摘要

BACKGROUND:Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent genetically determined renal disease. In affected patients, renal function may progressively decline up to end-stage renal disease (ESRD), and approximately 10% of those with ESRD are affected by ADPKD. The somatostatin analog octreotide long-acting release (octreotide-LAR) slows renal function deterioration in patients in early stages of the disease. We evaluated the renoprotective effect of octreotide-LAR in ADPKD patients at high risk of ESRD because of later-stage ADPKD. METHODS AND FINDINGS:We did an internally funded, parallel-group, double-blind, placebo-controlled phase III trial to assess octreotide-LAR in adults with ADPKD with glomerular filtration rate (GFR) 15-40 ml/min/1.73 m2. Participants were randomized to receive 2 intramuscular injections of 20 mg octreotide-LAR (n = 51) or 0.9% sodium chloride solution (placebo; n = 49) every 28 days for 3 years. Central randomization was 1:1 using a computerized list stratified by center and presence or absence of diabetes or proteinuria. Co-primary short- and long-term outcomes were 1-year total kidney volume (TKV) (computed tomography scan) growth and 3-year GFR (iohexol plasma clearance) decline. Analyses were by modified intention-to-treat. Patients were recruited from 4 Italian nephrology units between October 11, 2011, and March 20, 2014, and followed up to April 14, 2017. Baseline characteristics were similar between groups. Compared to placebo, octreotide-LAR reduced median (95% CI) TKV growth from baseline by 96.8 (10.8 to 182.7) ml at 1 year (p = 0.027) and 422.6 (150.3 to 695.0) ml at 3 years (p = 0.002). Reduction in the median (95% CI) rate of GFR decline (0.56 [-0.63 to 1.75] ml/min/1.73 m2 per year) was not significant (p = 0.295). TKV analyses were adjusted for age, sex, and baseline TKV. Over a median (IQR) 36 (24 to 37) months of follow-up, 9 patients on octreotide-LAR and 21 patients on placebo progressed to a doubling of serum creatinine or ESRD (composite endpoint) (hazard ratio [HR] [95% CI] adjusted for age, sex, baseline serum creatinine, and baseline TKV: 0.307 [0.127 to 0.742], p = 0.009). One composite endpoint was prevented for every 4 treated patients. Among 63 patients with chronic kidney disease (CKD) stage 4, 3 on octreotide-LAR and 8 on placebo progressed to ESRD (adjusted HR [95% CI]: 0.121 [0.017 to 0.866], p = 0.036). Three patients on placebo had a serious renal cyst rupture/infection and 1 patient had a serious urinary tract infection/obstruction, versus 1 patient on octreotide-LAR with a serious renal cyst infection. The main study limitation was the small sample size. CONCLUSIONS:In this study we observed that in later-stage ADPKD, octreotide-LAR slowed kidney growth and delayed progression to ESRD, in particular in CKD stage 4. TRIAL REGISTRATION:ClinicalTrials.gov NCT01377246; EudraCT: 2011-000138-12.

译文

背景: 常染色体显性遗传的多囊卵巢综合征 (ADPKD) 是最常见的遗传决定的肾脏疾病。在受影响的患者中,肾功能可能会逐渐下降到终末期肾病 (ESRD),大约 10% 的 ESRD 患者受到 ADPKD 的影响。生长抑素类似物奥曲肽长效释放 (octreotide-LAR) 减缓疾病早期患者的肾功能恶化。我们评估了奥曲肽-LAR 对因晚期 ADPKD 而处于 ESRD 高风险的 ADPKD 患者的肾脏保护作用。方法和结果: 我们进行了一项内部资助、平行组、双盲、安慰剂对照的三期试验,以评估患有肾小球滤过率 (GFR) 的成人 ADPKD 的奥曲肽-LAR 15-40 ml/min/1.73 m2。参与者被随机分配接受两次肌肉注射,每 28 天注射 20 毫克奥曲肽-LAR (n = 51) 或 0.9% 氯化钠溶液 (安慰剂; n = 49),持续 3 年。中心随机化是 1:1,使用计算机化列表,按中心分层,有无糖尿病或蛋白尿。共同主要的短期和长期结果是 1 年肾脏总体积 (TKV) (计算机断层扫描) 增长和 3 年 GFR (碘海醇血浆清除率) 下降。通过改良的意向治疗进行分析。在 2011年10月11日至 2014年3月20日期间,从 4 个意大利肾脏内科单位招募了患者,并随访至 2017年4月14日。组间基线特征相似。与安慰剂相比,奥曲肽-LAR 在 1 年 (p = 95%) 和 96.8 (10.8 到 182.7) 时从基线减少了 0.027 (422.6 到 150.3) ml 的中位数 (695.0 CI) TKV 增长 ml 在 3 年 (p = 0.002)。肾小球滤过率下降的中位数 (95% CI) 降低 (每年 0.56 [-0.63 至 1.75] ml/min/1.73平方米) 并不显著 (p = 0.295)。TKV 分析根据年龄、性别和基线 TKV 进行了调整。在中位 (IQR) 36 (24 至 37) 个月的随访中, 9 名服用奥曲肽-LAR 的患者和 21 名服用安慰剂的患者的血清肌酐或 ESRD (复合终点) 增加了一倍 (危险比 [HR] [95% CI] 根据年龄、性别进行调整, 基线血清肌酐和基线 TKV: 0.307 [0.127 至 0.742],p = 0.009)。每 4 名接受治疗的患者中就有一个复合终点被阻止。在 63 名慢性肾脏疾病 (CKD) 4 期的患者中,3 名服用奥曲肽-LAR,8 名服用安慰剂,进展至 ESRD (校正 HR [95% CI]: 0.121 [0.017 至 0.866], p = 0.036)。3 名使用安慰剂的患者出现严重的肾囊肿破裂/感染,1 名患者出现严重的尿路感染/阻塞,而 1 名使用奥曲肽-LAR 的患者出现严重的肾囊肿感染。主要的研究局限是样本量小。结论: 在这项研究中,我们观察到在晚期 ADPKD 中,奥曲肽-LAR 减缓了肾脏生长并延缓了 ESRD 的进展,特别是在 CKD 4 期。试验注册: ClinicalTrials.gov NCT01377246; EudraCT: 2011-000138-12。

Octreotide

消化 上消化道出血 药物
概述  :  

奥曲肽是人工合成的天然生长抑素的八肽衍生物,其药理作用与生长抑素相似但作用持续时间更长。本品能抑制胃肠胰内分泌系统的肽以及生长激素的分泌。在动物中,本品抑制生长激素、胰高血糖素和胰岛素的作用较生长抑素更强,且对生长激素和胰高血糖素的选择性更高。其在临床特别是消化系统疾病的应用已越来越广泛。   临床应用 奥曲肽可以用于治疗上消化道出血,包括食管胃底静脉曲张破裂出血以及严重的消化性溃疡大出血等;同时它还可以用于胰腺手术后并

Octreotide 

释义   n.奥曲肽

例句   The synthesis technique of octreotide was optimized and magnified. 优化并放大了奥曲肽的合成技术。

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