Hyperuricemia contributes to the faster progression of diabetic kidney disease in type 2 diabetes mellitus
Hyperuricemia contributes to the faster progression of diabetic kidney disease in type 2 diabetes mellitus
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DOI：
10.1016/j.jdiacomp.2016.06.002
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发表时间：
2016-09-01
影响因子：
3
通讯作者：
Kankova, Katerina
中科院分区：
文献类型：
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作者：
Bartakova, Vendula;Kuricova, Katarina;Kankova, Katerina
目的：本研究的目的是 (i) 确定血清尿酸 (SUA) 对 T2DM 患者队列中糖尿病肾病 (DKD) 进展和主要不良心血管事件 (MACE) 的预后价值，(ii) 确定别嘌呤醇治疗的最终保护作用，(iii) 确定 UA 转运蛋白的遗传变异对 DKD 进展的影响，以及 (iv) 确定 DKD 患者 SUA 的最佳临界值。方法：研究包括 422 名糖尿病病程至少 15 年的受试者，随访中位数为 43 [IQR 22-77] 个月。根据参与者蛋白尿或慢性肾脏病（CKD）阶段的变化，将其分为稳定期或进展期。基线时，68% 的患者患有高尿酸血症（男性 SUA >= 420 mu mol/l，女性 >= 360 mu mol/l 和/或别嘌呤醇治疗）。通过 PCR 测定了 SLC2A9 和 ABCG2 基因中的 5 个 SNP。 结果：对根据是否存在初始高尿酸血症定义的亚组进行的事件发生时间分析显示，所有三个终点均存在显着差异（DKD 进展 P < 0.0001，MACE P = 0.0022，死亡 P = 0.0002，对数秩检验）。与其余受试者相比，不需要别嘌呤醇的 SUA 正常受试者的 DKD 进展中位时间为 49 个月（32 个月，P = 0.0002，对数秩检验）。多变量 Cox 回归模型显示，高尿酸血症（即高 SUA 和/或别嘌呤醇治疗）是 DKD 进展的重要预测因子，与基线 CKD 分期无关。通过 ROC 分析确定的 T2DM 受试者的最佳截止值是
Aims: The aims of the study were (i) to ascertain prognostic value of serum uric acid (SUA) for diabetic kidney disease (DKD) progression and major adverse cardiovascular event (MACE) in a cohort of T2DM patients, (ii) to ascertain eventual protective effect of allopurinol treatment, (iii) to determine the effect of genetic variability in UA transporters on DKD progression, and (iv) to define optimal cut-off values for SUA in patients with DKD.Methods: Study comprised 422 subjects with diabetes duration at least 15 years followed-up for a median of 43 [IQR 22-77] months. Participants were categorized into stable or progressors according to their change in albuminuria or chronic kidney disease (CKD) stage. At baseline, 68% patients had hyperuricemia (SUA >= 420 mu mol/l for men and >= 360 mu mol/l for women and/or allopurinol treatment). Five SNPs in the SLC2A9 and ABCG2 genes were determined by PCR.Results: Time-to-event analysis with subgroups defined by the presence/absence of initial hyperuricemia revealed significant differences in all three end-points (P < 0.0001 for DKD progression, P = 0.0022 for MACE and P = 0.0002 for death, log-rank test). Subjects with normal SUA not requiring allopurinol had median time to DKD progression 49 months compared with remaining subjects (32 months, P = 0.0002, log-rank test). Multivariate Cox regression model revealed hyperuricemia (i.e. high SUA and/or allopurinol treatment) significant predictor of DKD progression independent of baseline CKD stage. Optimal cut-off values identified by ROC analysis for T2DM subjects were