Intervention Review
Aldosterone antagonists for preventing the progression of chronic kidney disease
Editorial Group: Cochrane Renal Group
Published Online: 8 JUL 2009
Assessed as up-to-date: 15 AUG 2008
DOI: 10.1002/14651858.CD007004.pub2
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Database Title
Additional Information
How to Cite
Navaneethan SD, Nigwekar SU, Sehgal AR, Strippoli GFM. Aldosterone antagonists for preventing the progression of chronic kidney disease. Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No.: CD007004. DOI: 10.1002/14651858.CD007004.pub2.
Publication History
- Publication Status: New
- Published Online: 8 JUL 2009
Abstract
Background
Treatment with angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) is increasingly used to reduce proteinuria and retard the progression of chronic kidney disease (CKD). But some patients do not attain complete resolution of proteinuria and might have higher aldosterone levels within few months of treatment. The addition of aldosterone antagonists may be beneficial to these patients for reduction of progression of renal damage.
Objectives
We evaluated the benefits and harms of adding aldosterone antagonists in patients with CKD currently treated with ACEi and/or ARB.
Search methods
We searched MEDLINE, EMBASE, CENTRAL, and hand-searched reference lists of textbooks, articles and scientific proceedings for relevant articles.
Selection criteria
Randomised controlled trials (RCTs) and quasi-RCTs comparing aldosterone antagonists in addition to ACEi and/or ARB versus ACEi and/or ARB alone were included.
Data collection and analysis
Two authors independently assessed study quality and extracted data. Statistical analyses were performed using a random effects model and heterogeneity was tested formally using the Cochran Q and I² statistic. Results were expressed as mean difference (MD) for continuous outcomes and risk ratio (RR) for dichotomous outcomes with 95% confidence intervals (CI).
Main results
Ten studies (845 patients) were included. Compared to ACEi and/or ARB plus placebo, non-selective aldosterone antagonists along with ACEi and/or ARB significantly reduced 24 hour proteinuria (7 studies, 372 patients; MD -0.80 g, 95% CI -1.23 to -0.38). There was a significant reduction in both systolic and diastolic blood pressure at the end of treatment with the addition of non-selective aldosterone antagonists to ACEi and/or ARB. This did not translate into an improvement in glomerular filtration rate (5 studies, 306 patients; MD -0.70 mL/min/1.73 m², 95% CI -4.73 to 3.34). There was a significant increase in the risk of hyperkalaemia with the addition of non-selective aldosterone antagonists to ACEi and/or ARB (8 studies, 436 patients; RR 3.06, 95% CI 1.26 to 7.41). In two studies, the addition of selective aldosterone antagonists to ACEi resulted in an additional reduction in 24 hour proteinuria but without any impact on BP and renal function. Data on cardiovascular outcomes, long-term renal outcomes and mortality were not available.
Authors' conclusions
Aldosterone antagonists contribute to reduction of proteinuria in patients with CKD who are already on ACEi and ARB but increase the risk of hyperkalaemia. Available studies are small and have short follow-up. Long-term effects on renal outcomes, mortality and safety are unknown.
Plain language summary
Aldosterone antagonists for preventing the progression of chronic kidney disease
Treatment of proteinuric patients with renin-angiotensin system (RAS) blockers such as angiotensin converting enzyme inhibitors (ACEi) and/or angiotensin receptor blockers (ARB) result in lowering of aldosterone levels during earlier stages of the treatment period. Aldosterone levels will thereafter increases within a few months of therapy with ACEi or ARB, a fact that is known as aldosterone escape phenomenon. This may limit the anti-proteinuric and reno-protective effects of RAS inhibitors. This review of randomised controlled trials showed that addition of aldosterone antagonists results in additional reduction in proteinuria over and above that of inhibition of the RAS but without any impact on kidney function. A higher incidence of hyperkalaemia was noted in these patients. Aldosterone antagonists may be used in small doses in proteinuric patients who are already receiving ACEi or ARB with close monitoring for hyperkalaemia during the treatment period.
摘要
背景
使用醛固酮拮抗劑預防慢性腎疾病的惡化
為了減少蛋白尿和延緩慢性腎臟病的進展，越來越多地使用血管加壓素轉換酉每抑制劑(ACEi)和血管緊張素受體阻滯劑(ARB)的治療。但有些病患的蛋白尿並沒有完全緩解，而且治療數月後可能會有較高的醛固酮濃度。合併使用醛固酮拮抗劑可能有利於減少病患腎損害的進展。
目標
我們主要評估對於慢性腎疾病患者，使用ACEi和ARB加上醛固酮拮抗的冶療，可能帶來的好處與壞處。
搜尋策略
我們搜尋資料包括MEDLINE, EMBASE, CENTRAL，並且以人工的方式搜尋教科書、文章以及科學性手冊的參考文獻清單。
選擇標準
主要包含各項關於比較使用ACEi和ARB加上醛固酮拮抗的冶療或單一使用ACEi和/或 ARB隨機對照試驗 (RCTs) 及準隨機對照試驗 (quasiRCTs) 。
資料收集與分析
分別讓兩位作者各自分析所收集到之文獻，評估其試驗設計是否合乎標準。統計是以隨機效果模式和Cochran Q and I2異質性模式來進行。持續性的效果以平均差(MD)加上95% 信賴區間 (CI) 來表現，對立性的結果以相對風險 (RR) 表現。
主要結論
主要包括了10個研究(845病例)。ACEi和/或ARB加上安慰劑，非選擇性醛固酮拮抗劑合併ACEi和/或ARB的治療, 可以明顯減少 24小時尿蛋白(7項研究，372案例; 平均差 −0.80克，95％CI為 −1.23 到 −0.38)。此項治療可以有效地降低收縮壓和舒張壓。但這並不表示可以改善腎小球過濾率(5項研究，306病例; 平均值 −0.70 mL/min/1.73平方米，95％CI為 −4.73到3.34)。非選擇性醛固酮拮抗劑合併ACEi和/或ARB 的治療會增加高鉀血症的風險(8研究，436例; 相對風險3.06，95％CI為 1.26至7.41)。在兩個研究中，使用選擇性醛固酮拮抗劑加上ACEi的冶療，可以減少 24小時尿蛋白，但對血壓和腎功能沒有任何影響。關於心血管的預後，長期腎病變和死亡率，並沒有數據可尋。
作者結論
對慢性腎病變的患者，合併使用醛固酮拮抗劑與ACEi 和/ARB有助於減少蛋白尿，但會增加高鉀血症的風險。目前的研究規模小，追蹤期限短。針對長期腎疾病的預後，死亡率和安全性，尚未知曉。
翻譯人
本摘要由馬偕醫院張立美翻譯。
此翻譯計畫由臺灣國家衛生研究院 (National Health Research Institutes, Taiwan) 統籌。
總結
在蛋白尿患者，早期使用 腎素血管緊張素系統(RAS)阻滯劑、如ACEi和/或ARB的冶療，可以降低醛固酮的濃度。但冶療數月後，醛固酮的濃度會增加，此現象被稱為醛固酮逃逸現象。這可能會減少 RAS 阻滯劑對抗蛋白尿和腎保護的功能。本次隨機對照試驗顯示，合併使用醛固酮拮抗劑，除了抑制 RAS 外，可以更減少蛋白尿，但對腎功能沒有任何影響。這些病患發生高鉀血症的機率較高。在蛋白尿患者，使用低劑量醛固酮拮抗劑與ACEi和/ARB 時，在洽療過程中應密切監測高鉀血症。