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作者：Lurie Barclay, MD  
出處：WebMD醫學新聞

February 16, 2010 — 根據一項2月3日發表在美國醫學會期刊（JAMA）、以社區為基礎的世代研究，蛋白尿，獨立於估計腎絲球廓清率（eGFR）值之外，可能協助預測慢性腎臟疾病（CKD）病患預後。
　　
　　加拿大亞伯特Calgary大學的Brenda R. Hemmelgarn醫師與亞伯特腎臟疾病網絡的同事們寫到，目前的慢性腎臟疾病分級系統主要是根據eGFR，較低的eGFR與較高的不良預後風險較高有關。雖然蛋白尿也與不良預後有關，但在目前的系統中，這並未被用於估計不良事件風險。
　　
　　這項研究的目的在於透過省級實驗室註冊系統的資料評估GFR降低、蛋白尿、以及不良臨床預後，這些數據包括2002年到2007年之間於加拿大亞伯特監測的eGFR與蛋白尿數據。這項世代研究包括920,985位試驗前不需要腎臟替代療法的成人，以及至少監測過一次門診血清肌酐酸濃度值。
　　
　　以尿液試紙或白蛋白與肌酐酸比值（ACR）來確認蛋白尿。試驗的主要終點是所有原因的死亡率、心肌梗塞與惡化至腎臟衰竭比例。
　　
　　大部分受試者（89.1%）的eGFR值至少60 ml/min/1.73 m2。在後續追蹤（追蹤時間中位數為35個月；範圍為0-59個月）之間，總共有27,959位受試者死亡（3.0%）。較低的eGFR或是較嚴重的蛋白尿，與所有原因死亡率些微較高有關。相較於eGFR介於45-59.9 ml/min/1.73 m2以及正常蛋白排除率受試者，那些以尿液試紙檢測蛋白尿較嚴重的、且eGFR至少60 ml/min/1.73 m2的受試者，校正後死亡率高出2倍（比例分別為7.2；95%信賴區間[CI]為6.6-7.8，相較於2.9；95% CI為2.7-3.0/1000位/年病患；比例比值為2.5；95% CI為2.3-2.7）。
　　
　　以ACR評估蛋白尿時，校正後死亡率是相似的（嚴重蛋白尿為15.9%；95% CI為14.0-18.1而沒有蛋白尿為7.0；95% CI為6.4-7.6/1000位病患/年；比例比值為2.3；95% CI為2.0-2.6）。病患因為心肌梗塞、末期腎臟病變、以及血清肌酐酸濃度上升兩倍住院預後是相當的。
　　
　　這項研究的限制包括觀察性設計；未能捕捉到未使用醫療服務的個體；很難區分急性腎臟衰竭與CKD惡化；相對較短的後續追蹤時間；缺乏使用酒精、香菸、與降血壓藥物數據。
　　
　　研究作者們寫到，特定eGFR值與死亡、心肌梗塞、與惡化至腎臟衰竭風險，會隨著病患高度蛋白尿而獨立地增加。這些發現代表未來CKD分級系統改版實應該納入蛋白尿相關資訊。
　　
　　亞伯特遺產醫療研究基金會（AHFMR）贊助這項研究。部份研究作者獲得加拿大健康研究機構獎學金，這是亞伯特醫療與健康及亞伯特與Calgary大學的合作方案，還有KRESCENT及AHFMR研究獎助。其餘作者們表示已無相關資金上的往來。


Proteinuria May Help Predict Outcomes in Chronic Kidney Disease

By Lurie Barclay, MD
Medscape Medical News

February 16, 2010 — Proteinuria may help predict outcomes in chronic kidney disease (CKD) independent of estimated glomerular filtration rate (eGFR) level, according to the results of a community-based cohort study reported in the February 3 issue of the Journal of the American Medical Association.

"The current staging system for chronic kidney disease is based primarily on ...eGFR with lower eGFR associated with higher risk of adverse outcomes," write Brenda R. Hemmelgarn, MD, PhD, from University of Calgary in Alberta, Canada, and colleagues from the Alberta Kidney Disease Network. "Although proteinuria is also associated with adverse outcomes, it is not used to refine risk estimates of adverse events in this current system."

The goal of the study was to evaluate the association between reduced GFR, proteinuria, and poor clinical outcomes using a province-wide laboratory registry including eGFR and proteinuria measurements from Alberta, Canada, between 2002 and 2007. The study cohort consisted of 920,985 adults who did not require renal replacement therapy at baseline and who had at least 1?outpatient serum creatinine measurement.

Urine dipstick or albumin-creatinine ratio (ACR) was used to identify proteinuria. The main endpoints of the study were all-cause mortality, myocardial infarction, and progression to renal failure.

Most (89.1%) of the participants had an eGFR of at least 60 mL/minute/1.73 m2. During follow-up (median duration, 35 months; range, 0 - 59 months), there were 27,959 deaths (3.0%). Participants with lower eGFRs or heavier proteinuria had a higher fully adjusted rate of all-cause mortality. Compared with participants with an eGFR of 45 to 59.9 mL/minute/1.73 m2 and normal protein excretion, those with heavy proteinuria measured by urine dipstick and an eGFR of at least 60 mL/minute/1.73 m2 had adjusted mortality rates more than twice as high (rate, 7.2; 95% confidence interval [CI], 6.6 - 7.8 vs 2.9; 95% CI, 2.7 - 3.0 per 1000 person-years, respectively; rate ratio, 2.5; 95% CI, 2.3 - 2.7).

When proteinuria was measured by ACR, findings for adjusted mortality were similar (15.9; 95% CI, 14.0 - 18.1 and 7.0; 95% CI, 6.4 - 7.6 per 1000 person-years for heavy and absent proteinuria, respectively; rate ratio, 2.3; 95% CI, 2.0 - 2.6). Findings were also similar for the outcomes of hospitalization with acute myocardial infarction, end-stage renal disease, and doubling of serum creatinine levels.

Limitations of this study include observational design; failure to capture individuals who did not use medical services; difficulty distinguishing acute renal failure from progression of CKD; relatively short follow-up; and lack of data on use of alcohol, tobacco, and antihypertensive medications.

"The risks of mortality, myocardial infarction, and progression to kidney failure associated with a given level of eGFR are independently increased in patients with higher levels of proteinuria," the study authors write. "These findings suggest that future revisions of the classification system for CKD should incorporate information from proteinuria."

The Alberta Heritage Foundation for Medical Research (AHFMR) supported this study. Some of the study authors were also supported by awards from the Canadian Institutes of Health Research, by a joint initiative between Alberta Health and Wellness and the Universities of Alberta and Calgary, and/or by a KRESCENT and AHFMR Fellowship. The remaining study authors have disclosed no relevant financial relationships.

JAMA. 2010;303:423-429.