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Subtotal (5/6) nephrectomy 

For 5/6 nephrectomy, animals are anesthetized, and under aseptic conditions, subtotal renal ablation of the left kidney is produced by amputation of both renal poles. One week later the mice are subjected to a right nephrectomy via a dorsal lumbotomy incision (5) (6). 129/Sv mice develop more significant glomerulosclerosis, proteinuria, increases in blood pressure and apparent renal failure than do C57BL/6 mice after 5/6 nephrectomy (6).

Subtotal nephrectomy > Literature Section

Publications for Subtotal nephrectomy (2)

Cheng H, Zhang M, Moeckel GW, Zhao Y, Wang S, Qi Z, Breyer MD, Harris RC. Expression of mediators of renal injury in the remnant kidney of ROP mice is attenuated by cyclooxygenase-2 inhibition. Nephron Exp Nephrol (2005) 101:e75-85
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To investigate the effects of cyclooxygenase-2 (COX-2) inhibition on renal injury of mice, ROP mice were subjected to subtotal ablation ('remnant'). A subset of the remnant group was treated with a selective COX-2 inhibitor, SC58236, in the drinking water. At 12 weeks the remnant group developed significant albuminuria (181.3 +/15.8 microg/24 h), which was blunted by SC58236 treatment (138.9 +/- 17.1; p < 0.05 compared to remnant). SC58236 did not alter systemic blood pressure or GFR significantly. Immunoreactive COX-2 was upregulated in remnant (1.88 +/0.35 fold sham, n = 8, p < 0.05), which was blunted by SC58236 (to 1.26 +/0.31 fold sham). Collagen IV mRNA increased significantly in remnant kidneys (2.69 +/0.34 fold sham, n = 8, p < 0.05), and this increase was inhibited by SC58236 treatment (to 1.84 +/0.32 fold control). Immunoreactive TGF-beta1, connective tissue growth factor, HGF receptor, c-Met, and fibronectin all increased in remnant (2.85 +/0.51, 3.83 +/0.55, 2.56 +/0.31, and 2.80 +/- 0.39 fold sham respectively, n = 4-8, p < 0.05), and SC58236 blunted the increases (to 1.45 +/0.34, 1.85 +/0.13, 1.75 +/0.30, and 1.60 +/0.32 fold sham). Immunohistochemistry indicated that the major localization for these progression factors was in the tubulointerstitium, especially in the scar area, which is in agreement with the expression of a macrophage marker, F4/80. Therefore, these results indicate that in a mouse model of subtotal renal ablation, COX-2 inhibition blocks expression of mediators of renal tubulointerstitial injury. CI Copyright 2005 S. Karger AG, Basel.

Ma LJ, Fogo AB. Model of robust induction of glomerulosclerosis in mice: importance of genetic background. Kidney Int (2003) 64:350-5
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BACKGROUND: Increasing evidence suggests that genetic background plays an important role in the development of progressive glomerulosclerosis. The remnant kidney model (RKM) of progressive renal disease has been used extensively in rats. However, C57BL/6 mice are resistant to glomerulosclerosis with RKM induced by either pole amputation or renal artery ligation. A pole resection protocol, applied in 129/Sv mice, induced only mild glomerulosclerosis. We present here a highly reproducible, modified RKM approach to successfully establish a glomerulosclerosis model in mice. METHODS: Male C57BL/6 (N = 17), 129/Sv (N = 20) and Swiss-Webster (N = 3) mice underwent RKM as follows: the lower branch of the left renal artery was ligated to produce about one third infarct; the upper pole of the left kidney (about one third kidney size) was removed by cautery and the right kidney was nephrectomized to induce a total 5/6 nephrectomy (Nx). In some C57BL/6 mice, 7/8 nephrectomy was induced by removing additional renal mass from the upper pole of the left kidney by cautery. Systolic blood pressure (BP) was measured in conscious mice using a tail-cuff blood pressure monitor and animals were sacrificed at 9, 12, 18, and 24 weeks after nephrectomy. Kidneys were harvested for morphologic analysis. RESULTS: BP in C57BL/6 mice increased slightly after 5/6 nephrectomy over time without significant difference compared to baseline blood pressure except at 8 weeks (blood pressure at week 0, 98 +/1 mm Hg; week 4, 105 +/2 mm Hg; week 8, 113 +/4 mm Hg; and week 12, 110 +/3 mm Hg). Blood presssure remained normal in C57BL/6 mice at 18 weeks after 7/8 nephrectomy (103 +/2 mm Hg). Blood pressure in 129/Sv mice increased significantly after 5/6 nephrectomy from 4 to 12 weeks (week 0, 112 +/3 mm Hg; week 4, 161 +/9 mm Hg; week 8, 166 +/5 mm Hg; and week 12, 176 +/5 mm Hg; P < 0.01 weeks 4, 8, and 12 vs. week 0 blood pressure). Urine protein excretion in C57BL/6 mice increased only at 4 weeks after 5/6 nephrectomy, and was back to normal at 8 and 12 weeks (week 0, 13.2 +/1.4 mg/24 hours; week 4, 20.5 +/1.8 mg/24 hours; week 8, 18.8 +/1.6 mg/24 hours; and week 12, 17.2 +/1.2 mg/24 hours, P < 0.05 week 4 vs. week 0). 129/Sv mice developed significant proteinuria 12 weeks after 5/6 nephrectomy compared to their baseline and to levels achieved in C57BL/6 mice (week 0, 17.2 +/1 mg/24 hours; week 4, 14.9 +/1.8 mg/24 hours; week 8, 23.8 +/6.7 mg/24 hours; and week 12, 36.3 +/6.6 mg/24 hours, P < 0.01 week 12 vs. week 0; P < 0.01 129/Sv vs. C57BL/6 at week 12). Mortality varied in response to nephrectomy injury in the different strains. Ten percent of C57BL/6 and 43% of 129/Sv died within 12 weeks after 5/6 nephrectomy. Although 50% of C57BL/6 mice died by 12 weeks after 7/8 nephrectomy, there was only mild glomerulosclerosis (<5%) in C57BL/6 mice even at 24 weeks after 5/6 nephrectomy or 18 weeks after 7/8 nephrectomy. In contrast, glomerulosclerosis was marked in both 129/Sv mice and Swiss-Webster mice as early as 9 weeks after 5/6 nephrectomy: 42% of glomeruli showed sclerosis in 129/Sv mice [average sclerosis index (SI), 0 to 4+ scale, 1.08] vs. 24% in Swiss-Webster mice (average SI, 0.57). Tubulointerstitial fibrosis developed in parallel with glomerulosclerosis in both 129/Sv and Swiss-Webster mice. CONCLUSION: We conclude that genetic background is one of the important factors determining the susceptibility to the development of glomerulosclerosis in mice. We speculate that the superior effects of renal artery ligation plus cautery to produce glomerulosclerosis may result from higher blood pressure responses due to local ischemia activating the renin-angiotensin system.

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Last updated on 2013-11-06 Moderated by Raymond Harris