新的肾损伤定义可更准确预测死亡率

《胃肠病学》杂志(Gastroenterology)12月刊上发表的一项研究显示，针对肝硬化患者提出的新的急性肾损伤(AKI)共识定义比现行的较严格的定义能更准确地预测该患者人群的30天死亡率和其他不良结局(doi:10.1053/j.gastro.2013.08.051)。

现行的旧的AKI定义要求存在肝肾综合征且血清肌酐水平＞2.5 mg/dL。这意味着肾功能不全不那么严重的患者并不符合该定义且不接受治疗。但最新证据表明，即使是轻度肾功能不全的预后也较差，并且单纯血清肌酐并不能准确反映晚期肝硬化患者的肾功能不全。

因此，国际腹水协会和急性透析质量倡议(ADQI)小组提出，肝硬化患者的AKI应被重新定义为48 h内血清肌酐水平增加≥0.3 mg/dl，或过去6个月内血清肌酐水平相对稳定基线值增加50%，不管最终血清肌酐水平如何。

在这项研究中，多伦多大学胃肠病科的Florence Wong医生及其同事对新定义进行了评估，研究对象是12个北美医学中心2年内收治的337例肝硬化患者，其中287例患者因细菌感染入院，50例在住院期间发生细菌感染。最常见的感染为尿路感染(27%的患者)、自发性细菌性腹膜炎(21%)、皮肤感染(14%)、肺炎(10%)和无明确感染源的自发性菌血症(9%)。

这些患者中约有半数(49%)在住院期间发生至少1次AKI发作。根据新定义，发生AKI的患者的30天死亡率(34%)显著高于不发生AKI的患者(7%)。

大部分发生AKI的患者均仅为1次短暂性发作，并且他们的肾功能完全恢复，但他们在后续30天内的死亡率是无任何AKI的患者的2倍。

新的AKI定义的阴性预测值为93%，阳性预测值为34%。

该研究获美国国立卫生院、国立糖尿病、消化和肾脏疾病研究所、以及国立研究资源中心支持。研究者声明无经济利益冲突。

随刊述评：新的肾损伤定义可预测死亡率

意大利米兰大学内科的Francesco Salerno医生和米兰Maggiore Policlinico医院胃肠病科的Vincenzo La Mura医生表示，上述研究在337例肝硬化住院患者中探讨了AKI的影响。287例患者在入院时存在细菌性感染，93例在住院期间发生细菌性感染。共68例患者死于多器官衰竭，而仅7%的无AKI的患者死亡。在从AKI恢复的患者中，死亡率为15%，在未从AKI恢复的患者中，死亡率为80%。此外，76例(23%)患者发生通常与侵入性操作相关的二次感染。晚期肝病模型评分增加和二次感染是与AKI独立相关的因素。因此，肝硬化合并发生AKI(即使可逆)是生存时间短的强烈预测因素。

这些结果表明，在肝硬化患者中，即使是轻微的肌酐改变(0.3 mg)也具有临床相关性，并且AKI可能是血流动力学不稳定的标志且伴有多器官衰竭和死亡风险。肝硬化患者的血流动力学改变可导致中枢性血容量减少。我们除了应保护患者免于发生感染和AKI之外，还应更加留意那些可增加血清肌酐水平的临床操作。这两名医生声明无相关经济利益冲突。

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By: MARY ANN MOON, Internal Medicine News Digital Network

The newly proposed consensus definition of acute kidney injury in patients with cirrhosis accurately predicts 30-day mortality and other adverse outcomes in this patient population much better than the current, more rigid definition would, according to a report in the December issue of Gastroenterology (doi:10.1053/j.gastro.2013.08.051).

In what they described as the largest prospective study of this topic to date, researchers found that the recently proposed, broader redefinition of acute kidney injury (AKI) correctly identified which patients were likely to die, develop severe complications such as organ failure, or require longer hospitalization, even when the AKI was transient and resolved completely after treatment.

More than half of the patients in this study who had episodes of AKI according to the new definition did not meet the criteria of the old definition. So using the new definition will help identify these high-risk patients at an earlier stage of renal dysfunction, "well before the stringent diagnostic criteria of [the old definition] are reached," when they will have a better treatment response, said Dr. Florence Wong of the division of gastroenterology, University of Toronto, and her associates.

The old definition of AKI required the presence of hepatorenal syndrome, with a serum creatinine level of greater than 2.5 mg/dL. This meant that patients with less severe renal dysfunction didn’t qualify and weren’t treated. But emerging evidence indicates that even mild degrees of renal dysfunction signal a poor prognosis, and that serum creatinine alone doesn’t accurately reflect renal dysfunction in advanced cirrhosis.

So the International Ascites Club and the Acute Dialysis Quality Initiative (ADQI) group proposed that acute kidney injury in cirrhosis should be redefined as an increase in serum creatinine level of 0.3 mg/dL or greater within 48 hours, or a 50% increase in serum creatinine level from a stable baseline reading within the previous 6 months, regardless of final serum creatinine level.

Dr. Wong and her colleagues assessed the new definition in a cohort of 337 cirrhotic patients treated during a 2-year period at 12 North American medical centers who were admitted with a bacterial infection (287 subjects) or who developed a bacterial infection during hospitalization (50 subjects). The most common infections were urinary tract infection (27% of patients), spontaneous bacterial peritonitis (21%), skin infection (14%), pneumonia (10%), and spontaneous bacteremia with no clear source of infection (9%).

Approximately half of these patients (49%) developed at least one episode of AKI during hospitalization. The 30-day mortality was significantly higher for those who developed AKI according to the new definition (34% mortality) than in those who did not (7% mortality), the investigators said.

Most patients who developed AKI had only a transient case, and their renal function completely recovered. Yet their subsequent mortality within 30 days was twice as high as that for patients who didn’t have any AKI.

The negative predictive value of the new definition of AKI was 93%, and the positive predictive value was 34%.

This study was supported in part by the National Institutes of Health, the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Center for Research Resources. No financial conflicts of interest were reported.

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New definition of kidney injury predicts mortality

Renal dysfunction in patients with cirrhosis is often associated with sepsis. This combination involves a very high probability of death. Recently, the concept of acute kidney injury has been proposed to be extended also to renal failure occurring in patients with cirrhosis. AKI should overcome limitations associated with a fixed creatinine threshold, ensure rapid identification of renal dysfunction, and allow timely treatment in patients with hepatorenal syndrome. However, AKI should also overcome the skepticism of those who wish not to abandon previous definitions.

The recent paper of Dr. Wong and her colleagues explored the impact of AKI in 337 hospitalized patients with cirrhosis. Two-hundred eighty-seven patients had bacterial infection at admission, and 93 developed it during hospitalization. Overall, 68 patients died from multiorgan failure, whereas only 7% of patients without AKI died. Mortality ranged from 15% in patients who recovered from AKI to 80% in those who did not. Moreover, 76 patients (23%) developed a second infection, often associated with invasive procedures! An elevated Model for End-Stage Liver Disease score and a second infection were factors independently associated with AKI. Accordingly, the development of AKI in cirrhosis, even if reversible, was shown to be a strong predictor of short survival.

These findings show that, in cirrhosis, even small creatinine changes (0.3 mg) are clinically relevant, and that AKI is probably a hallmark of hemodynamic instability with a risk of multiorgan failure and death. The altered hemodynamics in patients with cirrhosis cause central hypovolemia. Aiming at protecting our patients from infection and AKI, we should also pay more attention to clinical procedures that raise serum creatinine level.

Dr. Francesco Salerno is in the department of internal medicine, at the Policlinico IRCCS San Donato, University of Milan (Italy); Dr. Vincenzo La Mura is with the Fondazione IRCCS Ca'Granda, in the department of gastroenterologia-1 of the Hospital Maggiore Policlinico, Milan. They reported no relevant financial conflicts.