University Medical Centre Groningen, University of Groningen, Groningen, Netherlands.
Lancet. 2010 Nov 6;376(9752):1543-51. doi: 10.1016/S0140-6736(10)61032-X.
Despite treatment with renin–angiotensin–aldosterone system (RAAS) inhibitors, patients with diabetes have increased risk of progressive renal failure that correlates with albuminuria. We aimed to assess whether paricalcitol could be used to reduce albuminuria in patients with diabetic nephropathy.
In this multinational, placebo-controlled, double-blind trial, we enrolled patients with type 2 diabetes and albuminuria who were receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Patients were assigned (1:1:1) by computer-generated randomisation sequence to receive 24 weeks’ treatment with placebo,1 μg/day paricalcitol, or 2 μg/day paricalcitol. The primary endpoint was the percentage change in geometric mean urinary albumin-to-creatinine ratio (UACR) from baseline to last measurement during treatment for the combined paricalcitol groups versus the placebo group. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00421733.
Between February, 2007, and October, 2008, 281 patients were enrolled and assigned to receive placebo(n=93), 1 μg paricalcitol (n=93), or 2 μg paricalcitol (n=95); 88 patients on placebo, 92 on 1 μg paricalcitol, and 92 on2 μg paricalcitol received at least one dose of study drug, and had UACR data at baseline and at least one timepoint during treatment, and so were included in the primary analysis. Change in UACR was: –3% (from 61 to 60 mg/mmol;95% CI –16 to 13) in the placebo group; –16% (from 62 to 51 mg/mmol; –24 to –9) in the combined paricalcitol groups, with a between-group difference versus placebo of –15% (95% CI –28 to 1; p=0.071); –14% (from 63 to 54 mg/mmol; –24 to –1) in the 1 μg paricalcitol group, with a between-group difference versus placebo of –11%(95% CI –27 to 8; p=0.23); and –20% (from 61 to 49 mg/mmol; –30 to –8) in the 2 μg paricalcitol group, with a between-group difference versus placebo of –18% (95% CI –32 to 0; p=0.053). Patients on 2 μg paricalcitol showed a nearly, sustained reduction in UACR, ranging from –18% to –28% (p=0.014 vs placebo). Incidence of hypercalcaemia,adverse events, and serious adverse events was similar between groups receiving paricalcitol versus placebo.
Addition of 2 μg/day paricalcitol to RAAS inhibition safely lowers residual albuminuria in patients with diabetic nephropathy, and could be a novel approach to lower residual renal risk in diabetes.
Abbott.
尽管使用了肾素-血管紧张素-醛固酮系统（RAAS）抑制剂，患有糖尿病的患者仍有进展性肾功能衰竭的风险增加，这与白蛋白尿有关。我们旨在评估帕立骨化醇是否可用于降低糖尿病肾病患者的白蛋白尿。
在这项多中心、安慰剂对照、双盲试验中，我们招募了正在接受血管紧张素转换酶抑制剂或血管紧张素受体阻滞剂治疗的 2 型糖尿病合并白蛋白尿患者。患者通过计算机生成的随机序列（1:1:1）被分配接受 24 周的安慰剂、1μg/天帕立骨化醇或 2μg/天帕立骨化醇治疗。主要终点是联合帕立骨化醇组与安慰剂组相比，从基线到治疗期间最后一次测量的尿白蛋白与肌酐比值（UACR）的几何平均值的变化百分比。分析按意向治疗进行。这项试验在 ClinicalTrials.gov 注册，编号为 NCT00421733。
在 2007 年 2 月至 2008 年 10 月期间，共纳入了 281 名患者并随机分配接受安慰剂（n=93）、1μg 帕立骨化醇（n=93）或 2μg 帕立骨化醇（n=95）；93 名患者接受安慰剂，92 名接受 1μg 帕立骨化醇，92 名接受 2μg 帕立骨化醇，至少接受一剂研究药物，且在基线和治疗期间至少有一个时间点有 UACR 数据，因此被纳入主要分析。UACR 的变化为：安慰剂组为 -3%（从 61 降至 60mg/mmol；95%CI -16 至 13）；联合帕立骨化醇组为 -16%（从 62 降至 51mg/mmol；-24 至-9），与安慰剂组相比差异为-15%（95%CI -28 至 1；p=0.071）；1μg 帕立骨化醇组为-14%（从 63 降至 54mg/mmol；-24 至-1），与安慰剂组相比差异为-11%（95%CI -27 至 8；p=0.23）；2μg 帕立骨化醇组为-20%（从 61 降至 49mg/mmol；-30 至-8），与安慰剂组相比差异为-18%（95%CI -32 至 0；p=0.053）。接受 2μg 帕立骨化醇治疗的患者 UACR 持续下降，降幅为-18%至-28%（p=0.014 与安慰剂相比）。接受帕立骨醇治疗的患者与安慰剂组的高钙血症、不良事件和严重不良事件的发生率相似。
在 RAAS 抑制的基础上加用 2μg/天帕立骨化醇可安全降低糖尿病肾病患者的残余白蛋白尿，可能是降低糖尿病患者残余肾脏风险的新方法。
以上是对原文的逐字翻译，不保证译文的流畅性。
