Abstract：
In observational studies, serum urate positively associates with cardiometabolic and kidney diseases. We analyzed data from a randomised placebo-controlled trial to determine whether moderate hyperuricemia induced by inosine affects cardiometabolic and kidney function markers. One hundred and twenty post-menopausal women were recruited into a 6-month randomised, double-blind, placebo-controlled trial of inosine for bone health. Change from baseline in the following pre-specified endpoints was analyzed: body mass index; blood pressure; lipid profile; C-reactive protein; fasting glucose; insulin; HbA1c; serum creatinine; and estimated glomerular filtration rate (eGFR). Despite increases in serum urate levels (+ 0.17 mmol/L at week 6, P < 0.0001), no significant between-group differences were observed in cardiometabolic markers, with the exception of lower fasting glucose concentrations with inosine at week 19. In the inosine group, change in serum urate correlated with change in serum creatinine (r = 0.41, P = 0.0012). However, there was no between-group difference in serum creatinine values. Over the entire study period, there was no significant difference in eGFR (ANCOVA P = 0.13). Reduction in eGFR was greater in the inosine group at Week 13 (mean difference - 4.6 mL/min/1.73 m2, false detection rate P = 0.025), with no between-group difference in eGFR at other time points. These data indicate that increased serum urate does not negatively influence body mass index, blood pressure, lipid profile, or glycaemic control. Serum urate changes associated with inosine intake correlate with changes in serum creatinine, but this does not lead to clinically important reduction in kidney function over 6 months.Clinical trial registration number: Australia and New Zealand Clinical Trials Registry (ACTRN12617000940370), registered 30/06/2017.
摘要：
在观察性研究中,血清尿酸与心脏代谢和肾脏疾病呈正相关。我们分析了一项随机安慰剂对照试验的数据，以确定肌苷诱导的中度高尿酸血症是否会影响心脏代谢和肾功能标志物。招募了120名绝经后妇女，进行了为期6个月的随机分组，双盲,肌苷对骨骼健康的安慰剂对照试验。分析了以下预先指定的终点相对于基线的变化：体重指数;血压;血脂;C反应蛋白;空腹血糖;胰岛素;HbA1c;血清肌酐;和估计的肾小球滤过率（eGFR）。尽管血清尿酸水平增加（第6周时+0.17mmol/L，P<0.0001），在心脏代谢标志物中没有观察到显著的组间差异,除了在第19周使用肌苷的空腹血糖浓度较低。在肌苷组中,血清尿酸的变化与血清肌酐的变化相关(r=0.41,P=0.0012)。然而,血清肌酐值无组间差异.在整个研究期间,eGFR无显著差异(ANCOVAP=0.13)。在第13周，肌苷组的eGFR降低更大（平均差异-4.6mL/min/1.73m2，误检率P=0.025），其他时间点的eGFR无组间差异。这些数据表明，血清尿酸升高不会对体重指数产生负面影响，血压,血脂谱,或血糖控制。与肌苷摄入相关的血清尿酸变化与血清肌酐变化相关，但这不会导致6个月后肾功能的临床重要降低。临床试验登记号：澳大利亚和新西兰临床试验注册中心（ACTRN12617000940370），注册30/06/2017。
