Acute kidney injury in acute liver failure: a review

Acute liver failure is a rare and often devastating condition consequent on massive liver cell necrosis that frequently affects young, previously healthy individuals resulting in altered cognitive function, coagulopathy and peripheral vasodilation. These patients frequently develop concurrent acute kidney injury (AKI). This abrupt and sustained decline in renal function, through a number of pathogenic mechanisms such as renal hypoperfusion, direct drug-induced nephrotoxicity or sepsis/systemic inflammatory response contributes to increased morbidity and is strongly associated with a worse prognosis. Improved understanding of the pathophysiology AKI in the context of acute liver failure may be beneficial in a number of areas; the development of new and sensitive biomarkers of renal dysfunction, refining prognosis and organ allocation, and ultimately leading to the development of novel treatment strategies, these issues are discussed in more detail in this expert review.     

急性肾损伤与急性心力衰竭

急性肾损伤是指患者血清肌酐水平在48 h内上升25μmol/L(0.3 mg/dl)或较基线水平增高50%,或(和)尿量减少至<0.5 ml·kg~(-1)·h~(-1)并持续6 h以上引起的一组临床综合征.AKI在老年患者中发生率高,临床表现不典型,常易漏诊和误诊,容易进展至急性肾衰竭(acute renal failure,ARF)阶段.     

Acute kidney injury in patients with chronic liver disease

Acute kidney injury(AKI) is a frequent clinical event in patients with liver disease, compounding their prognosis. Furthermore, it is likely that the occurrence of AKI has a detrimental impact on the subsequent renal function and the long-term survival of these patients. Recently, some authors advocated the use of new diagnostic criteria for detecting acute kidney injury in patients with cirrhosis. These criteria are based on the rapidity and extent of the creatinine increase comparing to the basal creatinine and also on the kinetics of diuresis decrease. Although their validity in this population requires further studies to be clearly established, these new criteria could have two advantages:(1) to allow earlier diagnosis of AKI and, thus, hepatorenal syndromefor which earlier intervention could improve patients' survival; and(2) to promote more intensive monitoring of renal function in these patients with high risk of AKI. Finally, recent practice guidelines about the prevention and treatment of general AKI have been published which should be useful in optimising the management of AKI in cirrhotic patients.     

Acute liver injury,acute liver failure and acute on chronic liver failure: A clinical spectrum of poisoning due to Gyromitra esculenta

Gyromitra esculenta, also known as “false morel” is one of the most poisonous mushrooms. This species is found all over the world, growing in coniferous forest in early spring time. Common manifestation of poisoning includes gastrointestinal symptoms which include varied degrees of liver impairment.We describe three cases: acute liver injury, acute liver failure and acute-on-chronic liver failure due to G. esculenta poisoning. At admission patients presented with encephalopathy and features of liver failure. Two of them recovered completely following supportive management while the remaining patient who also had preexisting liver disease developed multiorgan failure and subsequently died.Although a rare occurrence, G. esculenta poisoning should be considered in the differential diagnosis of acute liver failure.     

Acute kidney injury in acute-on-chronic liver failure is different from in decompensated cirrhosis

AIM To evaluate the differences in acute kidney injury(AKI) between acute-on-chronic liver failure(ACLF) and decompensated cirrhosis(DC) patients. METHODS During the period from December 2015 to July 2017, 280 patients with hepatitis B virus(HBV)-related ACLF(HBV-ACLF) and 132 patients with HBV-related DC(HBV-DC) who were admitted to our center were recruited consecutively into an observational study. Urine specimens were collected from all subjects and the levels of five urinary tubular injury biomarkers were detected,including neutrophil gelatinase-associated lipocalin(NGAL), interleukin-18(IL-18), liver-type fatty acid binding protein(L-FABP), cystatin C(CysC), and kidney injury molecule-1(KIM-1). Simultaneously, the patient demographics, occurrence and progression of AKI, and response to terlipressin therapy were recorded. All patients were followed up for 3 mo or until death after enrollment. RESULTS AKI occurred in 71 and 28 of HBV-ACLF and HBV-DC patients, respectively(25.4% vs 21.2%, P = 0.358). Among all patients, the levels of four urinary biomarkers(NGAL, CysC, L-FABP, IL-18) were significantly elevated in patients with HBV-ACLF and AKI(ACLF-AKI), compared with that in patients with HBV-DC and AKI(DC-AKI) or those without AKI. There was a higher proportion of patients with AKI progression in ACLF-AKI patients than in DC-AKI patients(49.3% vs 17.9%, P = 0.013). Fortythree patients with ACLF-AKI and 19 patients with DC-AKI were treated with terlipressin. The response rate of ACLFAKI patients was significantly lower than that of patients with DC-AKI(32.6% vs 57.9%, P = 0.018). Furthermore, patients with ACLF-AKI had the lowest 90 d survival rates among all groups(P 0.001).CONCLUSION AKI in ACLF patients is more likely associated with structural kidney injury, and is more progressive, with a poorer response to terlipressin treatment and a worse prognosis than that in DC patients.     

Acute kidney injury in acute Q fever

Coxiella burnetii infection is not known to involve directly the kidneys. Kidney injury associated with Q fever usually manifests in the setting of chronic infection or endocarditis with development of immune complex deposition. Acute kidney injury (AKI) in the context of acute Q fever infection may be more pathologically heterogeneous. We describe two cases of severe AKI secondary to acute Q fever infection, each with marked differences in pathological characteristics, and clinical course.     

Acute kidney injury and chronic kidney disease after liver transplant: A retrospective observational study

Background and rationaleChronic kidney disease remains an important risk factor for morbidity and mortality among LT recipients, but its exact incidence and risk factors are still unclear.Material and methodsWe carried out a retrospective cohort study of consecutive adults who underwent liver transplant (January 2009–December 2018) and were followed (at least 6 months) at our institution. CKD was defined following the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 Clinical Practice Guidelines. Long-term kidney function was classified into 4 groups: no CKD (eGFR, ≥60 mL/min/1.73 m²), mild CKD (eGFR, 30–59 mL/min/1.73 m²), severe CKD (eGFR, 15–29 mL/min/1.73 m²), and end-stage renal disease (ESRD).ResultsWe enrolled 410 patients followed for 53.2 ± 32.6 months. 39 had CKD at baseline, and 95 developed de novo CKD over the observation period. There were 184 (44.9%) anti-HCV positive, 47 (11.5%) HBsAg positive, and 33 (8.1%) HBV/HDV positive recipients. Recipient risk factors for baseline CKD were advanced age (P = 0.044), raised levels of serum uric acid (P < 0.0001), and insulin dependent DM (P = 0.0034). Early post-transplant AKI was common (n = 95); logistic regression analysis found that baseline serum creatinine was an independent predictor of early post-LT AKI (P = 0.0154). According to our Cox proportional hazards model, recipient risk factors for de novo CKD included aging (P < 0.0001), early post-transplant AKI (P = 0.007), and baseline serum creatinine (P = 0.0002). At the end of follow-up, there were 116 LT recipients with CKD – 109 (93.9%) and 7 (6.1%) had stage 3 and advanced CKD, respectively. Only two of them are undergoing long-term dialysis.ConclusionThe incidence of CKD was high in our cohort of LT recipients, but only a slight decline in kidney function over time was recorded. Prevention of post-transplant AKI will improve kidney function in the long run. We need more studies to analyze the function of kidneys among LT recipients over extended follow-ups and their impact on mortality.     

血清胱抑素C对慢加急性肝衰竭患者肾损伤的早期诊断意义

目的研究血清胱抑素C(CysC)水平对慢加急性肝衰竭(ACLF)患者急性肾损伤(AKI)的早期诊断意义。方法选取2011年8月-2012年10月于本院住院的慢性乙型肝炎相关慢加急性肝衰竭(ACLF)、慢性乙型肝炎(CHB)的患者各60例,同期60例健康者作为对照。肝衰竭患者随访至出院,动态收集患者血清。采用胶乳增强免疫比浊法测定血清CysC水平。通过绘制CysC、肌酐和血钠浓度诊断AKI的受试者工作特征曲线(ROC),获得其曲线下面积(AUC)及最佳临界值。正态分布的计量资料,多组间比较采用单因素方差分析(One-way ANOVA),2组间比较采用双侧t检验;否则,组间比较采用Mann-Whitney U检验。计数资料采用χ2检验。相关分析采用Pearson相关检验。AUC及最佳临界值的计算采用Medcal 12.7.1.0进行分析。结果肝衰竭患者血清CysC水平为(1050±444)ng/ml,显著高于健康对照组(638±275)ng/ml(P=0.016)和CHB组患者(661±225)ng/ml(P=0.028)。ACLF患者血清CysC水平与肌酐水平相关性不显著(r=0.311,P0.05),但与MELD评分呈显著正相关(r=0.529,P0.01)。住院期间,共有8名肝衰竭患者(13.3%)发展为急性肾损伤,多元Logistic回归分析结果显示,血清CysC水平是ACLF患者发生肾损伤的独立影响因素(OR=1.008,P=0.021)。AUC分析显示早期诊断ACLF患者急性肾损伤的血清CysC水平建议值为1210 ng/ml。结论血清CysC检测有助于ACLF伴肌酐水平正常患者住院期间发生急性肾损伤的早期预测。     

The brain in acute on chronic liver failure

Acute-on-chronic liver failure (ACLF) is a newly defined clinical entity with significant morbidity and mortality (~40–90 % at 1 year dependent on need for organ support at presentation). It defines a presentation with acute severe liver injury, often with multiorgan dysfunction, on a background of previously known or unknown cirrhosis. In its severest form, it is almost indistinguishable from acute liver failure, as similarly in around 5 % may rapidly progress to intracranial hypertension and cerebral oedema culminating in coma and/or death. Our understanding of such cerebral sequelae is currently limited to clinical observation, though our knowledge base is rapidly expanding since recent consensus clinical definition and guidance. Moreover, there are now animal models of ACLF and imaging modalities to better characterize events in the brain that occur with ACLF. However, as yet there has been little in the way of interventional study of this condition which are much needed. In this review we dissect existing clinical and experimental data to better characterise the manifestations of ACLF on the brain and allow for the development of targeted therapy as currently the plethora of existing interventions were designed to treat either the effects of cirrhosis or acute liver injury independently.     

Strategies to prevent or reduce acute and chronic kidney injury in liver transplantation

Acute kidney injury (AKI) has a major impact on short‐ and long‐term survival in liver transplant (LT) patients. There is no currently accepted uniform definition of AKI, which would facilitate standardization of the care of patients with AKI and to improve and enhance collaborative research efforts. New promising biomarkers such as neutrophil gelatinase‐associated lipocalin or kidney injury molecule‐1 have been developed for the prevention of delayed AKI treatment. Early dialysis has been shown to be beneficial in patients with AKI stage III according to the classification of the Acute Kidney Injury Network, whereas treatment with loop diuretics or dopamine is associated with worse outcome. The mainstay for the prevention of AKI seems to be avoidance of volume depletion and maintenance of a mean arterial pressure >65 mmHg. Although the aetiology of chronic kidney disease in transplant recipients may be multifactorial, calcineurin‐inhibitor (CNI)‐induced nephrotoxicity significantly contributes to the development of renal dysfunction over time after LT. The delayed introduction of CNI at minimal doses has shown to be safe and effective for the preservation of kidney function. Other strategies to overcome CNI nephrotoxicity include CNI minimization protocols or CNI withdrawal and conversion to mycophenolate mofetil or the mammalian target of rapamycin inhibitor‐based immunosuppressive regimens. However, CNI avoidance may bear a higher rejection risk. Thus, more results from randomized‐controlled studies are urgently warranted to determine which drug combinations are the most beneficial approaches for the potential introduction of CNI‐free immunosuppressive regimens.     

急性/亚急性肝衰竭合并急性肾损伤的临床特征分析

目的初步明确急/亚急性肝衰竭(ALF/SALF)合并急性肾损伤(AKI)患者的临床特征。方法回顾性分析解放军第三〇二医院2015年1月-2016年12月收治的115例ALF/SALF患者临床资料,根据是否发生AKI分为AKI组(n=36)和无AKI组(n=79)。比较两组患者的年龄、性别、肝功能、外周血WBC水平、凝血功能、MELD评分及并发症发生情况等,观察发生AKI患者的预后情况。计量资料组间比较采用t检验,计数资料组间比较采用χ2检验。结果导致ALF/SALF的病因以药物性最为多见(49.57%),其次为不明原因(28.70%)。115例ALF/SALF患者中共36例合并AKI,AKI发生率为31.3%,其中1、2及3期发生率分别为11.30%、14.78%、5.22%。与未发生AKI的患者相比,AKI组患者年龄、WBC、中性粒细胞比值、腹水、腹腔和肺部感染率以及MELD评分均显著增高,血清Alb水平显著降低(P值均<0.05)。发生AKI的患者无效/死亡率明显高于无AKI患者(69.4%vs38.0%,χ2=9.815,P=0.002),且随AKI严重程度的增高,病死率升高,1、2及3期AKI患者无效/死亡的比例分别为61.5%、70.6%和83.3%。结论肝衰竭患者发生AKI时多存在感染或炎症反应,且AKI的发生与肝衰竭患者的病死率相关。     

Vancomycin-induced acute kidney injury after liver transplantation

正To the Editor:Multidrug-resistant Gram-positive bacteria Staphylococcus aureus and Enterococcus species emerge as major pathogens after liver transplantation (LT).Although vancomycin remains the best choice of drug for treating those infections,it is associated with significant nephrotoxicity.Acute kidney injury (AKI) is a common complication in liver recipients due to a combination of factors related to the recipient,donor graft,