Acute kidney injury (AKI) is a prevalent and severe complication observed in over half of critically ill patients [1]. Mortality rates among critically ill patients with AKI are documented to exceed 50%, reaching as high as 80% in cases necessitating renal replacement therapy (RRT) [2]. Sepsis stands as the primary instigator of AKI in intensive care unit (ICU)-admitted patients, contributing to roughly 40% to 50% of all AKI instances [3]. For critically ill patients experiencing hemodynamic instability, continuous RRT (CRRT) stands out as the primary method for dialysis. Despite advances in intensive care, such as CRRT, the mortality rate for critically ill patients with sepsis-induced AKI (SIAKI) undergoing CRRT remains at 50% to 60% [4]. Furthermore, a significant proportion of these patients continue to depend on dialysis upon hospital discharge [5].

Various methods for risk assessment, including disease severity scores and a range of biomarkers, have been integrated into the management of patients with AKI. These tools assess the likelihood of mortality and recovery from dialysis, offering essential insights for clinical decision-making [6]. Nevertheless, widely used prognostic instruments like Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) are criticized for their lack of accuracy and considerable variability in AKI patients [7]. Therefore, there is a need for disease-specific risk stratification tools to predict clinical outcomes, such as mortality and recovery from dialysis, in AKI patients, including critically ill individuals with SIAKI undergoing CRRT.

Sarcopenia, characterized by diminishing muscle mass, strength, and physical function, manifests with a nearly 20% reduction in skeletal muscle mass during the initial 10 days of ICU admission [8]. This loss of muscle mass is linked to prolonged mechanical ventilation and increased mortality [8]. Notably, a substantial number of patients already present with sarcopenia upon ICU admission, and its presence is significantly associated with higher mortality [8–12]. Despite numerous studies exploring the impact of sarcopenia on adverse outcomes in ICU patients, research specifically focused on those with AKI, particularly those undergoing CRRT, is limited. Additionally, investigations into the influence of sarcopenia on recovery from dialysis in AKI patients are scarce. Therefore, in light of the absence of risk stratification tools for assessing outcomes in AKI patients, our aim was to investigate whether the presence of sarcopenia at ICU admission holds prognostic value in predicting mortality and recovery from dialysis in patients with SIAKI undergoing CRRT.

All aspects of research and data collection adhered to the principles of the Declaration of Helsinki and prevailing ethical guidelines, receiving approval from the Institutional Review Board (IRB) of the Pusan National University Yangsan Hospital (No. 05-2022-091). Due to the retrospective nature of the analysis, utilizing de-identified information from medical charts and records, the requirement for informed consent was waived by the IRB.

In the present study, we discovered that 48.5% of critically ill patients with SIAKI undergoing CRRT were sarcopenic, confirming the high prevalence of sarcopenia in this population. Notably, individuals with sarcopenia upon ICU admission experienced significantly higher mortality and a lower rate of recovery from dialysis compared to those without sarcopenia. Furthermore, sarcopenia was found to be an independent predictor for mortality and recovery from dialysis at 28 days for these patients. Importantly, this observation held true independently of other well-known prognostic factors for these patients, including SOFA and APACHE II scores.

This research focused on assessing sarcopenia by measuring skeletal muscle mass using a single cross-sectional CT image at the L3 vertebra. CT imaging is widely acknowledged as the gold standard for evaluating body composition, and assessing cross-sectional muscle areas at specific anatomical sites provides a convenient approach for estimating skeletal muscle mass with CT imaging [16]. The quantitative evaluation of cross-sectional SMA using CT imaging is typically carried out at the L3 level, showing a substantial correlation with overall body muscle mass [14,16,17].

One of the pivotal findings of the current study is that sarcopenia at ICU admission independently predicts mortality at 28 days in critically ill patients with SIAKI undergoing CRRT. Consistent with our findings, previous studies have demonstrated that sarcopenia at ICU admission is independently associated with adverse outcomes, including higher mortality and fewer ventilator-free and ICU-free days [8–12,18]. In the context of critically ill patients with sepsis, a few studies have been reported. Oh et al. [18] found that sarcopenia was associated with both short-term and long-term mortality in 905 patients with septic shock. Lee et al. [19] showed that muscle mass depletion was associated with mortality in 274 patients with sepsis. Regarding patients with AKI, only one study has been reported. Jung et al. [12] demonstrated that muscle mass could be a determining factor for mortality in 2,200 patients with AKI undergoing CRRT. Taken together, our study has demonstrated that sarcopenia is an independent predictor of mortality in a specific group of critically ill patients, namely those with SIAKI undergoing CRRT, contributing to the growing body of research supporting the independent association between sarcopenia and mortality in critically ill patients.

While sarcopenia demonstrates an independent association with mortality in our study subjects, the underlying mechanisms governing these associations remain unclear. In numerous instances, malnutrition and the depletion of muscle mass manifest concomitantly, marked by a reduction in nutrient intake, body weight, and physical activity [18]. These factors collectively contribute to a decline in muscle mass, strength, and physical function. The depletion of muscle mass emerges as a primary factor suppressing amino acid and protein synthesis in response to biological changes in the immune system [18]. This suggests that sarcopenic patients may exhibit heightened vulnerability to newly developed infections and a worsening of existing infection status due to an impaired immune system compared to non-sarcopenic patients [18]. Furthermore, individuals with low muscle mass experience a state of chronic inflammatory conditions, and the promotion of a catabolic state through this chronic inflammation further deteriorates organ functions, including the kidneys. Lastly, hormonal dysregulation observed in AKI patients, including altered levels of growth hormone, testosterone, thyroid hormone, and insulin-like growth factor-1, contributes to a poor clinical outcome by increasing protein degradation and suppressing protein synthesis [12]. The mechanism underlying the causal relationship between sarcopenia and mortality in patients with SIAKI receiving CRRT should be clarified in future clinical and experimental studies.

Another principal finding of our current study is that sarcopenia at ICU admission independently predicts recovery from dialysis at 28 days in critically ill patients with SIAKI undergoing CRRT. To our knowledge, our study is the first to establish the independent relationship between sarcopenia and recovery from dialysis in AKI patients receiving CRRT. Moreover, our results reveal that CKD, SOFA scores, APACHE II scores, and oliguria—previously identified as predictors of recovery from dialysis in CRRT patients—also independently predict recovery from dialysis in SIAKI patients undergoing CRRT. These findings suggest that, beyond traditional predictors, sarcopenia is a predictive factor for recovery from dialysis in SIAKI patients receiving CRRT. The underlying mechanism for the relationship between sarcopenia and recovery from dialysis in our study remains unclear. While the pathophysiology of SIAKI involves tubular necrosis, tubular apoptosis, and endothelial damage, the systemic inflammatory response during sepsis emerges as a key factor in SIAKI development [3]. Therefore, it can be hypothesized that factors worsening inflammation in SIAKI interfere with renal recovery. As mentioned earlier, patients with sarcopenia are in a state of chronic inflammation and may experience an augmented inflammatory reaction during SIAKI [12]. Consequently, this heightened inflammatory response may contribute to a lower likelihood of recovery from dialysis in these patients. We believe that further experimental and clinical research is warranted to explore and elucidate these associations.

Our study has some limitations. Firstly, due to its retrospective design, establishing a causal relationship between sarcopenia and mortality or recovery from dialysis proved challenging, making it difficult to draw definitive conclusions regarding the clinical effects of sarcopenia in our study subjects. Furthermore, while we endeavored to conduct the analysis by incorporating as many variables as possible known to influence study outcomes, data on other potential factors such as nutritional status, pre- and post-SIAKI physical activity levels, and specific treatment modalities that could impact outcomes were not obtained due to the retrospective nature of this study. We believe that future studies including these variables could consolidate the results of our study. Secondly, our study focused on a specific subset of critically ill patients, namely those with SIAKI who underwent CRRT. This introduces a potential selection bias, limiting the generalizability of our findings to other populations of critically ill patients with AKI. Additionally, CT scans were conducted based on clinical indications rather than a standardized study protocol. Consequently, patients with SIAKI who did not undergo CT scans were excluded, creating another source of selection bias. Thirdly, we defined sarcopenia using CT scan-derived skeletal muscle area. While previous studies support the utility of CT scan-derived skeletal muscle area in predicting adverse outcomes in critically ill patients [8–12,18], and its correlation with total muscle mass in healthy subjects [14] and cancer patients [17], this validation was not conducted within our study population. Furthermore, the Asian Working Group for Sarcopenia recommends using dual-energy X-ray absorptiometry (DXA) or bioelectrical impedance analysis (BIA) to measure appendicular muscle mass for assessing sarcopenia [20], suggesting the need for future studies using alternative methods like DXA or BIA to validate our results. Lastly, our study focused exclusively on Korean patients, utilizing Korean-specific SMI thresholds to define sarcopenia. Therefore, caution is warranted when extrapolating our findings to other ethnic groups.

Despite these limitations, our study has several strengths. Firstly, it is the first investigation to date exploring the association between sarcopenia and recovery from dialysis, in addition to mortality, in patients with AKI undergoing CRRT. Secondly, our study included a relatively large cohort of patients (n = 618), comparable to previous studies examining the prognostic value of sarcopenia in critically ill patients. Thirdly, our multivariable analysis spanned various subgroups, incorporating adjustments for significant confounding variables known to impact mortality and recovery from dialysis in AKI patients undergoing CRRT, such as CKD, oliguria, SOFA scores, APACHE II scores, and the interval time from AKI diagnosis to CRRT initiation. Collectively, these findings contribute robust evidence supporting the association between sarcopenia and mortality or recovery from dialysis in patients with SIAKI undergoing CRRT.

In conclusion, the presence of sarcopenia upon ICU admission, assessed by skeletal muscle mass on CT scans, was found to be a predictor of mortality and recovery from dialysis at 28 days in patients with SIAKI undergoing CRRT. Importantly, this association remains independent of commonly used risk factors for adverse outcomes in this population. We suggest that the inclusion of sarcopenia, along with traditional prognostic factors, could assist physicians in risk stratification for adverse outcomes, enabling timely interventions in patients with SIAKI undergoing CRRT. Furthermore, we advocate for future prospective studies to investigate whether interventions targeting the improvement of sarcopenia could influence patient outcomes in this specific patient population.