vancom 发表于 2016-6-9 10:14:46

[NEJM述评]:危重病患者的肾脏替代治疗—时机是否重要?

                                             

EditorialRenal-Replacement Therapy in the Critically Ill — Does Timing Matter?Ravindra L. Mehta, M.D., D.M.N Engl J Med 2016DOI: 10.1056/NEJMe1606125


Deciding when to initiate renal-replacement therapy (hemodialysis, peritoneal dialysis, or continu- ous hemofiltration) in critically ill patients is challenging. Although there is wide acceptance that dialysis should be started in patients with end-stage renal disease when the glomerular filtration rate is 5 to 10 ml per minute per 1.73 m2 of body-surface area, consensus is lacking for pa- tients with acute kidney injury. The current guide- lines regarding acute kidney injury note that hyperkalemia, acidosis, or diuretic-resistant fluid overload are potentially fatal, yet they leave the decision to initiate dialysis to the judgment of the clinician, resulting in wide variations in interpretation and implementation. Critically ill patients have variable presentations: some have multiorgan failure and underlying coexisting conditions, and, after potentially aggressive volume resuscitation, they may have multiple medications and nutritional needs — all of which factor into how clinicians decide whether to initiate renal-replacement therapy.确定危重病患者何时开始肾脏替代治疗(血液透析、腹膜透析、持续血液滤过)是个难题。终末期肾病患者肾小球滤过率5 – 10 ml/min/1.73 m2体表面积时应当开始透析治疗,这一观点已被广泛接受。但是,急性肾损伤患者开始肾脏替代治疗的时机尚未形成共识。目前有关急性肾损伤的指南认为,尽管高钾血症、酸中毒、利尿剂无效的液体负荷过多可能危及生命,但需要由临床医生判断何时开始透析治疗,从而造成在指南的解读与实施方面存在巨大的差异。危重病患者的临床表现各异:一些患者出现多脏器功能衰竭且存在基础病,在积极的液体复苏治疗后,这些患者可能需要多种药物治疗和营养支持—所有这些因素都影响临床医生开始肾脏替代治疗的决定。
Although many patients with acute kidney injury ultimately recover renal function, the severity of the injury and the clinical course influence the pace and extent of recovery. Consequently, clinicians must distinguish patients who may recover spontaneously from those who will require renal-replacement therapy. In addition, the benefits of renal-replacement therapy must be weighed against its inherent risks. Traditional serum biomarkers are relatively insensitive indicators of when renal-replacement therapy should be initiated. These complex issues have fueled the need for large tri- als to provide evidence that may aid in decision making.尽管许多急性肾损伤患者的肾脏功能最终得以恢复,但是,肾脏损伤的严重程度及临床病程仍然可以影响肾脏功能恢复的速度与程度。因此,临床医生必须能够区分哪些患者的肾脏功能能自行恢复,哪些患者需要肾脏替代治疗。另外,必须权衡肾脏替代治疗的益处及其风险。传统的血清生物标志物对于确定开始肾脏替代治疗的时机而言并不敏感。这些复杂的问题迫切需要大样本试验提供证据,以帮助治疗决策过程。
Gaudry et al. now report in the Journal the primary results of the multicenter Artificial Kid- ney Initiation in Kidney Injury (AKIKI) trial, which took place in 31 intensive care units in France. The trial involved 620 patients with acute kidney injury of Kidney Disease: Improving Global Outcomes (KDIGO) stage 3 (stages are based on serum creatinine level and urine output and range from 1 to 3, with higher stages indicating more severe kidney injury), who required mechanical ventilation, vasopressor therapy, or both but did not have life-threatening complications requiring immediate renal-replacement therapy. Patients were randomly assigned to either immediate renal-replacement therapy (early strategy) or a delayed strategy in which such therapy was initiated if patients had development of severe hyperkalemia, uremia, metabolic acidosis, pulmonary edema, or severe oliguria that persisted for more than 72 hours after randomization. More than half the patients were treated with intermittent hemodialysis. The primary outcome, mortality at 60 days, was similar in the two groups (48.5% in the early-strategy group and 49.7% in the delayed-strategy group, P=0.79); however, 49% of the patients in the delayed-strategy group never received dialysis.Gaudry等人在新英格兰医学杂志报告了法国31个ICU参加的多中心肾脏损伤人工肾脏开始试验(AKIKI)的主要结果。试验共纳入620名急性肾损伤患者,患者符合KDIGO 3级标准(根据血清肌酐水平和尿量分为1级到3级,分级越高,肾脏损伤程度越严重),需要机械通气和(或)升压药物治疗,但没有需要立即开始肾脏替代治疗的危及生命的并发症。患者被随机分为立即肾脏替代治疗组(早期策略组)或者延迟策略组,后者需待患者出现严重高钾血症、尿毒症、代谢性酸中毒、肺水肿或随机分组后严重少尿持续超过72小时,方开始肾脏替代治疗。超过一半的患者接受了间断血液透析治疗。两组患者的主要预后指标即60天病死率相似(早期策略组48.5%,延迟策略组49.7%,P=0.79);然而,延迟策略组有49%的患者从未接受透析治疗。
The avoidance of renal-replacement therapy in the delayed-strategy group raises several important points. The patients who did not need renal-replacement therapy had outcomes similar to those of patients who received it, which has been shown previously. However, there are some caveats about interpreting these results as indicating that delaying renal-replacement therapy is wise. Diuretic use was markedly more common in the delayed-strategy group than in the early-strategy group (36.5% vs. 1.3%). The difference in time to the initiation of renal-replacement therapy between the early-strategy group and the delayed-strategy group — a difference of more than 50 hours — meant that the clinicians involved had time to administer diuretics, treat hyperkalemia and acidosis, and identify patients who did not need renal-replacement therapy. However, this same interval contributed to the worsening metabolic and clinical status of the patients who ultimately did need late renal-replacement therapy, as evidenced by their more frequent need for vasopressors, their worse Sepsis-related Organ Failure Assessment (SOFA) scores, and their more worrisome metabolic measures at the time of the initiation of renal-replacement therapy, as well as by the extended periods of renal-replacement therapy and greater number of hemorrhagic complications in that group. Furthermore, although the differences were nonsignificant when adjusted for baseline severity of illness (Simplified Acute Physiology Score III), the patients who did not receive renal-replacement therapy had the lowest severity-of-illness scores at base- line and had the lowest mortality (37.1%), followed by patients who received therapy early (48.5%) and the patients who received therapy late (61.8%). The delayed-strategy group had a proportionally higher rate of return to adequate urine output for at least 1 day and more days free of renal-replacement therapy than the early-strategy group. However, neither diuresis nor the use or nonuse of renal-replacement therapy reflects measures of renal recovery or whether subsequent chronic kidney disease develops. Given the need for vasopressor therapy in the majority of patients who received renal-replacement therapy, it seems surprising that intermittent hemodialy- sis was the initial method of therapy in 55% of patients and that continuous renal-replacement therapy was used as the sole method in only 30%. Further, the authors did not report markers of therapeutic efficacy or fluid overload that could have influenced outcomes.延迟策略组的部分患者得以避免接受肾脏替代治疗,有几点需要强调。正如既往研究显示,无需肾脏替代治疗的患者其临床预后与接受治疗的患者相似。但是,如果将这一结果解读为延迟肾脏替代治疗是正确的,仍有需要注意之处。与早期策略组相比,延迟策略组利尿剂的使用更为普遍(36.5% vs. 1.3%)。早期与延迟策略组患者开始肾脏替代治疗的时间也不同—相差超过50小时—意味着临床医生有时间使用利尿剂,治疗高钾血症和酸中毒,并确定哪些患者无需接受肾脏替代治疗。但是,对于最终需要接受肾脏替代治疗的患者而言,上述延迟可能导致代谢和临床状况恶化,表现为这些患者更多需要升压药,SOFA评分更差,开始肾脏替代治疗时其代谢指标更糟糕,肾脏替代治疗时间延长,出血并发症更多。另外,尽管根据疾病严重程度(简化急性生理评分SAPS III)基线水平校正后并无显著差异,但未接受肾脏替代治疗的患者疾病严重程度评分的基线水平最低,病死率也最低(37.1%),其后依次为接受早期治疗的患者(48.5%)及接受延迟治疗的患者(61.8%)。与早期策略组相比,延迟策略组患者能够恢复充足尿量且至少持续1天的比例更高,且无肾脏替代治疗天数更长。然而,尿量增多以及是否使用肾脏替代治疗都不能反映肾脏功能恢复情况,也不能反映是否发展为慢性肾病。鉴于接受肾脏替代治疗的多数患者需要使用升压药物治疗,因此,我们意外发现,在55%的患者间断血液透析是初始的治疗模式,而仅有30%的患者始终接受持续肾脏替代治疗。而且,作者并未报告反映疗效的标志物,以及可能影响临床预后的液体负荷过多。
Despite these concerns, this well-designed and carefully conducted multicenter trial provides new data to unravel the complexity of the timing of the initiation of renal-replacement therapy in the context of acute kidney injury. The findings highlight a need for dynamic risk-stratification tools to identify patients who will not need renal-replacement therapy for management of their acute kidney injury. Additional studies are under way and should help in refining strategies for the management of these patients' conditions. Meanwhile, we should focus on the timely application of renal-replacement therapy while considering individual patient characteristics, process-of-care elements, and logistics to achieve therapeutic goals.尽管存在上述顾虑,这项精心设计并实施的多中心试验给我们提供了新的数据,阐明了急性肾损伤患者开始肾脏替代治疗时机的复杂性。试验结果强调需要通过动态风险分层工具鉴别那些无需肾脏替代治疗的急性肾损伤患者。其他一些研究正在进行中,将有助于改进患者的治疗策略。同时,我们应当考虑患者特征、治疗进程以及后勤条件,注意及时应用肾脏替代治疗以达到治疗目标。
Disclosure forms provided by the author are available with the full text of this article at NEJM.org.From the University of California, San Diego, San Diego. This article was published on May 15, 2016, at NEJM.org.
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