Effects of 5/6 nephrectomy and high-protein diet on glomerular and tubular injuries in mice

Abstract Numerous animal models of chronic kidney disease (CKD) have been developed. However, mice are relatively resistant to kidney injury. We aimed to evaluate the effects of high-protein diet (HPD) loading and 5/6 nephrectomy (Nx) in a susceptible strain of mice (129/Sv) over a long-term period. 129/Sv mice were divided into three groups: sham surgery (sham) + normal diet (ND) group, sham + HPD group, and 5/6 Nx + HPD group. Blood pressure, kidney function, and kidney tissue injury were compared longitudinally for 12 weeks among the three groups. The 5/6 Nx + HPD group displayed blood pressure elevation, kidney function decline, severe albuminuria, glomerular injury, and tubular injury compared with the sham + ND and sham + HPD groups. However, there was no significant difference in kidney injuries between the sham + ND and sham + HPD groups. Furthermore, the 5/6 Nx + ND group was added in comparison with the 5/6 Nx + HPD group. The glomerular injury was significantly exacerbated in the 5/6 Nx + HPD group than in the 5/6 Nx + ND group. These results indicate that HPD loading alone has little effect on kidney injury, while it exacerbates glomerular injury in the remnant kidney model.