Leflunomide attenuates renal injury in 5/6 renal ablation in rats

Objective To investigate the effect of leflunomide on renal fibrosis in 5/6 renal ablation in rats.Methods The rats were randomly divided into 2 groups: Sham group (n=10) and 5/6 nephrectomy group (n=30).Nine rats in the group that had 5/6 nephrectomy died during surgery or in the following 48 hours.In the third day after surgery 5/6 nephrectomized rats were randomly subdivided in two groups(LEF 5 mg.kg-1.d-1 by daily gastric gavage,n=11 and model(Nx) group,n=10).Nx and Sham rats received equal volume of water by daily gavage.All rats were allowed free access to food and water.In eight weeks after the leflunomide treatment,the following studies were performed in every group.All of the items such as body weight,24-hours urinary protein,serum creatinine(Scr) were measured.Renal tissues of three groups were observed with light microscope after periodic acid-Schiff (PAS) and Masson staining.Immunohistochemical staining was used to estimate the expression of α-smooth muscle actin(α-SMA) in renal cortex,the results were analyzed semi-quantitatively with pathological image analysis system. Results Leflunomide treatment prevented the progressive increment in serum creatinine and the proteinuria observed in the 5/6 nephrectomized rats during the eight weeks of observation (P0.05).The degree of weight gain was comparable in the LEF-treated and sham-operated rats,whereas weight gain was less in untreated 5/6 nephrectomized rats than that in the above two groups (P0.05).Expression of α-SMA was increasingly strong in the glomeruli,tubules,and interstitium of remnant kidneys in Nx rats during eight weeks.Their expression was reduced significantly with leflunomide treatment (P0.05).The histologic observations showed severe mesangial expansion,extensive capillary loops occusion,tubular atrophy and interstitial fibrosis in eight weeks in Nx group,as well as severe mesangial expansion,extensive capillary loops occusion,glomerulosclerosis,tubular atrophy and interstitial fibrosis,but the abnormal changes were alleviated in LEF group. Conclusion Leflunomide treatment markedly inhibits proliferation of myofibroblast,it has protective effect on kidney via preventing and delaying the renal fibrosis.