Bartáková Vendula, Kuricová Katarína, Pácal Lukáš, Nová Zuzana, Dvořáková Veronika, Švrčková Martina, Malúšková Denisa, Svobodová Ivana, Řehořová Jitka, Svojanovský Jan, Olšovský Jindřich, Bělobrádková Jana, Kaňková Kateřina
Department of Pathophysiology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic.
Department of Pathophysiology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic.
J Diabetes Complications. 2016 Sep-Oct;30(7):1300-7. doi: 10.1016/j.jdiacomp.2016.06.002. Epub 2016 Jun 7.
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.
Study comprised 422 subjects with diabetes duration at least 15years 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≥420μmol/l for men and ≥360μmol/l for women and/or allopurinol treatment). Five SNPs in the SLC2A9 and ABCG2 genes were determined by PCR.
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 49months compared with remaining subjects (32months, 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 ≤377.5μmol/l for men and ≤309.0μmol/l for women. We found no differences in allele or genotype frequencies in selected SNPs between patients with and without hyperuricemia (all P>0.05).
Our study demonstrated that initial hyperuricemia or need for allopurinol is an independent risk factor for DKD progression and that SUA levels in diabetic subjects conferring protection against DKD progression might be lower than current cut-offs for general population.
本研究的目的是：（i）在一组2型糖尿病（T2DM）患者中确定血清尿酸（SUA）对糖尿病肾病（DKD）进展和主要不良心血管事件（MACE）的预后价值；（ii）确定别嘌醇治疗的最终保护作用；（iii）确定尿酸转运蛋白基因变异性对DKD进展的影响；（iv）确定DKD患者中SUA的最佳临界值。
研究纳入422名糖尿病病程至少15年的受试者，中位随访时间为43[四分位间距22 - 77]个月。根据蛋白尿或慢性肾脏病（CKD）分期的变化，将参与者分为病情稳定或进展者。基线时，68%的患者有高尿酸血症（男性SUA≥420μmol/l，女性≥360μmol/l和/或接受别嘌醇治疗）。通过聚合酶链反应（PCR）测定SLC2A9和ABCG2基因中的5个单核苷酸多态性（SNP）。
根据初始高尿酸血症的有无定义亚组进行的事件发生时间分析显示，在所有三个终点均存在显著差异（DKD进展P<0.0001，MACE为P = 0.0022，死亡为P = 0.0002，对数秩检验）。SUA正常且不需要别嘌醇的受试者DKD进展的中位时间为49个月，而其余受试者为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/或别嘌醇治疗）是DKD进展的独立预测因素，与基线CKD分期无关。通过ROC分析确定的T2DM受试者的最佳临界值为男性≤377.5μmol/l，女性≤309.0μmol/l。我们发现高尿酸血症患者与非高尿酸血症患者所选SNP的等位基因或基因型频率无差异（所有P>0.05）。
我们的研究表明，初始高尿酸血症或需要别嘌醇是DKD进展的独立危险因素，并且糖尿病患者中对DKD进展具有保护作用的SUA水平可能低于目前针对一般人群的临界值。
