We performed this study in order to investigate the effect of direct renin inhibition on an experimental animal model with nephrotoxic serum nephritis and tried to give useful information for clinical research and renin inhibitor treatment.

Thirty BALB/c 6-week-old male mice were divided into 4 groups: control group (CO, n=5), control-treatment group with aliskiren (CT, n=5), disease group (DO, n=10), and disease treatment group with aliskiren (DT, n=10). Nephritis was induced by an intravenous injection of 0.25 mg/g weight of rabbit anti-GBM immunoglobulin G. Model 2002 Alzet mini-osmotic pumps (Durect Corp.) for aliskiren infusion were implanted into CT and DT. Each group strain was sacrificed serially one at a time on day 14. We estimated the protein-creatinine ratio in 12-hour-collected urine (UP/Cr) and measured the mesangial matrix score in the PAS-stained kidney of each strain.

One strain at CT and DT died on day 6 and 7, respectively. Each group strain was sacrificed serially at a time on day 10 because DO were seriously ill. The UP/Cr of each group is as follows: CO, 31.24±6.54 mg/mg, CT, 23.38±13.60 mg/mg, DO, 112.72±10.97 mg/mg, DT 114.07±32.30 mg/mg. There was no significant difference between DO and DT. The mesangial matrix score of each group was CO, 0.23±0.10; CT, 0.13±0.03; DO, 1.90±0.48; and DT, 1.28±0.41, respectively, and there was a significant difference between DO and DT in the extent of mesangial matrix expansion ( P =0.008).

We found that renin inhibition was able to suppress the mesangial matrix expansion in experimental mice with acute nephritis, although there were no significant differences in UP/Cr.