NEJM：一种治疗常染色体显性多囊肾病的潜在疗法

2012年11月6日来自梅奥诊所的研究者通过研究发现，一种新型的药物疗法在治疗常染色体显性多囊肾病（ADPKD）上表现出较好的作用，这种药物名为托伐普坦，在长达三年的研究中，其可以有效减缓肾脏包囊的生长速度。相关研究刊登于国际杂志NEJM上。

通过多中心的研究表明，药物托伐普坦相比安慰剂，在治疗期间可以明显降低ADPKD患者肾脏包囊尺寸将近50%。

研究者Vicente Torres博士说，常染色体显性多囊肾病是常见的遗传性疾病，也是全球常见的第四大引发肾衰竭的病因。

在很多该疾病的患者中，肾脏中包囊的生长会破坏正常组织、引发高血压以及疼痛并发症，严重影响患者的生活质量。该项研究揭示了该疾病的一种潜在的疗法，可以减少患者的症状，并且减缓患者肾脏功能的降低速度。

研究者表示，尽管此项研究发现很鼓舞人心，可是药物托伐普坦并不被批准进行应用，相关研究由大冢制药株式会社提供支持。

与肾病相关的拓展阅读： 

• JASN：揭示治疗糖尿病肾病的新型靶点
• Kidney Inter：慢性肾病或可改变机体肠道菌群
• Diabetes Care：低水平高密度脂蛋白胆固醇升高糖尿病肾病风险
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• JACC:贝特类药物可降低慢性肾病患者心血管事件发生的风险 更多信息请点击：有关肾病更多资讯

Tolvaptan in Patients with Autosomal Dominant Polycystic Kidney Disease

Background The course of autosomal dominant polycystic kidney disease (ADPKD) is often associated with pain, hypertension, and kidney failure. Preclinical studies indicated that vasopressin V2-receptor antagonists inhibit cyst growth and slow the decline of kidney function. Full Text of Background... Methods In this phase 3, multicenter, double-blind, placebo-controlled, 3-year trial, we randomly assigned 1445 patients, 18 to 50 years of age, who had ADPKD with a total kidney volume of 750 ml or more and an estimated creatinine clearance of 60 ml per minute or more, in a 2:1 ratio to receive tolvaptan, a V2-receptor antagonist, at the highest of three twice-daily dose regimens that the patient found tolerable, or placebo. The primary outcome was the annual rate of change in the total kidney volume. Sequential secondary end points included a composite of time to clinical progression (defined as worsening kidney function, kidney pain, hypertension, and albuminuria) and rate of kidney-function decline. Full Text of Methods... Results Over a 3-year period, the increase in total kidney volume in the tolvaptan group was 2.8% per year (95% confidence interval [CI], 2.5 to 3.1), versus 5.5% per year in the placebo group (95% CI, 5.1 to 6.0; P<0.001). The composite end point favored tolvaptan over placebo (44 vs. 50 events per 100 follow-up-years, P=0.01), with lower rates of worsening kidney function (2 vs. 5 events per 100 person-years of follow-up, P<0.001) and kidney pain (5 vs. 7 events per 100 person-years of follow-up, P=0.007). Tolvaptan was associated with a slower decline in kidney function (reciprocal of the serum creatinine level, −2.61 [mg per milliliter]−1 per year vs. −3.81 [mg per milliliter]−1 per year; P<0.001). There were fewer ADPKD-related adverse events in the tolvaptan group but more events related to aquaresis (excretion of electrolyte-free water) and hepatic adverse events unrelated to ADPKD, contributing to a higher discontinuation rate (23%, vs. 14% in the placebo group). Full Text of Results... Conclusions Tolvaptan, as compared with placebo, slowed the increase in total kidney volume and the decline in kidney function over a 3-year period in patients with ADPKD but was associated with a higher discontinuation rate, owing to adverse events. (Funded by Otsuka Pharmaceuticals and Otsuka Pharmaceutical Development and Commercialization; TEMPO 3:4 ClinicalTrials.gov number, NCT00428948.)