Understanding acute kidney injury (AKI) in liver cirrhosis from the acute-on-chronic liver failure (ACLF) perspective

In the field of hepatology, managing complications in patients with liver diseases is of paramount importance. Among these, acute kidney injury (AKI) in patients with acute-on-chronic liver failure (ACLF) stands out due to its prevalence and significant impact on patient outcomes (1,2). AKI in ACLF differs substantially from AKI in simple liver cirrhosis in its clinical significance (3). AKI developed in ACLF is a manifestation of a multi-organ failure syndrome and is closely associated with a high mortality rate and severe complications.

In particular, AKI in ACLF patients does not respond well to current treatments due to its delayed diagnosis in late stages (4). Its pathophysiology involves complex interactions between the failing liver and other organ systems, leading to rapid and severe clinical deterioration. In contrast, AKI in patients with uncomplicated liver cirrhosis typically arises from isolated renal insults, and while it still poses significant risks, its implications are less dire in general than the multi-organ dysfunction seen in ACLF.

The recent publication of The Asian Pacific Association for the Study of the Liver (APASL) clinical practice guidelines on the management of AKI in ACLF by Maiwall et al. (5) provides a novel and clinically significant framework for addressing this critical issue. Key findings include the high incidence of AKI in ACLF patients, which ranges from 22.8% to 34%, and its severe impact on prognosis and treatment outcomes. The guidelines propose diagnostic criteria for AKI in ACLF, integrating both serum creatinine and urine output, and offer detailed recommendations on risk stratification by PIRO (Predisposition, Injury, Response, Organ failure) model and therapeutic interventions such as the use of albumin, crystalloids and renal replacement therapy (RRT).

The International Club of Ascites (ICA) guidelines have traditionally been the cornerstone of AKI management (6). However, the APASL guidelines introduce innovative criteria that not only consider serum creatinine levels but also incorporate urine output for AKI diagnosis. This dual approach, influenced by the Kidney Disease Improving Global Outcomes (KDIGO) guideline (7), enables high sensitivity and early detection of AKI, which are crucial for timely intervention. Furthermore, the detailed stratification of AKI stage III into stages 3a and 3b based on urine output provides a more granular staging system that can significantly refine treatment plans.

One of the notable features of the guidelines is the pronounced emphasis on the role of albumin in the treatment of AKI. The guidelines provide extensive recommendations on the use of albumin, including specific protocols on the albumin challenge in stage I AKI and the different types of albumin (4–5% vs. 20–25%) to use. At the same time, they recommend caution on excessive use of albumin especially in volume replacement for severe ACLF patients; if possible, the guidelines suggest using guidance according to hemodynamic indices that evaluate fluid responsiveness. In the same vein is an emphasis on monitoring mean arterial pressure (MAP) in patients with hepatorenal syndrome (HRS)-AKI. Utilizing MAP as a critical parameter underscores the importance of precise hemodynamic monitoring in managing these patients effectively. However, various methods proposed by the guideline are not suited for routine evaluation of hemodynamic status, since the inferior vena cava (IVC) collapsibility index or lung ultrasound has not been widely used, and the intra-abdominal pressure measurement is also difficult to use routinely.

APASL further suggests that continuous infusion of terlipressin, an early initiator of vasoconstrictors, is superior to norepinephrine in improving for ACLF patients with HRS-AKI, since the 48-hours delay required for HRS-AKI diagnosis is associated with high probability of dialysis.

The guidelines also provide a detailed and comprehensive approach to RRT for patients with severe AKI, including specific recommendations on the timing of RRT initiation, the use of citrate anticoagulation and detailed weaning protocols.

Despite these significant advancements, the guidelines recognize that the overall recommendations still align closely with pre-existing ICA protocols (8). While the APASL guidelines introduce valuable new perspectives and detailed recommendations, continued research specifically focused on “ACLF-AKI” is essential to build a robust evidence base that can further refine and optimize these guidelines.

The guidelines identify several key areas for future research, including the effects of bile acids on renal ischemia, the impact of gut dysbiosis on AKI, specific biomarkers for AKI in ACLF patients and the definition of renal recovery. While substantial research has been conducted on AKI biomarkers, there is a notable lack of studies specifically on ACLF patients. Such paucity represents a crucial area for further investigation to develop effective, tailored strategies for both diagnosis and treatment.

In conclusion, the APASL clinical practice guidelines on the management of AKI in ACLF represent a pioneering effort to provide comprehensive and practical guidance in this challenging area. By incorporating novel diagnostic criteria, emphasizing specific therapeutic interventions and highlighting areas for future research, the APASL guidelines offer a substantial framework for clinicians managing such complex and high-risk patient population. As research continues to evolve and procure more data, the clinical utility and value of these guidelines are expected to increase, ultimately improving patient outcomes and advancing the standard of care for ACLF patients.

Acknowledgments

Funding: This study was supported by Soonchunhyang University Research Fund.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, HepatoBiliary Surgery and Nutrition. The article did not undergo external peer review.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-24-307/coif). The authors have no conflicts of interest to declare.

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