Description

The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update is to review the available published evidence and expert advice regarding the clinical management of patients with suspected acute kidney injury in patients with cirrhosis.

Methods

This article provides practical advice for the management of patients with cirrhosis and acute kidney injury based on the best available published evidence. This best practice document is not based on a formal systematic review. This expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through the standard procedures of Clinical Gastroenterology & Hepatology. These Best Practice Advice (BPA) statements were drawn from a review of the published literature and from expert opinion. Since systematic reviews were not performed, these BPA statements do not carry formal ratings of the quality of evidence or strength of the presented considerations.

BEST PRACTICE ADVICE 1

Acute kidney injury (AKI) should be diagnosed when the serum creatinine increases by ≥0.3 mg/dL within 48 hours or is ≥50% from baseline or when the urine output is reduced below 0.5 mL/kg/h for >6 hours.

Best Practice Advice 2

Preventive measures against the development of AKI in cirrhosis include (1) avoidance of potentially nephrotoxic medications like nonsteroidal anti-inflammatory drugs (NSAIDs), (2) avoidance of excessive or unmonitored diuretics or nonselective beta-blockade, (3) avoidance of large-volume paracentesis without albumin replacement, and (4) counseling patients to avoid alcohol use.

Best Practice Advice 3

(A) Investigation is directed to determining the cause of AKI, which can be due to hypovolemic causes (volume responsive, and the most common cause of AKI in patients with cirrhosis); acute tubular necrosis; hepatorenal syndrome with AKI (HRS-AKI) (a functional renal failure that persists despite volume repletion); HRS with acute kidney disease, a type of functional renal failure of <3 months– duration in which criteria for HRS-AKI are not met; or postrenal, which occurs only rarely. (B) The specific type of AKI should be identified through a careful history, physical examination, blood biochemistry, urine microscopic examination, urine chemistry (Na+ and urea) and selected urinary biomarkers, and renal ultrasound.

Best Practice Advice 4

A rigorous search for infection is required in all patients with AKI. A diagnostic paracentesis should be carried out to evaluate for spontaneous bacterial peritonitis; blood and urine cultures and chest radiograph are also required. There is no role for routine prophylactic antibiotics in patients with AKI, but broad-spectrum antibiotics should be started whenever infection is strongly suspected.

Best Practice Advice 5

When AKI is diagnosed, diuretics and nonselective beta-blockers should be held, NSAIDs discontinued, the precipitating cause of AKI treated, and fluid losses replaced, administering albumin 1 g/kg/d for 2 days if the serum creatinine shows doubling from baseline. Urine output, vital signs, and when indicated, echocardiography or CVP (if there is a pre-existing central line) should be used to monitor fluid status.

Best Practice Advice 6

When the serum creatinine remains higher than twice the baseline value despite these measures, treatment of HRS-AKI should be initiated with albumin at a dose of 1 g/kg intravenously on day 1 followed by 20–40 g daily along with vasoactive agents (terlipressin; if terlipressin is not available, either a combination of octreotide and midodrine; or norepinephrine, depending on institutional preferences) and continued either until 24 hours following the return of the serum creatinine level to within ≤0.3 mg/dL of baseline for 2 consecutive days or for a total of 14 days of therapy.

Best Practice Advice 7

Terlipressin should be initiated as a bolus dose of 1 mg every 4–6 hours (total 4–6 mg/d). The dose should be increased to a maximum of 2 mg every 4–6 hours (total 8–12 mg/d) if there is no reduction in serum creatinine at day 3 of therapy by at least 25% compared to the baseline value. Alternatively, clinicians can administer terlipressin by continuous intravenous infusion at a lower starting dose of 2 mg/d, which may reduce ischemic side effects and increase the dose gradually every 24–48 hours up to a maximum dose of 12 mg/d, or reversal of HRS. As per Food and Drug Administration restrictions, terlipressin should not be used in patients with a serum creatinine ≥5 mg/dL, or oxygen saturation of <90%.

Best Practice Advice 8

Oral midodrine when used should be initiated at doses of 7.5 mg and titrated upward to 12.5 mg 3 times daily with octreotide (starting with 100 μg and titrating upward to 200 μg subcutaneously 3 times daily).

Best Practice Advice 9

Norepinephrine should be used as a continuous intravenous infusion at a starting dose of 0.5 mg/h and the dose increased every 4 hours by 0.5 mg/h to a maximum of 3 mg/h with the goal of increasing the mean arterial pressure by ≥10 mm Hg and/or the urine output to >50 mL/h for at least 4 hours.

Best Practice Advice 10

The risks of ischemic side effects of terlipressin and norepinephrine include angina and ischemia of fingers, skin, and intestine. These side effects may be lowered by starting at the lowest dose and gradually titrating upward.

Best Practice Advice 11

Fluid status should be closely monitored because of the risk of pulmonary edema with excessive use of albumin.

Best Practice Advice 12

Renal replacement therapy (RRT) may be used in the management of (A) AKI secondary to acute tubular necrosis; (B) HRS-AKI in potential candidates for liver transplantation (that is, RRT should not be used in patients with HRS-AKI who are not candidates for liver transplantation); and (C) AKI of uncertain etiology in which the need for RRT may be considered on an individual basis.

Best Practice Advice 13

Transjugular intrahepatic portosystemic shunts should not be used as a specific treatment of HRS-AKI.

Best Practice Advice 14

Liver transplantation is the most effective treatment for HRS-AKI. Pharmacotherapy for HRS-AKI before proceeding with liver transplantation may be associated with better post-liver transplantation outcomes. Selected patients with HRS-AKI may require simultaneous liver kidney transplantation based on updated Organ Procurement and Transplantation Network listing criteria.

中文翻译：

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AGA 肝硬化患者急性肾损伤评估和管理的临床实践更新：专家评审

 描述

美国胃肠病学协会 (AGA) 研究所临床实践更新的目的是回顾有关肝硬化患者疑似急性肾损伤患者临床管理的现有已发表证据和专家建议。

 方法

本文根据现有的最佳已发表证据，为肝硬化和急性肾损伤患者的治疗提供实用建议。本最佳实践文件并非基于正式的系统审查。本次专家评审由 AGA 研究所临床实践更新委员会和 AGA 理事会委托并批准，旨在就对 AGA 会员具有高度临床重要性的主题提供及时指导，并接受了临床实践更新委员会的内部同行评审和外部同行评审通过临床胃肠病学和肝病学的标准程序。这些最佳实践建议 (BPA) 声明来自对已发表文献的回顾和专家意见。由于未进行系统审查，这些 BPA 声明并未对证据质量或所提出考虑因素的强度进行正式评级。

 最佳实践建议 1

当血清肌酐在 48 小时内增加≥0.3 mg/dL 或较基线≥50%，或尿量减少至 0.5 mL/kg/h 以下且持续 > 6 小时时，应诊断为急性肾损伤 (AKI)。

 最佳实践建议 2

预防肝硬化发生 AKI 的预防措施包括 (1) 避免使用潜在肾毒性药物，如非甾体类抗炎药 (NSAID)，(2) 避免过量或未监测的利尿剂或非选择性 β 受体阻滞剂，(3) 避免大量使用不补充白蛋白的大量腹腔穿刺术，以及（4）建议患者避免饮酒。

 最佳实践建议 3

(A) 研究旨在确定 AKI 的原因，这可能是由于血容量不足引起的（容量反应性，是肝硬化患者 AKI 的最常见原因）；急性肾小管坏死；伴有 AKI 的肝肾综合征 (HRS-AKI)（一种功能性肾衰竭，尽管容量已补充，但仍持续存在）；伴有急性肾病的 HRS，这是一种持续时间 <3 个月的功能性肾衰竭，不符合 HRS-AKI 的标准；或肾后性，这种情况很少发生。 (B) 应通过仔细询问病史、体格检查、血液生化、尿液镜检、尿液化学（Na+ 和尿素）和选定的尿液生物标志物以及肾脏超声来确定 AKI 的具体类型。

 最佳实践建议 4

所有 AKI 患者都需要严格检查感染情况。应进行诊断性腹腔穿刺术以评估自发性细菌性腹膜炎；还需要进行血液和尿液培养以及胸片检查。对于 AKI 患者，常规预防性抗生素没有作用，但只要强烈怀疑感染，就应开始使用广谱抗生素。

 最佳实践建议 5

当诊断出 AKI 时，应停用利尿剂和非选择性 β 受体阻滞剂，停用 NSAIDs，治疗 AKI 的诱因，并补充液体流失，如果血清肌酐显示较基线翻倍，则给予白蛋白 1 g/kg/d，持续 2 天。应使用尿量、生命体征以及超声心动图或 CVP（如果已有中心静脉导管）监测液体状态。

 最佳实践建议 6

尽管采取了这些措施，当血清肌酐仍高于基线值的两倍时，HRS-AKI 的治疗应在第 1 天开始静脉注射 1 g/kg 白蛋白，随后每天 20-40 g，并与血管活性药物（特利加压素）一起使用。 ；如果没有特利加压素，可联合使用奥曲肽和米多君；或去甲肾上腺素，具体取决于机构偏好），并持续至血清肌酐水平连续 2 天恢复到基线 ≤0.3 mg/dL 以内。或总共 14 天的治疗。

 最佳实践建议 7

特利加压素应以每 4-6 小时 1 mg 的推注剂量开始（总共 4-6 mg/d）。如果治疗第 3 天血清肌酐与基线值相比没有减少至少 25%，则剂量应增加至每 4-6 小时最多 2 mg（总共 8-12 mg/d）。或者，临床医生可以以 2 mg/d 的较低起始剂量连续静脉输注特利加压素，这可以减少缺血性副作用，并每 24-48 小时逐渐增加剂量，直至最大剂量 12 mg/d，或逆转的HRS。根据美国食品和药物管理局的限制，特利加压素不应用于血清肌酐≥5 mg/dL 或氧饱和度<90% 的患者。

 最佳实践建议 8

使用时口服米多君的起始剂量应为 7.5 mg，然后与奥曲肽一起滴定至 12.5 mg，每日 3 次（从 100 μg 开始，滴定至 200 μg，皮下注射，每日 3 次）。

 最佳实践建议 9

去甲肾上腺素应连续静脉输注，起始剂量为 0.5 mg/h，每 4 小时增加 0.5 mg/h，最大剂量为 3 mg/h，目标是使平均动脉压增加 ≥10 mm Hg 和/或尿量> 50 mL/h 至少 4 小时。

 最佳实践建议 10

特利加压素和去甲肾上腺素的缺血性副作用的风险包括心绞痛以及手指、皮肤和肠道缺血。通过从最低剂量开始并逐渐向上滴定，可以降低这些副作用。

 最佳实践建议 11

由于过量使用白蛋白存在发生肺水肿的风险，因此应密切监测液体状态。

 最佳实践建议 12

肾脏替代疗法 (RRT) 可用于治疗 (A) 继发于急性肾小管坏死的 AKI； (B) 潜在肝移植候选者中的HRS-AKI（即不适合肝移植的HRS-AKI患者不应使用RRT）； (C) 病因不明的 AKI，其中 RRT 的需要可根据个人情况考虑。

 最佳实践建议 13

经颈静脉肝内门体分流术不应作为 HRS-AKI 的特异性治疗。

 最佳实践建议 14

肝移植是 HRS-AKI 最有效的治疗方法。进行肝移植前针对 HRS-AKI 的药物治疗可能与更好的肝移植后结局相关。根据更新的器官采购和移植网络列表标准，选定的 HRS-AKI 患者可能需要同时进行肝肾移植。