A SYSTEMATIC REVIEW OF ACUTE KIDNEY INJURY IN ACUTE LIVER FAILURE: A CRITICAL CALL TO NEPHROLOGISTS

Introduction:

Acute kidney injury (AKI) in patients with acute liver failure (ALF) is associated with significantly increased mortality and morbidity. The mechanisms underlying AKI in these patients are complex and multifactorial and different from those seen in patients with chronic liver disease. Proposed mechanisms include systemic inflammatory response syndrome (SIRS), bile cast nephropathy, congestive nephropathy, decreased renal perfusion due to elevated intra-abdominal pressure, overaggressive decongestant therapy for hepatic encephalopathy-related raised intracranial pressure, and direct nephrotoxic effects.

Despite these proposed mechanisms, the literature remains sparse on the diverse causes of AKI in ALF and the strategies to mitigate its effects. Therefore, this systematic review aims to estimate the prevalence of AKI among ALF patients, identify risk factors for AKI in this population, evaluate its impact on patient outcomes, and highlight critical gaps in the existing research.

Methods:

We conducted a systematic search of PubMed, Medline, Embase, and Google Scholar using the search term “acute kidney injury in acute liver failure” between January 1, 2000, and June 30, 2024. Studies reporting epidemiological data on AKI in adult ALF patients and written in English were included. Studies focusing on AKI in acute-on-chronic liver failure or cirrhosis were excluded.

The risk of bias in the included studies was assessed using a five-point questionnaire, and studies were rated as high, moderate, or low quality based on the scores achieved. Results were synthesized in accordance with PRISMA guidelines (Figure 1).

Results:

Nine studies (eight retrospective and one prospective), with a total of 6,028 participants were included in the analysis (see Figure 2).

Of these, 3,795 patients (62.9%) were diagnosed with AKI (Figure 3). The studies comprised six single-centre studies, two registries, and one multicentre study. Five studies were rated as high quality, while four were of moderate quality. Eight studies included both acetaminophen- and non-acetaminophen-related ALF, with one study focusing solely on acetaminophen-induced ALF (Figure 4). Other reported etiologies of ALF included autoimmune disorders, viral hepatitis, and others (Figure 5).

The mean age of the study populations was 41.86 ± 4.3 years, with 67% female participants (range: 45.4% to 76.1%). Three studies identified independent risk factors for AKI in ALF patients (Figure 6).

Two studies differentiated between transient AKI (defined as complete renal recovery within 48 hours of onset) and persistent AKI (renal injury persisting beyond 48 hours). In one study, transient AKI occurred in 29.4% of patients, while persistent AKI was observed in 70.5%. Another study reported 9.6% transient AKI and 80.7% persistent AKI. These studies emphasized that persistent AKI, as opposed to transient AKI, is associated with higher mortality and worse outcomes.

Figures 7, 8, and 9 present the outcome results of different studies, showing poorer transplant-free survival rates among patients with AKI compared to those without AKI.

Our study highlights the significant burden of AKI in ALF patients, as well as the variation in AKI outcomes. However, our findings are limited by the lack of data on the specific causes and risk factors for AKI in ALF. The reporting methods in the included studies were heterogeneous, making comparisons difficult. Furthermore, most of the available data originate from Europe and the USA, leaving many regions underrepresented. The causes and risk factors for AKI in ALF may differ substantially in these underrepresented regions, requiring further investigation.

Conclusions:

More than half of patients with acute liver failure (ALF) experience acute kidney injury (AKI), many cases of which may be preventable. Addressing these underlying causes has the potential to significantly reduce the high mortality rates occurring in patients of ALF with AKI. This review emphasizes the urgent need for collaboration between nephrologists and hepatologists to deepen the understanding of the mechanisms, risk factors, and outcomes of AKI in ALF patients. Future research should focus on identifying modifiable risk factors, developing effective prevention and mitigation strategies, and expanding studies to include more geographically diverse populations.

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.