Long-term TWEAK administration increases disease progression in ADPKD. TWEAK was administered after Pkd1 inactivation, every 48 hours, until euthanasia at p45 (long term). (A) Representative hematoxylin and eosin–stained kidney sections harvested at p45 in control (n=6) and TWEAK-treated (n=6) groups. Schematic representation of the experimental design in Supplemental Figure 1C. Scale bars, 2 mm (upper panel) and 100 µm (lower panel). TWEAK increases (B) BUN, the (C) kidney/body weight ratio, (D) renal cystic index, and (E) cyst number. (F) Kaplan–Meier survival plots over time. Mice exposed to TWEAK had decreased survival compared with control mice. (G) Weight of control and TWEAK-exposed mice: TWEAK treatment slowed weight gain. Bars represent means±SEM. *P<0.05, **P<0.01.