Compared With Radical Nephrectomy, Nephron-sparing Partial Nephrectomy Protects Apolipoprotein E-deficient Mice From Atherosclerosis Progression

Urology. 2015 May;85(5):1215.e9-1215.e15. doi: 10.1016/j.urology.2015.02.004.

Abstract

Objective: To compare the effect of radical with partial unilateral nephrectomy on the development of atherosclerosis in the apolipoprotein E (apoE(-/-))-deficient mouse model.

Methods: Male apoE(-/-) mice were randomly assigned to the following 3 groups: (1) radical left nephrectomy (RNX, 15 mice), (2) partial left nephrectomy (PNX, 15 mice), and (3) left kidney sham operation (sham-op, 12 mice). The right kidney was left intact in all groups. At 16 weeks after surgery, mice were killed, and atherosclerotic surface area and plaque composition were evaluated in the aortic root and the descending aorta using a quantitative morphologic image processing method.

Results: At killing, RNX mice had significantly higher serum urea, total cholesterol, and triglyceride concentrations than PNX and sham-op groups (P <.05, P <.001, and P <.0001, respectively). Atherosclerotic lesions in the aortic root and the descending aorta were significantly increased in the RNX mice compared with those in the PNX and sham-op mice (P <.05 and P <.001, respectively). In addition, aortic plaques of RNX mice showed a significant increase in nitrotyrosine expression (P <.02) and collagen content (P <.05), whereas the degree of macrophage infiltration was comparable between the groups.

Conclusion: We show for the first time that PNX, as compared with RNX, slows the progression of vascular disease in a mouse model of severe atherosclerosis. This effect was mediated by the prevention of chronic kidney disease-induced increases in oxidative stress and lipid disturbances. Our finding can be interpreted as being in support of an expanded use of nephron-sparing techniques in atherosclerosis-prone patients who need to undergo kidney cancer surgery.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins E / deficiency*
  • Atherosclerosis / etiology
  • Atherosclerosis / prevention & control*
  • Disease Progression
  • Mice
  • Nephrectomy / methods*
  • Nephrons
  • Organ Sparing Treatments

Substances

  • Apolipoproteins E