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eGFR、蛋白尿可预测所有年龄的死亡率 Estimated GFR, Albuminuria Predict Mortality Across All Age Groups  

2012-11-03 09:49:16|  分类: 肾科 |  标签: |举报 |字号 订阅

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《美国医学会杂志》10月30日发表的一项Meta分析显示,估算的肾小球滤过率(eGFR)低、蛋白尿高等肾脏指标异常,与所有年龄段的死亡风险和终末期肾病风险均有强烈关联。这项研究同期在肾脏周上发表(JAMA 2012 Oct. 30 [doi:10.1001/jama.2012.16817])。


主要研究者、挪威科技大学的Stein I. Hallan博士指出,与心血管疾病和全因死亡风险均有着紧密联系的慢性肾病风险,一般是通过评估eGFR和蛋白尿水平来判断的。但关于这些指标对老年人死亡风险和慢性肾病风险的预测价值却存在争议,原因是即使在表面上健康的人群中,肾功能也会随着年龄增加而明显下降。一些专家甚至认为GFR下降可能仅仅是自然衰老过程的一部分,因此对于老年人的意义不大。


为了确定eGFR和蛋白尿的预测价值是否随着衰老而下降,Hallan博士及其同事分析了全球46个不同队列的数据,总体受试者年龄范围为18~108岁。其中包括20个北美队列、12个欧洲队列、10个亚洲队列、1个澳大利亚队列和3个多国队列,受试者总数超过200万人,平均随访6年。在这些队列中,26个队列的受试者来自一般人群,8个队列的受试者具有较高的血管疾病风险,其余12个队列的受试者患有慢性肾病。


在随访期间,一般人群和高危队列共死亡112,325人,慢性肾病队列死亡9,037人。在一般人群和高危队列中发生2,766例终末期肾病(ESRD)事件,在慢性肾病队列中发生5,962例ESRD事件。


分析结果显示,尽管受试人群在地域和临床特征方面差异较大,但在所有年龄段中,死亡风险和ESRD事件风险均随着GFR下降而明显上升。


在校正患者性别、种族、心血管病史、血压、血脂水平、体重指数、吸烟状态和糖尿病状态等因素之后,GFR与死亡、ESRD事件风险之间的关联仍然很强。例如,在年龄18~54岁的人群中,eGFR为45 mL/(min?1.73 m2)者相对于80 mL/(min?1.73 m2)者的全因死亡校正危险比(aHR)为3.50,而在年龄≥75岁的人群中,aHR为1.35。关于蛋白尿水平也得出了相似的结果,即在所有年龄的人群中,蛋白尿水平越高均预示死亡和ESRD事件风险增加。


“尽管慢性肾病治疗方法的差异可能也会影响死亡和ESRD风险,但我们的数据支持在eGFR和蛋白尿的基础上对所有年龄的人群给出慢性肾病的通用定义和分期。”


研究者还指出:“上述结果提示,慢性肾病的治疗不能忽视老年患者。既往数据显示,高龄患者eGFR低与典型慢性肾病并发症(如贫血、酸中毒、甲状旁腺功能亢进和高磷血症等)有关。”


这项研究获得了多个政府机构、医学研究委员会和企业的支持。16名作者报告与企业存在多种利益关系。


随刊述评:老年肾损害患者死亡风险高


华盛顿大学肾脏研究所的IAN H. DE BOER博士在随刊述评中指出,医生们在了解上述重要的新数据之后应当认识到,老年肾功能损害患者具有较高的死亡风险。鉴于这一人群的额外死亡常与心血管疾病有关,因此应当采取所有合理的预防措施,包括调整生活方式、使用降压药物、在有蛋白尿的情况下使用肾素-血管紧张素系统抑制剂,以及使用调脂药物。而且,还应当开展更多评估常用降糖治疗对老年患者效果的研究,因为这类患者通常被排除在临床试验之外(JAMA 2012 Oct. 30 [doi: 20.2002/jama.2012.30761])。


BOER博士报告称接受了雅培公司提供的研究资金。




By: MARY ANN MOON, Cardiology News Digital Network


Kidney measures such as low estimated glomerular filtration rate and high albuminuria are strongly associated with mortality and end-stage renal disease across all age groups – even in the elderly, according to a collaborative meta-analysis reported online Oct. 30 in JAMA and presented simultaneously at Kidney Week.


The risk for chronic kidney disease, which in turn is closely allied with the risk for cardiovascular disease and all-cause mortality, typically is gauged by assessing estimated GFR (eGFR) and albuminuria levels. But there has been substantial controversy regarding the accuracy of these measures for predicting mortality and CKD risk in the elderly, because kidney function appears to decline markedly even in apparently healthy people as they age, said Dr. Stein I. Hallan and his associates in the Chronic Kidney Disease Prognosis Consortium.


Some experts even hold that reduced GFR might simply be part of the natural aging process and that the kidneys undergo an inevitable senescence, rendering "normal" markers of kidney function unusable in the elderly, said Dr. Hallan, of St. Olav University Hospital and the Norwegian University of Science and Technology, both in Trondheim, and his colleagues.


To examine whether aging modifies the usefulness of estimated GFR and albuminuria in assessing the risks for mortality and CKD, Dr. Hallan and his associates analyzed data from 46 different cohorts worldwide that included the entire adult age range (18-108 years). The Chronic Kidney Disease Prognosis Consortium includes data on 20 North American, 12 European, 10 Asian, 1 Australian, and 3 multinational cohorts comprising more than 2 million study subjects followed for a mean of 6 years.


Among the study cohorts, 26 involved people from the general population, 8 involved patients at high risk for vascular disease, and the remaining 12 involved patients with CKD.


During follow-up there were 112,325 deaths in the general population and the high-risk cohorts, as well as 9,037 deaths in the CKD cohorts. There were 2,766 end-stage renal disease (ESRD) events in the general population and high-risk cohorts, as well as 5,962 ESRD events in the CKD cohorts.


Both mortality risk and the risk of ESRD events strongly increased with decreasing GFR across all age groups, even though the study populations had widely divergent demographic and clinical characteristics, the investigators said. These risks declined with increasing age (JAMA 2012 Oct. 30 [doi: 10.1001/jama.2012.16817]).


This correlation remained robust when the data were adjusted to account for patient sex, race, history of cardiovascular disease, blood pressure, serum cholesterol levels, body mass index, smoking status, and diabetes status. For example, the adjusted hazard ratio for all-cause mortality in subjects with an eGFR of 45 (compared with 80) mL/min per 1.73 m2 was 3.50 in those aged 18-54 years, and declined with age to 1.35 in those aged at least 75 years.


The findings were similar for albuminuria levels, with high levels predicting mortality and ESRD events across all age groups.


"Although some variation in management of CKD should be considered by age, based on cost and benefits, with respect to risk of mortality and ESRD, our data support a common definition and staging of CKD based on eGFR and albuminuria for all age groups," they said.


These results contradict the concern "that CKD guidelines should be used with caution in older individuals and that low eGFR reflects only natural aging." They also support recommendations that CKD measures be added to mortality risk equations.


In addition, "the strong increase in mortality along with kidney measures at older ages suggests that older adults should not be left out from management strategies of CKD. Previous data show that low eGFR in the very old is associated with classical CKD complications like anemia, acidosis, hyperparathyroidism, and hyperphosphatemia," the researchers said.


This study was supported by a variety of government agencies, medical research councils, and industry sponsors. The 16 authors reported numerous ties to industry sources.


View on The News
Elderly With Kidney Impairment at High Risk of Death


The medical community should conclude from this important new data that older adults with impaired kidney function are at high risk of death.


Since their excess mortality usually takes the form of cardiovascular disease, all appropriate preventive efforts should be taken in this patient population, including lifestyle modifications, blood pressure–lowering medications, renin-angiotensin system inhibitors if proteinuria is present, and lipid-lowering medications.


Furthermore, more study should be undertaken to assess the effects of commonly used glucose-lowering therapies in elderly patients, who have generally been excluded from clinical trials.


DR. IAN H. DE BOER is at the Kidney Research Institute at the University of Washington, Seattle. He reported receiving research funding from Abbott Laboratories. These remarks were taken from his editorial accompanying Dr. Hallan’s report (JAMA 2012 Oct. 30 [doi: 20.2002/jama.2012.30761]).


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