Resistance to Tubulointerstitial Injury in a Mouse Remnant Kidney Model

Numerous animal models of CKD have been developed, but mice are relatively resistant to kidney injury. The remnant kidney model mimics progressive renal failure, and widely used in CKD research. The present study was performed to evaluate the effects of combined high-protein diet (HPD) loading and 5/6 nephrectomy (Nx) in a susceptible strain of mice (129/Sv). Mice underwent 5/6 Nx or sham surgery, then 2 weeks later were switched to an HPD, and cardiovascular parameters, kidney function, and renal histology were assessed after 4, 8, or 12 weeks. The 5/6 Nx group showed blood pressure elevation, cardiac hypertrophy, renal function decline, severe albuminuria, and glomerular hypertrophy. However, the glomerulosclerosis by 5/6 Nx was very mild and there was only modest tubulointerstitial inflammation and fibrosis in the 5/6 Nx group, even after 12 weeks of HPD loading. Furthermore, the sham group showed no histological changes. Thus, an HPD alone is insufficient to cause renal pathology, and a combination of 5/6 Nx and HPD loading induces mild renal pathology. Therefore, future studies of CKD using 5/6 Nx should be performed over a relatively long period of time in mice, or should be performed in other animals that are susceptible to kidney injury.