Effects of 5/6 nephrectomy on renal function and blood pressure in mice

Abstract

Background/aims: The rat has been the most used experimental animal for studies of cardiovascular and kidney diseases. However, it is notable that there is increasing importance placed on the use of the mouse model to increase understanding of these pathophysiologies. The aim of the present study was to induce chronic kidney disease in a mouse model and to evaluate the resulting changes in blood pressure (BP) and in renal morphology and function.

Methods: Adult male C57BL/6 mice underwent 5/6 nephrectomy (5/6 Nx) or a sham operation (Sham). Two weeks later, conscious animals were subjected to a 24-hour urine collection and to a direct measurement of BP.

Results: Compared to Sham animals, 5/6 Nx mice showed reduced creatinine clearance (3-fold, p<0.01), proteinuria (1.5-fold, p<0.01) and uremia (4-fold, p<0.01), as well as high blood pressure (~20%, p<0.01). 5/6 Nx animals showed increases in the 24 h urine excretion of Na(+) (2-fold, p<005), K(+) (~2-fold, <0.01) and Ca(2+) (~12-fold). Kidney histology of 5/6 Nx mice also demonstrated glomerular hypertrophy (1.5-fold, p<0.05), mesangial expansion (~40%, p<0.01) and increased glomerular collagen deposition (~30%, p<0.05).

Conclusion: Induction of 5/6 nephrectomy in mice for two weeks leads to systemic arterial hypertension and to functional and morphological damage of the remnant kidney, which are considered the main characteristics of chronic kidney disease.

Keywords: 5/6 nephrectomy; Chronic kidney disease; mice; renal function.

Figure 1

Creatinine clearance, uremia and proteinuria levels. 5/6 nephrectomized (5/6 Nx) animals presented reduced glomerular filtration rate, as indicated by reduced creatinine clearance, increased uremia and glomerular damage demonstrated by the increase in proteinuria levels compared to Sham animals. Values are means ± SEM (n= 8 to 10 per group), **p<0.01 vs. Sham group.

Figure 2

Hemodynamic measurements. Direct measurements of systolic, diastolic and mean arterial blood pressure and heart rate show a marked arterial hypertension two weeks after 5/6 nephrectomy (5/6 Nx) compared to Sham animals. Values are means ± SEM (n= 6 to 8 per group), **p<0.01 vs. Sham group.

Figure 3

Renal Histological Analysis. Bar graphs and respective representative pictures show hypertrophy of remnant glomeruli, mesangial expansion and increased collagen deposition in 5/6 Nx animals compared to Sham animals. Values are the means ± SEM (n= 6 to 8 per group), **p<0.01 vs. Sham group. Scale bar: 10 μm.