A 65-year-old woman with long-standing limited scleroderma over 15 years presented in January 2004 with scleroderma renal crisis with rising blood pressure, worsening of renal function and non-ST segment acute coronary syndrome. The patient's renal function deteriorated upon receiving angiotensin-converting enzyme (ACE) inhibitors, prompting coronary and renal angiography, which revealed bilateral coronary and renal artery stenosis. In scleroderma patients with renal crisis and showing deterioration of renal function, the possibility of renal artery stenosis should be excluded because ACE inhibitors in this situation carry risks for deterioration of kidney function.
Renal artery stenosis (RAS) may lead to renal injury, partly mediated through increased oxidative stress. However, the potential effects of chronic oral antioxidant intervention on the stenotic kidney remain unknown.
This study was designed to test the hypothesis that chronic antioxidant vitamin supplementation in RAS would preserve renal function and structure. Single-kidney hemodynamics and function were quantified in vivo in pigs using electron-beam CT after 12 weeks of unilateral RAS (n=7), a similar degree of RAS orally supplemented with vitamins C (1 g) and E (100 IU/kg) (RAS+Vitamins, n=7), or controls (normal, n=7).
Renal tissue was studied ex vivo using Western blotting and immunohistochemistry. Mean arterial pressure was similarly elevated in both RAS groups, while ischemic renal volume and glomerular filtration rate were similarly reduced.
Renal blood flow was decreased in RAS compared with normal (326.5±99.9 versus 553.4±48.7 mL/min, respectively, P=0.01), but preserved in RAS+Vitamins (485.2±104.1 mL/min, P=0.3 versus normal). The marked increase in the expression of the NADPH-oxidase subunits p47phox and p67phox, nitrotyrosine, endothelial and inducible nitric oxide synthase, and nuclear factor-B observed in RAS (P<0.05 versus normal) was normalized in RAS+Vitamins (P>0.1).
Furthermore, trichrome staining and the expression of transforming growth factor-ß and tissue inhibitor of matrix-metalloproteinase-1 were also decreased in RAS+Vitamins.
In conclusion, chronic blockade of the oxidative stress pathway in RAS using antioxidant vitamins improved renal hemodynamics and decreased oxidative stress, inflammation, and fibrosis in the ischemic kidney. These observations underscore the involvement of oxidative stress in renal injury in RAS and support a role for antioxidant vitamins in preserving the ischemic kidney.