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Background: Oxidative stress and inflammation are known to play central roles in the development of diabetic nephropathy (DN). Febuxostat is a novel non-purine xanthine oxidase (XO)-specific inhibitor developed to treat hyperuricemia. In this study, we investigated whether febuxostat could ameliorate DN via renoprotective mechanisms such as alleviation of oxidative stress and anti-inflammatory actions., Methods: Male Sprague-Dawley rats were divided into three groups: a normal group, a diabetes group (DM group), and a febuxostat-treated diabetes group (DM+Fx group). We administered 5 mg/kg of febuxostat to experimental rats for 7 weeks and evaluated clinical and biochemical parameters and XO and xanthine dehydrogenase (XDH) activity in hepatic tissue. The degree of oxidative stress and extent of inflammation were evaluated from urine samples and renal tissue collected from each group., Results: Diabetic rats (DM and DM+Fx groups) had higher blood glucose and kidney weight relative to body weight than normal rats. Albuminuria was significantly reduced in febuxostat-treated diabetic rats compared with untreated diabetic rats. Quantitative analysis showed that hepatic XO and XDH activities were higher in the DM groups, but decreased after treatment with febuxostat. Urinary 8-OHdG concentrations and renal cortical nitrotyrosine also indicated reduced oxidative stress in the DM+Fx group relative to the DM group. The number of ED-1-stained cells in the glomerulus and tubule of diabetic renal tissue decreased in febuxostat-treated diabetic rats relative to that of non-treated diabetic rats. Diabetic rats also expressed higher transcript levels of inflammatory genes (E-selectin and VCAM-1), an inflammation-induced enzyme (COX-2), and inflammatory mediators (ED-1 and NF-κB) than control rats; expression of these genes was significantly reduced by treatment with febuxostat., Conclusions: Febuxostat prevents diabetic renal injury such as albuminuria. This renoprotective effect appears to be due to attenuation of the inflammatory and oxidative effects of diabetes-induced renal damage through inhibition of XO and XDH activities., (© 2014 S. Karger AG, Basel.)

Ankylosing spondylitis (AS) is a chronic inflammatory disease primarily involving the spine and sacroiliac joint and rarely the kidneys. This study aimed to define the clinical and histological features and biology of renal disease in AS. We reviewed the medical records of 681 patients diagnosed with AS from November 2008 to November 2009. Baseline characteristics and laboratory and urinalysis results were reviewed. We identified patients with proteinuria or hematuria and analyzed their risk factors. After providing informed consent, 6 patients underwent a renal biopsy to determine the cause of proteinuria or hematuria. Of the 681 enrolled patients, 547 were men and 134 were women; 81 % were HLA B27 positive, and 8 % had abnormal urinalysis findings (proteinuria, 5.9 %; hematuria, 2.8 %; both, 0.7 %). Incidences of peripheral arthritis and uveitis were 29 % and 18.6 %, respectively. Immunoglobulin (Ig)A and uric acid levels were significantly different between patients with and without proteinuria. Erythrocyte sedimentation rate (ESR), total cholesterol, creatinine, and C-reactive protein (CRP) levels were not statistically significantly different between the 2 groups nor were there any significant differences in IgA, uric acid, ESR, total cholesterol, creatinine, and CRP levels between patients with and without hematuria. Six patients who had >1 g/day proteinuria underwent a renal biopsy; 2 were diagnosed with IgA nephropathy, 1 with amyloidosis, and 3 with non-specific glomerulonephropathy. In the amyloidosis patient, severe proteinuria was the dominant feature. For patients with renal amyloidosis and other forms of glomerulonephritis who initially had normal creatinine levels, tumor necrosis factor (TNF)-alpha blocker therapy resolved proteinuria, but this was not the case for patients with initial renal insufficiency. Renal involvement is not a rare complication of AS, and prognoses differ depending on kidney pathology. Serum levels of uric acid and IgA may predict renal involvement in AS. In cases where abnormal urine sediment is identified, renal biopsy is required to determine prognosis and decide the treatment protocol. Baseline serum creatinine level is important for predicting treatment response.