured at weeks 10, 14, and 18. (C) A sclerosis injury score was calculated at 18 weeks on periodic acid–Schiff–stained kidneys averaging the lesion scores of 80–100 glomeruli per mouse using the following scoring system: 0, no lesion; 1, sclerosis of up to 25% of the glomerulus; 2, sclerosis of 25%–50%; 3, sclerosis of 50%–75%; and 4, sclerosis of >75% of the glomerulus. (D and E) Image analysis and graphed pathology scores of renal sections stained for collagen deposition (collagen IV) (D) or podocyte loss (Wilms tumor antigen [WT-1]) (E). Scale bars: 100 μm (C), 50 μm (E), or 30 μm (D). Data in A–E are mean ± SEM, n = 9–12; *P < 0.05 vs. 10-week baseline by unpaired t test, †P < 0.05 vs. vehicle (ANOVA with Bonferroni’s multiple-comparisons test).