IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Clinical Research Center for Rare Diseases, Aldo e Cele Daccò, Bergamo, Italy.
Lancet. 2013 Nov 2;382(9903):1485-95. doi: 10.1016/S0140-6736(13)61407-5. Epub 2013 Aug 21.
Autosomal dominant polycystic kidney disease slowly progresses to end-stage renal disease and has no effective therapy. A pilot study suggested that the somatostatin analogue octreotide longacting release (LAR) could be nephroprotective in this context. We aimed to assess the effect of 3 years of octreotide-LAR treatment on kidney and cyst growth and renal function decline in participants with this disorder.
We did an academic, multicentre, randomised, single-blind, placebo-controlled, parallel-group trial in five hospitals in Italy. Adult (>18 years) patients with estimated glomerular filtration rate (GFR) of 40 mL/min per 1·73 m(2) or higher were randomly assigned (central allocation by phone with a computerised list, 1:1 ratio, stratified by centre, block size four and eight) to 3 year treatment with two 20 mg intramuscular injections of octreotide-LAR (n=40) or 0·9% sodium chloride solution (n=39) every 28 days. Study physicians and nurses were aware of the allocated group; participants and outcome assessors were masked to allocation. The primary endpoint was change in total kidney volume (TKV), measured by MRI, at 1 year and 3 year follow-up. Analyses were by modified intention to treat. This study is registered with ClinicalTrials.gov, NCT00309283.
Recruitment was between April 27, 2006, and May 12, 2008. 38 patients in the octreotide-LAR group and 37 patients in the placebo group had evaluable MRI scans at 1 year follow-up, at this timepoint, mean TKV increased significantly less in the octreotide-LAR group (46·2 mL, SE 18·2) compared with the placebo group (143·7 mL, 26·0; p=0·032). 35 patients in each group had evaluable MRI scans at 3 year follow-up, at this timepoint, mean TKV increase in the octreotide-LAR group (220·1 mL, 49·1) was numerically smaller than in the placebo group (454·3 mL, 80·8), but the difference was not significant (p=0·25). 37 (92·5%) participants in the octreotide-LAR group and 32 (82·1%) in the placebo group had at least one adverse event (p=0·16). Participants with serious adverse events were similarly distributed in the two treatment groups. However, four cases of cholelithiasis or acute cholecystitis occurred in the octreotide-LAR group and were probably treatment-related.
These findings provide the background for large randomised controlled trials to test the protective effect of somatostatin analogues against renal function loss and progression to end-stage kidney disease.
Polycystic Kidney Disease Foundation.
常染色体显性多囊肾病（ADPKD）会缓慢进展为终末期肾病，且目前尚无有效的治疗方法。一项初步研究表明，生长抑素类似物奥曲肽长效释放剂（LAR）可能对此病症具有肾脏保护作用。本研究旨在评估奥曲肽-LAR 治疗 3 年对该疾病患者肾脏和囊肿生长及肾功能下降的影响。
我们在意大利的五所医院进行了一项学术性、多中心、随机、单盲、安慰剂对照、平行组试验。肾小球滤过率（GFR）估计值为 40 mL/min/1.73 m²或更高的成年（>18 岁）患者被随机分配（通过电话进行中央分配，使用计算机列表，1:1 比例，按中心分层，分组大小为 4 和 8），接受为期 3 年的治疗，即每 28 天接受两次 20 mg 肌肉内注射奥曲肽-LAR（n=40）或 0.9%氯化钠溶液（n=39）。研究医生和护士了解分配的组别；参与者和结果评估者对分组情况不知情。主要终点是 MRI 测量的总肾体积（TKV）在 1 年和 3 年随访时的变化。分析采用改良意向治疗。本研究在 ClinicalTrials.gov 注册，编号为 NCT00309283。
招募工作于 2006 年 4 月 27 日至 2008 年 5 月 12 日进行。奥曲肽-LAR 组有 38 名患者和安慰剂组有 37 名患者在 1 年随访时有可评估的 MRI 扫描，此时，奥曲肽-LAR 组的 TKV 增加明显低于安慰剂组（分别为 46.2 mL，SE 18.2 和 143.7 mL，26.0；p=0.032）。两组各有 35 名患者在 3 年随访时有可评估的 MRI 扫描，此时，奥曲肽-LAR 组的 TKV 增加（220.1 mL，49.1）的数值小于安慰剂组（454.3 mL，80.8），但差异无统计学意义（p=0.25）。奥曲肽-LAR 组有 37 名（92.5%）参与者和安慰剂组有 32 名（82.1%）参与者至少发生了一次不良事件（p=0.16）。两组的严重不良事件发生率相似。然而，奥曲肽-LAR 组有 4 例胆石症或急性胆囊炎，可能与治疗有关。
这些发现为大规模随机对照试验提供了背景依据，以测试生长抑素类似物对肾功能丧失和进展为终末期肾病的保护作用。
多囊肾病基金会。
