The DPP4 inhibitor linagliptin ameliorated renal injury and accelerated resolution in a rat model of crescentic nephritis

Background and Purpose Dipeptidyl peptidase 4 (DPP-4) inhibitors are a class of oral glucose-lowering drugs used in the treatment type 2 diabetes. In pilot study using human kidney biopsies, we observed high DPP-4 expression early crescent formation. This glomerular lesion occurs different diseases is hallmark pathogenesis renal dysfunction. Therefore, investigated potential involvement nephritis induced by anti-glomerular basement membrane (GBM) antibody rats. Experimental Approach Linagliptin vehicle were to treat anti-GBM 2- 8-week regimen, that either preventive or therapeutic (treatment started 7 days weeks after disease induction). Kidney function, morphologic changes, inflammation fibrosis monitored. Key Results long-term experiment, linagliptin nephritic rats significantly reduced number crescents, glomerulosclerosis, tubular injury fibrosis, compared with those untreated Both regimes lowered Pax8+ cells on tuft nephritis, indicating accelerated resolution cellular crescents. The did not change but podocyte stress both groups. Therapeutic intervention resulted weaker amelioration Week 8 than intervention. Conclusion Implications inhibition ameliorates rat model anti-GBM, only secure therapy diabetes also can improve healing non-diabetic disease.