慢性腎臟疾病患者維持較高的血紅素濃度與預後較差有關

作者：Laurie Barclay, MD  
出處：WebMD醫學新聞

　　May 4, 2010 — 根據一項於5月3日內科學誌發表的系統性綜論結果，慢性腎臟疾病（CKD）患者維持較高的血紅素濃度與較差的預後有關。
　　
　　來自紐西蘭基督城Otago大學的Suetonia C. Palmer醫學學士與其同事們寫到，過去的綜合性分析顯示，以紅血球刺激藥物（ESAs）治療CKD增加死亡風險。更多隨機分派研究最近剛完成。
　　
　　這項系統性綜論的目標在於確認ESA治療使用於貧血且罹患CKD患者的臨床預後效果。研究者們搜尋MEDLINE（1966年1月到2009年11月）、EMBASE（1980年1月到2009年11月）、以及考科藍資料庫（至2010年3月），在沒有限制語言下選擇文獻。由2位作者獨立地挑選病患特徵、研究誤差風險、以及ESA治療效果的數據。
　　
　　這項系統性綜論共找到27項臨床研究，共收納10,452位病患。相較於較低的血紅素目標值，較高的血紅素目標值與中風風險較高有關（相對風險[RR]為1.51；95%信賴區間[CI]為1.03-2.21）、高血壓（RR為1.67；95% CI為1.31-2.12）、以及血管通路栓塞（RR為1.33；95% CI為1.16-1.53）。
　　
　　低血紅素目標值有非顯著性較高死亡風險趨勢（RR為1.09；95% CI為0.99-1.20）、嚴重血管事件（RR為1.15；95% CI為0.98-1.33），以及末期腎臟疾病（RR為1.08；95% CI為0.97-1.20）。不同亞群，包括那些CKD不同分期患者，顯示相符的治療效果。
　　
　　這項系統性綜論的限制包括生活品質的選擇性報告，還有臨床試驗中能夠進行ESA劑量對臨床預後評估分析的資訊不足。
　　
　　綜論作者們寫到，CKD患者較高的血紅素目標值會增加中風、高血壓、與血管通路栓塞風險，且可能增加死亡風險、嚴重心血管事件與末期腎臟病變。造成這類傷害的機轉未明，建議以個別病患數據以及固定ESA劑量研究來進行綜合分析才能釐清這些機轉。
　　
　　這項系統性綜論未接受外在資助。部分試驗作者表示與Amgen、Roche、Janssen-Cilag、Sandoz、西安大略大學以及/或是義大利藥物署有相關資金上的往來。


Targeting Higher Hemoglobin Levels in Chronic Kidney Disease Linked to Worse Outcomes

By Laurie Barclay, MD
Medscape Medical News

May 4, 2010 — Targeting higher hemoglobin levels in chronic kidney disease (CKD) is linked to worse outcomes, according to the results of a systematic review reported early release May 3 in the Annals of Internal Medicine.

"Previous meta-analyses suggest that treatment with erythropoiesis-stimulating agents (ESAs) in ...CKD increases the risk for death," write Suetonia C. Palmer, MB, ChB, from the University of Otago, Christchurch, New Zealand, and colleagues. "Additional randomized trials have been recently completed."

The goal of this review was to determine the effects of ESA treatment on clinical outcomes in patients with anemia and CKD. The investigators searched MEDLINE from January 1966 to November 2009, EMBASE from January 1980 to November 2009, and the Cochrane database to March 2010 for appropriate articles, without language restriction. Randomized hemoglobin target trials or trials of ESA vs no treatment or with placebo were independently identified by 2 authors, who also independently extracted data on patient characteristics, study risks for bias, and the effects of ESA treatment.

The reviewers identified 27 trials, enrolling a total of 10,452 patients. Compared with a lower hemoglobin target, a higher hemoglobin target was associated with greater risks for stroke (relative risk [RR], 1.51; 95% confidence interval [CI], 1.03 - 2.21), hypertension (RR, 1.67; 95% CI, 1.31 - 2.12), and vascular access thrombosis (RR, 1.33; 95% CI, 1.16 - 1.53).

There was a nonsignificant trend favoring a lower hemoglobin target in risks for mortality (RR, 1.09; 95% CI, 0.99 - 1.20), serious cardiovascular events (RR, 1.15; 95% CI, 0.98 - 1.33), and end-stage kidney disease (RR, 1.08; 95% CI, 0.97 - 1.20). Various subgroups, including those based on different stages of CKD, showed consistent treatment effects.

Limitations of this review include selective reporting of effects on quality of life and insufficient information reported in trials to permit analysis of the independent effects of ESA dose on clinical outcomes.

"Targeting higher hemoglobin levels in CKD increases risks for stroke, hypertension, and vascular access thrombosis and probably increases risks for death, serious cardiovascular events, and end-stage renal disease," the review authors write. "The mechanisms for harm remain unclear, and meta-analysis of individual-patient data and trials on fixed ESA doses are recommended to elucidate these mechanisms."

This review had no external funding. Some of the study authors have disclosed various financial relationships with Amgen, Roche, Janssen-Cilag, Sandoz, the University of Western Ontario, and/or the Italian Agency for Drugs.

Ann Intern Med. Published online May 3, 2010.