From the Division of Renal Diseases and Hypertension University of Colorado, Aurora (R.J.J.).
Department of Medicine, Massachusetts General Hospital, Boston (H.K.C.).
Hypertension. 2019 Jul;74(1):95-101. doi: 10.1161/HYPERTENSIONAHA.119.12727. Epub 2019 May 13.
Serum urate is correlated with blood pressure (BP), and lowering urate may decrease BP, but a consistent effect has not been observed. Here, we evaluated whether pegloticase, a recombinant uricase conjugated to polyethylene glycol, which can lead to persistently low serum urate levels (<1 mg/dL), can modulate BP in subjects with chronic refractory gout. This post hoc analysis used results from two 6-month randomized clinical trials in which subjects were treated with 8 mg pegloticase every 2 or 4 weeks (q2w or q4w) or placebo. Responders in this study were defined as those individuals in whom a persistently low urate level (<6 mg/dL and usually <1 mg/dL) was maintained. Serial sitting BP was measured in 173 subjects, and estimated glomerular filtration rate was determined at baseline and after 3 and 6 months. Significant reductions in mean arterial pressure (MAP) from baseline to 6 months were noted in q2w responders ( P=0.0028), whereas reductions in MAP in other groups were not significant. Significant decreases in both systolic and diastolic BP paralleled the change in MAP. Of the 62% of q2w responders exhibiting persistent decreases in MAP, there were no significant differences in baseline age, sex, race, weight, body mass index, history of hypertension, hyperlipidemia, history of coronary artery disease, gout duration, MAP, serum urate, estimated glomerular filtration rate or urinary uric acid/creatinine ratio compared with those who did not lower MAP. No significant changes in estimated glomerular filtration rate occurred in any of the groups during the study. Responders to biweekly pegloticase who maintained a persistently lower serum urate level throughout the trial experienced significant reductions in both systolic and diastolic BP that were independent of changes in renal function. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT00325195.
尿酸与血压（BP）相关，降低尿酸可能会降低血压，但尚未观察到一致的效果。在这里，我们评估了聚乙二醇尿酸酶（一种与聚乙二醇偶联的重组尿酸酶，可以导致持续的低血清尿酸水平（<1mg/dL））是否可以调节慢性难治性痛风患者的血压。本事后分析使用了两项 6 个月随机临床试验的结果，这些试验中，患者接受了 8mg 聚乙二醇尿酸酶每 2 或 4 周（q2w 或 q4w）或安慰剂治疗。本研究中的应答者定义为持续保持低尿酸水平（<6mg/dL，通常<1mg/dL）的个体。173 名受试者进行了连续坐位血压测量，并在基线及 3 个月和 6 个月时测定肾小球滤过率。q2w 应答者从基线到 6 个月时平均动脉压（MAP）显著降低（P=0.0028），而其他组的 MAP 降低不显著。收缩压和舒张压均显著降低，与 MAP 变化平行。在 62%的 q2w 应答者中，持续降低 MAP 的患者与未降低 MAP 的患者相比，基线年龄、性别、种族、体重、体重指数、高血压病史、高脂血症病史、冠心病病史、痛风持续时间、MAP、血清尿酸、肾小球滤过率或尿尿酸/肌酐比值均无显著差异。在研究期间，任何组的肾小球滤过率均无显著变化。在整个试验中持续保持低血清尿酸水平的 q2w 应答者，其收缩压和舒张压均显著降低，且与肾功能变化无关。临床试验注册- URL：http://www.clinicaltrials.gov 。独特标识符：NCT00325195。
