Kunz Regina, Friedrich Chris, Wolbers Marcel, Mann Johannes F E
Basel Institute for Clinical Epidemiology and Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland.
Ann Intern Med. 2008 Jan 1;148(1):30-48. doi: 10.7326/0003-4819-148-1-200801010-00190. Epub 2007 Nov 5.
Reduction of proteinuria is associated with delayed progression of chronic kidney disease. Reports suggest that angiotensin-receptor blockers (ARBs) reduce proteinuria, but results are variable. The relative effect of ARBs and angiotensin-converting enzyme (ACE) inhibitors, and their combined administration, remains uncertain.
To establish the effect of ARBs versus placebo and alternative treatments, and the effect of combined treatment with ARBs and ACE inhibitors, on proteinuria.
English-language studies in MEDLINE and the Cochrane Library Central Register of Controlled Trials (January 1990 to September 2006), reference lists, and expert contacts.
Randomized trials of ARBs versus placebo, ACE inhibitors, calcium-channel blockers, or the combination of ARBs and ACE inhibitors in patients with or without diabetes and with microalbuminuria or proteinuria for whom data were available on urinary protein excretion at baseline and at 1 to 12 months.
Two investigators independently searched and abstracted studies.
Forty-nine studies involving 6181 participants reported results of 72 comparisons with 1 to 4 months of follow-up and 38 comparisons with 5 to 12 months of follow-up. The ARBs reduced proteinuria compared with placebo or calcium-channel blockers over 1 to 4 months (ratio of means, 0.57 [95% CI, 0.47 to 0.68] and 0.69 [CI, 0.62 to 0.77], respectively) and 5 to 12 months (ratio of means, 0.66 [CI, 0.63 to 0.69] and 0.62 [CI, 0.55 to 0.70], respectively). The ARBs and ACE inhibitors reduced proteinuria to a similar degree. The combination of ARBs and ACE inhibitors further reduced proteinuria more than either agent alone: The ratio of means for combination therapy versus ARBs was 0.76 (CI, 0.68 to 0.85) over 1 to 4 months and 0.75 (CI, 0.61 to 0.92) over 5 to 12 months; for combination therapy versus ACE inhibitors, the ratio of means was 0.78 (CI, 0.72 to 0.84) over 1 to 4 months and 0.82 (CI, 0.67 to 1.01) over 5 to 12 months. The antiproteinuric effect was consistent across subgroups.
Most studies were small, varied in quality, and did not provide reliable data on adverse drug reactions. Proteinuria reduction is only a surrogate for important progression of renal failure.
The ARBs reduce proteinuria, independent of the degree of proteinuria and of underlying disease. The magnitude of effect is similar regardless of whether the comparator is placebo or calcium-channel blocker. Reduction in proteinuria from ARBs and ACE inhibitors is similar, but their combination is more effective than either drug alone. Uncertainty concerning adverse effects and outcomes that are important to patients limits applicability of findings to clinical practice.
蛋白尿的减少与慢性肾脏病进展延缓相关。报告提示血管紧张素受体阻滞剂（ARB）可减少蛋白尿，但结果存在差异。ARB与血管紧张素转换酶（ACE）抑制剂的相对疗效及其联合应用的效果仍不明确。
确定ARB对比安慰剂及其他治疗方法，以及ARB与ACE抑制剂联合治疗对蛋白尿的影响。
MEDLINE及考克兰图书馆对照试验中央注册库（1990年1月至2006年9月）中的英文研究、参考文献列表及专家联系方式。
ARB对比安慰剂、ACE抑制剂、钙通道阻滞剂，或ARB与ACE抑制剂联合应用的随机试验，受试者为有或无糖尿病、伴有微量白蛋白尿或蛋白尿的患者，且可获取基线及1至12个月时尿蛋白排泄的数据。
两名研究者独立检索并提取研究资料。
49项研究纳入6181名受试者，报告了72项随访1至4个月的比较结果及38项随访5至12个月的比较结果。与安慰剂或钙通道阻滞剂相比，ARB在1至4个月（平均比值分别为0.57 [95% CI，0.47至0.68]和0.69 [CI，0.62至0.77]）及5至12个月（平均比值分别为0.66 [CI，0.63至0.69]和0.62 [CI，0.55至0.70]）可减少蛋白尿。ARB与ACE抑制剂减少蛋白尿的程度相似。ARB与ACE抑制剂联合应用比单用任一药物能进一步减少蛋白尿：联合治疗对比ARB，1至4个月的平均比值为0.76（CI，0.68至0.85），5至12个月为0.75（CI，0.61至0.92）；联合治疗对比ACE抑制剂，1至4个月的平均比值为0.78（CI，0.72至0.84），5至12个月为0.82（CI，0.67至1.01）。抗蛋白尿作用在各亚组中一致。
多数研究规模小、质量参差不齐，且未提供可靠的药物不良反应数据。蛋白尿减少只是肾衰竭重要进展的替代指标。
ARB可减少蛋白尿，与蛋白尿程度及基础疾病无关。无论对照为安慰剂还是钙通道阻滞剂，其疗效大小相似。ARB与ACE抑制剂减少蛋白尿的效果相似，但联合应用比单用任一药物更有效。关于对患者重要的不良反应及转归的不确定性限制了研究结果在临床实践中的应用。
