Key result
Subtotal 5/6 nephrectomy induced more severe cardiovascular and kidney consequences, including a marked increase in albuminuria (4588 vs 219 mg/g), in 129/Sv mice compared to C57BL/6JRj mice.
Why the study?
Cardiovascular consequences of 5/6 nephrectomy in mice are rarely reported in detail, and comparative data between different genetic strains are scarce.
Does the genetic background (129/Sv vs C57BL/6JRj) influence the renal, cardiac, and vascular consequences of 5/6 nephrectomy in mice?
Does the genetic background (129/Sv vs C57BL/6JRj) influence the renal, cardiac, and vascular consequences of 5/6 nephrectomy in mice?
Absolute Event Rate: 4588% vs 219%
p-value: p=<0.001
The 129/Sv mouse strain exhibits more pronounced cardiovascular and renal consequences following 5/6 nephrectomy compared to the C57BL/6JRj strain, highlighting the importance of genetic background in experimental CKD models.
Genetic background modulates nephrectomy-induced cardiorenal damage in mice; leaves optimal preclinical model selection open for human translation.
Experimental models of cardiovascular diseases largely depend on the genetic background. Subtotal 5/6 nephrectomy (5/6 Nx) is the most frequently used model of chronic kidney disease (CKD) in rodents. However, in mice, cardiovascular consequences of 5/6 Nx are rarely reported in details and comparative results between strains are scarce. The present study detailed and compared the outcomes of 5/6 Nx in the 2 main strains of mice used in cardiovascular and kidney research, 129/Sv and C57BL/6JRj. Twelve weeks after 5/6 Nx, CKD was demonstrated by a significant increase in plasma creatinine in both 129/Sv and C57BL/6JRj male mice. Polyuria and kidney histological lesions were more pronounced in 129/Sv than in C57BL/6JRj mice. Increase in albuminuria was significant in 129/Sv but not in C57BL/6JRj mice. Both strains exhibited an increase in systolic blood pressure after 8 weeks associated with decreases in cardiac systolic and diastolic function. Heart weight increased significantly only in 129/Sv mice. Endothelium-dependent mesenteric artery relaxation to acetylcholine was altered after 5/6 Nx in C57BL/6JRj mice. Marked reduction of endothelium-dependent vasodilation to increased intraluminal flow was demonstrated in both strains after 5/6 Nx. Cardiovascular and kidney consequences of 5/6 Nx were more pronounced in 129/Sv than in C57BL/6JRj mice.
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Hamzaoui et al. (2020) studied Chronic kidney disease (n=40). 5/6 nephrectomy vs. Sham operation was evaluated on Urinary albumin/creatinine ratio at 8 weeks in 129/Sv mice (mg/g) (p=<0.001). Subtotal 5/6 nephrectomy induced more severe cardiovascular and kidney consequences, including a marked increase in albuminuria (4588 vs 219 mg/g), in 129/Sv mice compared to C57BL/6JRj mice.
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