Background
Topiroxostat, a selective xanthine oxidase inhibitor, shows effective reduction in the serum urate level in hyperuricemic patients with or without gout. The objective of this study was to evaluate the efficacy and safety of topiroxostat in hyperuricemic stage 3 chronic kidney disease patients with or without gout.MethodsThe study design was a 22-week, randomized, multicenter, double-blind study. The enrolled patients were randomly assigned to treatment with topiroxostat 160 mg/day (n = 62) or to the placebo (n = 61). The endpoints were the percent change in the serum urate level, change in the estimated glomerular filtration rate, the urinary albumin-to-creatinine ratio, the proportion of patients with serum urate levels of 356.88 μmol/L or less, blood pressure, and serum adiponectin.ResultsAfter 22 weeks, although the changes in the estimated glomerular filtration rate and blood pressure were not significant, the percent change in the serum urate level (−45.38 vs. −0.08 %, P < 0.0001) and the percent change in urinary albumin-to-creatinine ratio (−33.0 vs. −6.0 %, P = 0.0092) were found to have decreased in the topiroxostat as compared with the placebo. Although the incidence of ‘alanine aminotransferase increased’ was higher in the topiroxostat, serious adverse event rates were similar in the two groups.ConclusionTopiroxostat 160 mg effectively reduced the serum urate level in the hyperuricemic stage 3 chronic kidney disease patients with or without gout.
ObjectiveA genome-wide association study (GWAS) of gout and its subtypes was performed to identify novel gout loci, including those that are subtype-specific.MethodsPutative causal association signals from a GWAS of 945 clinically defined gout cases and 1213 controls from Japanese males were replicated with 1396 cases and 1268 controls using a custom chip of 1961 single nucleotide polymorphisms (SNPs). We also first conducted GWASs of gout subtypes. Replication with Caucasian and New Zealand Polynesian samples was done to further validate the loci identified in this study.ResultsIn addition to the five loci we reported previously, further susceptibility loci were identified at a genome-wide significance level (p<5.0×10−8): urate transporter genes (SLC22A12 and SLC17A1) and HIST1H2BF-HIST1H4E for all gout cases, and NIPAL1 and FAM35A for the renal underexcretion gout subtype. While NIPAL1 encodes a magnesium transporter, functional analysis did not detect urate transport via NIPAL1, suggesting an indirect association with urate handling. Localisation analysis in the human kidney revealed expression of NIPAL1 and FAM35A mainly in the distal tubules, which suggests the involvement of the distal nephron in urate handling in humans. Clinically ascertained male patients with gout and controls of Caucasian and Polynesian ancestries were also genotyped, and FAM35A was associated with gout in all cases. A meta-analysis of the three populations revealed FAM35A to be associated with gout at a genome-wide level of significance (pmeta=3.58×10−8).ConclusionsOur findings including novel gout risk loci provide further understanding of the molecular pathogenesis of gout and lead to a novel concept for the therapeutic target of gout/hyperuricaemia.
ObjectiveGrowing qualitative evidence reveals that many patients with chronic illnesses struggle to rebuild a positive self-image after diagnosis while attempting to find a balance between their current physical status and their ongoing social duties. One factor destabilizing patients’ identities is self-stigma, which seems to affect their behavioral goals through decreased self-efficacy. We hypothesized that self-stigma would be an independent factor, distinct from self-efficacy, for developing self-care behaviors in patients with type 2 diabetes.MethodsWe used a consecutive sample of 209 outpatients with type 2 diabetes treated by endocrinologists at two university hospitals, one general hospital and one clinic. We performed multiple linear regression analyses to test the relationship between the patients’ activation levels for self-care behaviors (dependent variable) and self-stigma, self-efficacy, and depression symptoms (independent variables), adjusting for covariates involving sociodemographic and clinical characteristics.ResultsIn a multiple linear regression model adjusted for prior covariates, there was significant association between self-stigma and activation levels for self-care behaviors in patients with type 2 diabetes (adjusted R2=0.26, F (12,196)=7.20, p<0.001). The standardized partial regression coefficient of self-stigma was −0.23 (p=0.001), whereas that of self-efficacy was 0.19 (p=0.007).ConclusionsSelf-stigma is a negative independent factor, separate from self-efficacy, affecting the self-care behaviors of patients with type 2 diabetes. Self-stigma also has, at least, a similar impact on self-care behaviors to that of self-efficacy. To optimize treatment outcomes, patients’ self-stigma should be minimized, whereas their self-efficacy should be enhanced.
ObjectivesTo determine whether febuxostat with stepwise dose increase is as useful as colchicine prophylaxis in reducing gout flares during the initial introduction of urate-lowering therapy in patients with gout in comparison with febuxostat with no dose titration.MethodsIn this prospective, multicentre, randomised open-label comparative study, patients were randomised to group A (stepwise dose increase of febuxostat from 10 to 40 mg/day), group B (fixed-dose febuxostat 40 mg/day plus colchicine 0.5 mg/day) or group C (fixed-dose febuxostat 40 mg/day) and observed for 12 weeks. Gout flare was defined as non-steroidal anti-inflammatory drug use for gout symptoms.ResultsA total of 255 patients were randomised, and 241 patients were treated. Among the treated patients, gout flares were experienced by 20/96 (20.8%) in group A, 18/95 (18.9%) in group B and 18/50 (36.0%) in group C. The incidence of flare was significantly lower in groups A and B than that in group C (P=0.047 and P=0.024, respectively), although the differences were not significant after correction for multiple comparisons. No significant difference was noted between the incidence of gout flare in groups A and B.ConclusionsOur data suggested that stepwise dose increase of febuxostat and low-dose colchicine prophylaxis effectively reduced gout flares in comparison with fixed-dose febuxostat alone. Stepwise dose increase of febuxostat may be an effective alternative to low-dose colchicine prophylaxis during the introduction of urate-lowering therapy.Trial registration numberUMIN 000008414.
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