Gamma-secretase inhibitors improve nephropathy. MRL-lpr mice were randomized to treatment with DAPT or vehicle. Eight weeks after starting therapy, mice were killed and kidneys were assessed for disease. Kidney disease burden was scored 0 to 5 on 4 measures: (1) nephropathy; (2) glomerulonephritis; (3) cortical lymphoid proliferation (LP); and (4) medullary lymphoid proliferation (LP). Higher scores represent more severe disease. (A) Average total cumulative score for 4 control and 6 treated animals. Colored portions of the bars depict the individual disease measures. Treated mice demonstrated a reduction in all 4 disease parameters compared with control and a statistically significant reduction in total kidney disease (P = .007). Error bars depict SD of total kidney disease score. (B-E) Kidney pathology by H&E stain. Treated animals have healthy kidneys with limited disease (B,C). In contrast, control animals have pronounced lymphocytic infiltration in cortex (D) and medulla (E). In addition, control animals have damaged glomeruli and proteinaceous material in renal tubules. Images were captured using a Zeiss Axiovert 40C light microscope (Carl Zeiss, Thornwood, NJ) equipped with an apochromatic 10×/0.25 NA objective lens and a Nikon 995 camera (Nikon, Melville, NY).