Figure 5.

Treatment with anti-TWEAK decreases renal cyst progression. (A) hematoxylin and eosin–stained, sagittal cross-sections of kidneys treated with anti-TWEAK (n=7 at p18, n=6 at p30) and control kidneys (n=6 at p18, n=6 at p30), euthanasia occurred at p18 and p30. Representative images with values within mean±1×SEM are shown. See Supplemental Figure 1C for experimental design. Scale bars, 2 mm (upper panel) and 100 µm (lower panel). (B) BUN, (C) kidney/body weight ratio, and (D) cystic index were significantly reduced in anti-TWEAK–treated mice at p18 and p30. (E) No significant differences in cyst number were observed at p30. (F) However, classification of the number of cysts by size in three groups, according to the size estimated by number of pixels, showed that the number of largest cysts (>750 pixels) decreased with treatment. (G) Representative images of immunofluorescence staining for specific nephron markers are shown, including proximal tubule (LTL, green) and collecting duct (DBA, red). Anti-TWEAK treatment slows enlargement of LTL⁺ and DBA⁺ cysts (Cy). *Cyst without specific markers; yellow arrow, dilated tubule; yellow arrowhead, tubule. Scale bars, 100 µm (upper panel) and 50 µm (lower panel). (H) Quantification of immunofluorescence cystic area. Anti-TWEAK treatment reduces cystic area of LTL⁺ and DBA⁺ cysts. (I) Kaplan–Meier survival plots of time. Treatment with anti-TWEAK increased survival (93% survival) compared with control and TWEAK-exposed mice. Bars represent means±SEM. *P<0.05, **P<0.01.