慢性腎臟疾病的血紅素治療新目標

作者：Laurie Barclay, MD  
出處：WebMD醫學新聞

　　July 1, 2009 — 根據一項發表在6月22日內科學誌的系統綜論與綜合分析結果顯示，對慢性腎臟疾病（CKD）病患，較好的血紅素治療目標為9.0-12.0 g/dl。
　　
　　來自加拿大Alberta Calgary大學的Fiona M. Clement博士寫到，以紅血球生成素（ESAs）治療CKD的貧血是很常見的。最佳的血紅素治療目標目前還不確定。需要就血紅素治療目標對健康相關生活品質（HQOL）影響力進一步了解。
　　
　　研究者們搜尋從1966年到2006年12月之間的文獻，收集所有隨機分派研究（RCTs），這些研究都使用ESA治療CKD病患的貧血。收納條件包括樣本數目大於30位以上CKD病患、比較epoetin（alfa與beta）或是darbepoetin或是控制組，且報告使用一已經確效評估方式得到的HQOL。以所有可獲得的36項簡版（SF-36）隨機分派研究HQOL數據，針對血紅素維持在低至中間值（9.0-12.0 g/dl）以及高血紅素值（>12.0 g/dl）進行比較。
　　
　　在找到的231篇文獻中，11篇研究是適合納入的，其中9篇使用SF-36。然而，SF-36數據的報告一般而言是不完整的。在SF-36不同的部分，身體功能（加權平均差異[WMD]為2.9；95%信賴區間[CI]為1.3-4.5）、整體健康（WMD為2.7；95% CI為1.3-4.2）、社交功能（WMD為1.3；95% CI為-0.8-3.4）、以及精神健康（WMD為0.4；95% CI為0.1-0.8）都有統計上顯著差異的變化。這些差異都不被認為有臨床上的顯著差異。
　　
　　研究作者們寫到，其研究結果顯示，血紅素高於12.0 g/dl與HQOL很小且臨床上沒有顯著意義的改善。這個與顯著的安全性擔憂都顯示血紅素目標應該介於9.0-12.0 g/dl之間。
　　
　　這項研究的限制包括HQOL不完整的數據，以及綜合分析先天性的限制。
　　
　　研究作者們的結論是，紅血球生成素對於CKD病患來說是非常重要的，特別是對那些正在接受透析的，或是那些沒有治療，處於必須輸血風險的病患。以較高血紅素濃度為治療目標通常可以改善HQOL。然而，我們的系統性綜論顯示支持這項策略的證據很弱，數據是非常少的，僅有兩項RCT以HQOL作為主要試驗終點。
　　
　　綜論作者表示沒有關資金上的往來。部分作者接受加拿大健康服務研究基金會、Alberta Heritage醫療研究基金會、加拿大糖尿病健康預後研究主席、加拿大健康研究機構、以及/或是加拿大腎臟基金會贊助。

New Hemoglobin Target Levels in Chronic Kidney Disease Suggested

By Laurie Barclay, MD
Medscape Medical News

July 1, 2009 — In chronic kidney disease (CKD), the preferred hemoglobin target should be 9.0 to 12.0 g/dL, suggests the results of a systematic review and meta-analysis reported in the June 22 issue of the Archives of Internal Medicine.

"Treatment of anemia in...CKD with erythropoietin-stimulating agents (ESAs) is commonplace," write Fiona M. Clement, PhD, from the University of Calgary in Alberta, Canada, and colleagues. "The optimal hemoglobin treatment target has not been established. A clearer understanding of the health-related quality of life (HQOL) impact of hemoglobin target levels is needed."

The reviewers searched the literature from 1966 through December 2006 for all randomized controlled trials (RCTs) of ESA treatment in patients with anemia associated with CKD. Inclusion criteria were sample size of 30 or more anemic adults with CKD, comparison of epoetin (alfa and beta) or darbepoetin vs control, and reporting of HQOL with use of a validated measure. A systematic review and meta-analysis was performed of all available 36-item short-form (SF-36) RCT data on HQOL for patients treated with low to intermediate (9.0 - 12.0 g/dL) and high hemoglobin target levels (> 12.0 g/dL).

Of 231 articles identified, 11 studies were eligible for inclusion, of which 9 used the SF-36. However, reporting of SF-36 data was generally incomplete. For different domains of the SF-36, there were statistically significant changes in physical function (weighted mean difference [WMD], 2.9; 95% confidence interval [CI], 1.3 - 4.5), general health (WMD, 2.7; 95% CI, 1.3 - 4.2), social function (WMD, 1.3; 95% CI, ?0.8 to 3.4), and mental health (WMD, 0.4; 95% CI, 0.1 - 0.8) domains. None of these changes were thought to be clinically important.

"Our study suggests that targeting hemoglobin levels in excess of 12.0 g/dL leads to small and not clinically meaningful improvements in HQOL," the review authors write. "This, in addition to significant safety concerns, suggests that targeting treatment to hemoglobin levels that are in the range of 9.0 to 12.0 g/dL is preferred."

Limitations of this study include incomplete reporting of HQOL and methodologic limitations inherent in meta-analyses.

"Erythropoietin-stimulating agents are an important aspect of treatment for patients with CKD, especially for those undergoing hemodialysis or who are at risk of requiring blood transfusion without treatment," the review authors conclude. "The cited goal of treatment to a higher hemoglobin target level is often to improve HQOL. However, our systematic review revealed a weak evidence base in support of that strategy, with poorly reported data and only 2 RCTs that examined HQOL as the primary study end point."

The review authors have disclosed no relevant financial relationships. Some of the authors are supported by the Canadian Health Services Research Foundation, the Alberta Heritage Foundation for Medical Research, Canada Research Chair in Diabetes Health Outcomes, Canadian Institutes for Health Research, and/or the Kidney Foundation of Canada.

Arch Intern Med. 2009;169:1104-1112.