far

作者：Laurie Barclay, MD  
出處：WebMD醫學新聞

　　November 19, 2009 — 根據11月5日線上第1版美國腎臟學會期刊(Journal of the American Society of Nephrology)的兩篇研究結果，不論有無腎臟病，腎功能下降與心血管結果惡化及早逝有關。
　　
　　【第一篇研究：由Shlipak醫師等人執行】
　　加州舊金山退伍軍人醫學中心的Michael G. Shlipak醫師與「Cardiovascular Health Study」這項研究的夥伴寫道，以某一特定時間點定義，慢性腎臟病(Chronic kidney disease，CKD)是心血管疾病的一個重要風險因素，腎功能衰退率是否會造成額外的心血管風險則未知。
　　
　　研究者比較最初7年的腎功能變化和之後8年心衰竭、心肌梗塞、中風、週邊動脈疾病等發生率的關聯。
　　
　　在開始時、第3年、第7年時，測量以胱蛋白C(Cystatin C)為基礎的估計腎絲球過濾速率(GFR)，快速衰退的定義為每年減少超過3mL/minute/1.73 m2。在4,378名適合的研究對象中，有1,083人(25%)發生腎功能快速衰退，這些人每種心血管事件的發生率都顯著較高(全部的P值都< .001)。
　　
　　校正人口統計學因素、心血管疾病風險因素、開始時的腎功能等多變項後，腎功能快速衰退與心衰竭(校正風險比[HR]為1.32；95%信心區間[CI]為1.13 - 1.53)、心肌梗塞(HR為1.48；95% CI為1.21 - 1.83)、週邊動脈疾病(HR為1.67；95% CI為1.02 - 2.75) 有顯著關聯，但是與中風(HR為1.19；95% CI為0.97 - 1.45)沒有關聯。有無CKD並不會改變每項結果迅速衰退的關聯性。
　　
　　研究作者寫道，不論病患有無CKD，腎功能衰退與心衰竭、心肌梗塞、週邊動脈疾病風險較高有關。
　　
　　研究限制包括，無法確認因果關係、在7年追蹤期間僅間接測量最多3次的腎功能、缺乏開始時的白蛋白尿資料。
　　
　　研究作者結論表示，如果經後續研究確認，長時間穩定腎功能的介入方式對於減少心血管疾病風險有額外助益，後續研究應不只考量統計腎功能結果，還要包括功能的持續改變，才可充分瞭解腎病對於心血管後遺症的影響。
　　
　　【第二篇研究：由Matsushita醫師等人執行】
　　第二篇研究由約翰霍普金斯Bloomberg公共衛生學院的Kunihiro Matsushita醫師等人，檢視估計腎絲球過濾速率在3年和9年時的改變，是否與冠狀動脈疾病風險和各種原因的死亡率有關。該研究世代包括13,029名「Atherosclerosis Risk in Communities Study」研究的參與者，該研究是一個於1987至2006年間，對45至64歲人口基礎樣本進行的觀察型研究。
　　
　　校正開始時的共變項，包括以Cox部份風險模式估計腎絲球過濾速率之後，冠狀動脈疾病風險和各種原因的死亡率方面，估計腎絲球過濾速率每年衰退最多(≧5.65%)的前四分之一，比衰退第3高(每年衰退介於0.33%- 0.47%)者顯著高出許多。冠狀動脈心臟病的HR為1.30(95% CI為1.11 - 1.52)、各種原因死亡率的HR為1.22(95% CI為1.06 - 1.41)。對9年估計腎絲球過濾速率改變所進行的分析結果類似。校正第2次估計腎絲球過濾速率測量時的共變項，與冠狀動脈心臟病的關聯變小，但是死亡率方面沒有改變。
　　
　　第3期慢性腎病患者中，最初3年估計腎絲球過濾速率的增加，也與死亡率風險較高有關，作者們認為可能是因為臨床不穩定所致。
　　
　　研究作者寫道，估計腎絲球過濾速率衰退高於平均值，與冠狀動脈心臟病和各種原因死亡率有關。慢性腎病患者的估計腎絲球過濾速率增加，與類似風險增加有關。我們的結果認為，不論是常規照護時的檢測、或腎功能降低患者的檢測，腎功能資料有其臨床價值。
　　
　　研究限制包括，估計腎絲球過濾速率正常範圍採用「Modification of Diet in Renal Disease」公式，可能會因此低估，評估後續變化的公式不精確、肌酸酐值隨著時間隨機波動、缺乏第1次和第2次就診的白蛋白尿資料、估計腎絲球過濾速率小於60 mL/minute/1.73 m2的病患數相對較少、可能有其他干擾因素。
　　
　　研究作者結論表示，校正追蹤期間的共變項之後，腎功能變化和臨床結果風險之間的顯著關聯，觀察到的影響與傳統風險因素的惡化無關。這些資料支持一系列的肌酸酐值測量，門診病患照護通常可以取得，藉由連續的估計腎絲球過濾速率改變而對預後資訊有所幫助，而不倚賴單一次的估計腎絲球過濾速率。
　　
　　美國心臟協會研究者貢獻獎支持Shlipak醫師等人的研究。
　　
　　國家心臟肺臟與血液研究中心支持「Atherosclerosis Risk in Communities S tudy (Matsushita醫師等人)」這項研究。有些研究作者接受Japan Society for the Promotion of Science；國家健康研究中心/國家糖尿病與消化道和腎臟病研究中心；或國家健康研究中心/國家心臟肺臟與血液研究中心等支持。
　　
　　兩篇研究的作者群皆宣告沒有相關財務關係。
　　
　　J Am Soc Nephrol. 線上發表於2009年11月5日。


Declining Renal Function Linked to Worse Cardiovascular Outcomes

By Laurie Barclay, MD
Medscape Medical News

November 19, 2009 — Declining renal function is linked to worse cardiovascular outcomes and early death in individuals with or without kidney disease, according to the results of 2 studies reported in the November 5 Online First issue of the Journal of the American Society of Nephrology.

First Study: Shlipak and Colleagues

"Chronic kidney disease (CKD), defined at a specific time point, is an important risk factor for cardiovascular disease," write Michael G. Shlipak, MD, MPH, from the San Francisco Veterans Affairs Medical Center in San Francisco, California, and colleagues from the Cardiovascular Health Study. "Whether the rate of kidney function decline contributes additional cardiovascular risk is unknown."

The investigators compared the associations of changes in renal function during the first 7 years vs incidence rates during the next 8 years for heart failure, myocardial infarction, stroke, and peripheral arterial disease.

Cystatin C–based estimated glomerular filtration rate (GFR) was assessed at baseline, year 3, and year 7, with rapid decline defined as more than 3 mL/minute/1.73 m2 per year. Rapid decline in kidney function occurred in 1083 (25%) of 4378 eligible participants. These individuals had a significantly higher incidence of each type of cardiovascular event (all P < .001).

Rapid decline in renal function was significantly associated with heart failure (adjusted hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.13 - 1.53), myocardial infarction (HR, 1.48; 95% CI, 1.21 - 1.83), and peripheral arterial disease (HR, 1.67; 95% CI, 1.02 - 2.75) but not with stroke (HR, 1.19; 95% CI, 0.97 - 1.45), after multivariate adjustment for demographic factors, risk factors for cardiovascular disease, and baseline renal function. The presence or absence of CKD did not alter the association of rapid decline with each outcome.

"Declining kidney function associates with higher risk for HF [heart failure], MI [myocardial infarction], and PAD [peripheral arterial disease] among patients with or without CKD," the study authors write.

Limitations of this study include inability to determine causal relationships, indirect measurements of kidney function performed no more than 3 times during 7 years of follow-up, and lack of baseline measurements of albuminuria.

"If replicated in future studies, then these findings suggest that interventions to stabilize kidney function over time could have the additional benefits of decreasing CVD [cardiovascular disease] risk," the study authors conclude. "Future studies should consider not only static measures of kidney function but also ongoing changes in function to appreciate fully the cardiovascular consequences of kidney disease."

Second Study: Matsushita and Colleagues

The second study, by Kunihiro Matsushita, MD, PhD, from Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, and colleagues, examined whether 3- and 9-year changes in estimated GFR are associated with the risk for coronary heart disease and all-cause mortality. The study cohort consisted of 13,029 participants of the Atherosclerosis Risk in Communities Study, a population-based sample of individuals aged 45 to 64 years who were observed from 1987 to 2006.

The risk for coronary heart disease and all-cause mortality were significantly greater in the quartile of participants with the greatest annual decline (? 5.65%) in estimated GFR vs the third quartile (annual decline between 0.33% and 0.47%), after adjustment for baseline covariates including estimated GFR in Cox proportional hazards models. The HR was 1.30 for coronary heart disease (95% CI, 1.11 - 1.52) and 1.22 for all-cause mortality (95% CI, 1.06 - 1.41). Findings were similar for analysis by 9-year changes in estimated GFR. Adjustment for covariates at the second estimated GFR measured attenuated the association with coronary heart disease but not with mortality.

An increase in estimated GFR during the first 3 years among participants with stage III CKD was also associated with higher mortality risk, which the authors attributed to possible clinical instability.

"A steeper than average decline in eGFR [estimated GFR] associates with a higher risk for coronary heart disease and all-cause mortality," the study authors write. "Increases in eGFR among participants with chronic kidney disease associate with similar increased risks....Our results suggest there may be clinical value in sequential kidney function data, often measured in routine care, even among individuals with mildly reduced kidney function."

Limitations of this study include underestimation by the Modification of Diet in Renal Disease equation of estimated GFR in the normal range, imprecision of the equation in evaluating sequential changes, random fluctuations in creatinine levels with time, lack of albuminuria measurement at visits 1 and 2, relatively few participants with estimated GFR of less than 60 mL/minute/1.73 m2, and possible residual confounding.

"The significant association between change in kidney function and risk for clinical outcomes after adjustment for covariates at follow-up suggests the observed effect is independent of the deterioration in traditional risk factors," the study authors conclude. "These data assist in the interpretation of serial serum creatinine measurements, often available in outpatient care, by indicating that change in eGFR contributes additional prognostic information beyond single eGFR measurement."

The study by Shlipak and colleagues was supported by an American Heart Association Established Investigator Award.

The Atherosclerosis Risk in Communities Study (Matsushita and Colleagues) is a collaborative study supported by the National Heart, Lung, and Blood Institute. Some of the study authors were supported by the Japan Society for the Promotion of Science; the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases; or the National Institutes of Health/National Heart, Lung, and Blood Institute.

The authors of both studies have disclosed no relevant financial relationships.

J Am Soc Nephrol. Published online November 5, 2009.