Abstract
Background
Acute kidney injury (AKI) is a common complication in patients with cirrhosis and is associated with poor outcomes. However, contemporary national data quantifying the impact of AKI severity on mortality and healthcare utilization, as well as potential effect modification across patient subgroups, remain limited.
Methods
We conducted a retrospective cohort study using the 2023 Nationwide Inpatient Sample. Adult hospitalizations with cirrhosis were identified using ICD-10-CM codes. AKI was categorized as no AKI, non–dialysis-requiring AKI, and dialysis-requiring (AKI-D). Survey-weighted multivariable regression models evaluated associations between AKI and in-hospital mortality, length of stay (LOS), and hospital costs. Sensitivity analyses and interaction testing by age and chronic kidney disease (CKD) were performed.
Results
A total of 70,219 unweighted hospitalizations, representing approximately 351,095 nationally, were included. AKI occurred in 32.6% of hospitalizations. In-hospital mortality was higher among patients with AKI compared with those without AKI (13.0% vs. 2.5%, p < 0.001). In adjusted analyses, non–dialysis-requiring AKI was associated with increased mortality (adjusted odds ratio [OR] 4.34, 95% CI 3.99–4.72), while AKI-D was associated with markedly higher mortality (OR 16.37, 95% CI 14.18–18.91). AKI was also associated with increased LOS (ratio 1.45 for non-dialysis AKI; 2.78 for AKI-D) and higher hospital costs (ratio 1.43 and 3.75, respectively). Findings were consistent across multiple sensitivity analyses. Significant interactions were observed by CKD and age, with stronger relative effects in patients without CKD and in younger individuals (p for interaction < 0.001).
Conclusions
AKI is common among hospitalized patients with cirrhosis and is strongly associated with increased mortality and healthcare utilization, with a clear graded relationship by severity. The impact of AKI varies across patient subgroups, highlighting the importance of individualized risk assessment. Strategies targeting early recognition and prevention of AKI may improve outcomes and reduce healthcare burden in this population.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12882-026-05049-y.
Keywords: Acute kidney injury, Cirrhosis, In-hospital mortality, Dialysis-requiring AKI, Health disparities, Hospital outcomes, Length of stay, Healthcare utilization, Administrative data, National inpatient sample
Background
Cirrhosis is a major cause of morbidity and mortality worldwide and is associated with frequent hospitalizations and substantial healthcare utilization [1–3]. Patients with cirrhosis are particularly vulnerable to acute decompensation and multi-organ dysfunction, which contribute significantly to adverse clinical outcomes [4, 5]. Among hospitalized patients, complications such as infection, hemodynamic instability, and renal dysfunction are common and often portend poor prognosis [6, 7].
Acute kidney injury (AKI) is one of the most frequent and clinically significant complications in patients with cirrhosis. The development of AKI reflects complex pathophysiologic processes, including systemic vasodilation, reduced effective arterial blood volume, and activation of neurohormonal pathways, and may manifest as hepatorenal syndrome or intrinsic renal injury [7–9]. Prior studies have consistently demonstrated that AKI in cirrhosis is associated with increased mortality; however, the magnitude of this association varies across clinical settings and patient populations, and the relationship between AKI severity and outcomes remains incompletely characterized.
Despite existing evidence, several important gaps remain. Many prior studies have been limited to single-center cohorts or specific clinical settings, such as intensive care units, which may not reflect broader patient populations [10, 11]. National-level data quantifying the impact of AKI severity on mortality and healthcare utilization are limited. In addition, the extent to which the association between AKI and mortality varies across key patient subgroups, including those with chronic kidney disease (CKD) and differing age profiles, is not well defined. Furthermore, the economic burden associated with AKI in cirrhosis has not been fully characterized in contemporary, nationally representative datasets.
In this study, we used the Nationwide Inpatient Sample to evaluate the association between AKI and in-hospital mortality among patients hospitalized with cirrhosis. We further assessed the impact of AKI severity on healthcare utilization, including length of stay and hospital costs. Additionally, we examined the robustness of these associations across multiple sensitivity analyses and evaluated potential effect modification by CKD status and age. We hypothesized that AKI would be associated with a graded increase in mortality and resource utilization, with variation in effect across patient subgroups.
Methods
Study design and data source
We conducted a retrospective cohort study using the 2023 Nationwide Inpatient Sample (NIS), part of the Healthcare Cost and Utilization Project (HCUP). The NIS is the largest publicly available all-payer inpatient database in the United States and provides nationally representative estimates of hospitalizations [12]. It includes patient- and hospital-level data and incorporates discharge weights to generate national estimates. The dataset is de-identified and publicly available. The institutional review board at BayCare Health System reviewed and approval of this project was not required.
Study population
Adult hospitalizations (age ≥ 18 years) with cirrhosis were identified using International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis codes across all available diagnosis fields. Cirrhosis was defined using codes for alcoholic cirrhosis, biliary cirrhosis, and other cirrhosis-related conditions. Hospitalizations with missing key demographic or outcome variables were excluded.
Exposure definition
The primary exposure was acute kidney injury (AKI), identified using ICD-10-CM codes (N17.x). AKI severity was categorized into three groups: no AKI, AKI not requiring dialysis, and AKI requiring dialysis (AKI-D). Dialysis was identified using ICD-10-PCS procedure codes for renal replacement therapy. This classification allowed evaluation of a graded relationship between AKI severity and clinical outcomes. Definitions of all study variables, including ICD-10-CM and ICD-10-PCS codes used to identify exposures, outcomes, comorbidities, and cirrhosis-related complications, are provided in Supplementary Table 1.
Outcomes
The primary outcome was in-hospital mortality, defined using the HCUP variable indicating death during hospitalization. Secondary outcomes included length of stay (LOS) and hospital cost. Hospital costs were estimated by applying HCUP-provided cost-to-charge ratios to total hospital charges. LOS was analyzed as a continuous variable and log-transformed to account for right-skewed distribution.
Covariates
Covariates included demographic characteristics (age and sex), socioeconomic factors (primary payer and median household income quartile), and admission characteristics (elective status and emergency department admission). Clinical comorbidities, including diabetes mellitus, congestive heart failure, hypertension, and chronic kidney disease, were identified using ICD-10-CM codes. Cirrhosis-related complications, including ascites, hepatic encephalopathy, and varices, were also included to account for liver disease severity. Sepsis was identified using ICD-10-CM codes (A40–A41) and included as a covariate in adjusted models.
Statistical analysis
All analyses accounted for the complex survey design of the NIS using discharge weights (DISCWT), stratification (NIS_STRATUM), and clustering (HOSP_NIS) to generate nationally representative estimates. Continuous variables were summarized as means or medians, and categorical variables as proportions. Survey-weighted multivariable logistic regression models were used to assess the association between AKI and in-hospital mortality. Linear regression models with log-transformed outcomes were used to evaluate LOS and hospital costs, exponentiated coefficients were interpreted as relative percentage differences.
Sensitivity analyses were performed to assess the robustness of findings, including removal of emergency department admission from the model, restriction to non-elective admissions, exclusion of patients with sepsis, and restriction to hospitalizations with cirrhosis as the primary diagnosis. Interaction analyses were conducted to evaluate effect modification by age and chronic kidney disease. Statistical significance was defined as a two-sided p-value < 0.05. All analyses were performed using R software (version 4.5.1; R Foundation for Statistical Computing, Vienna, Austria) [13].
Results
Baseline characteristics
A total of 70,219 unweighted hospitalizations with cirrhosis were identified, representing approximately 351,095 hospitalizations nationwide after applying survey weights. Acute kidney injury was present in 114,620 (32.6%) weighted hospitalizations. Patients with AKI were older than those without AKI (mean age 61.5 vs. 58.6 years, p < 0.001) and had a slightly lower proportion of females (38.2% vs. 40.3%, p = 0.02).
Patients with AKI also demonstrated greater disease severity. Cirrhosis-related complications were more common in the AKI group, including ascites (15.5% vs. 10.3%), hepatic encephalopathy (19.7% vs. 10.0%), and slightly lower prevalence of varices (21.5% vs. 23.4%) (all p < 0.05). Baseline characteristics were presented in Table 1.
Table 1.
Baseline characteristics of hospitalizations with cirrhosis, stratified by AKI status
| Characteristic | No AKI (n = 47,295) | AKI (n = 22,924) | p-value |
|---|---|---|---|
| Age, mean (SE) | 58.6 (0.10) | 61.5 (0.14) | < 0.001 |
| Female, % | 40.3% | 38.2% | 0.02 |
| In-hospital mortality, % | 2.49% | 13.04% | < 0.001 |
| Length of stay, median (IQR), days | 4 (2–7) | 6 (3–11) | < 0.001 |
| Hospital cost, median (IQR), $ | 12,242 (7,710 − 20,518) | 18,920 (10,940 − 35,710) | < 0.001 |
| Primary payer, % | < 0.001 | ||
| Medicare | 41.4% | 46.9% | |
| Medicaid | 26.5% | 22.4% | |
| Private insurance | 22.0% | 22.2% | |
| Self-pay | 5.7% | 4.2% | |
| No charge | 0.5% | 0.3% | |
| Other | 3.7% | 3.7% | |
| Median household income quartile, % | 0.01 | ||
| Q1 (lowest) | 32.9% | 31.7% | |
| Q2 | 26.3% | 26.3% | |
| Q3 | 22.1% | 23.0% | |
| Q4 (highest) | 14.6% | 15.2% | |
| Missing | 4.1% | 3.8% | |
| Cirrhosis-related complication, % | |||
| Ascites | 10.3% | 15.5% | < 0.001 |
| Hepatic encephalopathy | 10.0% | 19.7% | < 0.001 |
| Varices | 23.4% | 21.5% | 0.03 |
Table 1 describes the baseline demographic, clinical, and socioeconomic characteristics of cirrhosis hospitalizations stratified by AKI status. Values are reported as survey-weighted means, medians, or percentages, as appropriate. Costs were estimated using HCUP cost-to-charge ratios.
Association of AKI with in-hospital mortality
In multivariable analysis adjusting for demographic characteristics, socioeconomic factors, admission characteristics, comorbidities, cirrhosis-related complications, and sepsis, AKI remained strongly associated with increased in-hospital mortality (Table 2). Compared with patients without AKI, non–dialysis-requiring AKI was associated with a more than fourfold increase in mortality (adjusted odds ratio [OR] 4.34, 95% CI 3.99–4.72), while dialysis-requiring AKI was associated with over a sixteen fold increase (OR 16.37, 95% CI 14.18–18.91).
Table 2.
Adjusted association of AKI with in-hospital mortality
| Variable | Adjusted OR | 95% CI | p-value |
|---|---|---|---|
| AKI severity | < 0.001 | ||
| No AKI | Reference | — | — |
| AKI (non-dialysis) | 4.34 | 3.99–4.72 | < 0.001 |
| AKI requiring dialysis (AKI-D) | 16.4 | 14.2–18.9 | < 0.001 |
| Sepsis | 4.90 | 4.36–5.51 | < 0.001 |
| Age (per year) | 1.02 | 1.02–1.02 | < 0.001 |
| Female (vs. male) | 0.96 | 0.90–1.03 | 0.29 |
| Primary payer | |||
| Medicaid (vs. Medicare) | 0.80 | 0.72–0.89 | < 0.001 |
| Private insurance | 0.90 | 0.81–1.00 | 0.04 |
| Self-pay | 1.33 | 1.14–1.55 | < 0.001 |
| Other | 1.27 | 1.08–1.50 | 0.004 |
| Median household income quartile | 0.001 | ||
| Q1 (lowest) | Reference | — | — |
| Q2 | 0.77 | 0.63–0.94 | 0.01 |
| Q3 | 0.72 | 0.60–0.88 | 0.001 |
| Q4 (highest) | 0.68 | 0.56–0.82 | < 0.001 |
| Admission characteristics | |||
| Admission via emergency department | 0.65 | 0.59–0.72 | < 0.001 |
| Comorbidities | |||
| Diabetes mellitus | 0.72 | 0.64–0.80 | < 0.001 |
| Congestive heart failure | 0.89 | 0.82–0.98 | 0.02 |
| Hypertension | 0.68 | 0.62–0.74 | < 0.001 |
| Chronic kidney disease | 0.56 | 0.52–0.62 | < 0.001 |
| Cirrhosis-related complications | |||
| Ascites | 1.34 | 1.21–1.49 | < 0.001 |
| Hepatic encephalopathy | 2.73 | 2.53–2.95 | < 0.001 |
| Varices | 0.92 | 0.84–0.99 | 0.04 |
Table 2 evaluates the independent association between AKI and in-hospital mortality after adjustment for demographic and socioeconomic factors. Survey-weighted multivariable logistic regression evaluating the independent association between AKI severity and in-hospital mortality among cirrhosis hospitalizations, adjusted for demographic characteristics, socioeconomic factors, admission characteristics, comorbidities, cirrhosis-related complications, and sepsis.
Sepsis was independently associated with increased mortality (OR 4.90, 95% CI 4.36–5.51). Increasing age was also associated with higher mortality, while higher household income was associated with lower mortality. Several comorbidities, including diabetes, hypertension, and chronic kidney disease, were associated with lower mortality. These findings likely reflect residual confounding, coding bias, survivor bias, or differences in baseline disease severity and treatment patterns. Importantly, sensitivity analyses excluding comorbidities yield consistent results, reinforcing that the association between AKI and mortality is robust and not driven by model specification.
Among cirrhosis-related complications, hepatic encephalopathy demonstrated the strongest association with mortality (OR 2.73, 95% CI 2.53–2.95), followed by ascites (OR 1.34, 95% CI 1.21–1.49). Findings were consistent in a parsimonious model with limited covariate adjustment (Supplementary Table 2), demonstrating a similar graded association between AKI severity and in-hospital mortality.
Length of stay and hospital cost
AKI was associated with increased healthcare utilization (Table 3). Non–dialysis-requiring AKI was associated with a 45% increase in length of stay (ratio 1.45, 95% CI 1.43–1.47), while dialysis-requiring AKI was associated with nearly a threefold increase (ratio 2.78, 95% CI 2.64–2.92).
Table 3.
Adjusted association of AKI severity with length of stay and cost
| A. Length of stay | |||
| Variable | Ratio (exp β) | 95% CI | Interpretation |
| AKI (non-D) | 1.45 | 1.43–1.47 | + 45% LOS |
| AKI-D | 2.78 | 2.64–2.92 | ~ 3× LOS |
| B. Hospital cost (CCR-adjusted) | |||
| Variable | Ratio (exp β) | 95% CI | Interpretation |
| AKI (non-D) | 1.43 | 1.41–1.46 | + 43% cost |
| AKI-D | 3.75 | 3.53–3.98 | 3.7× cost |
Table 3 quantifies the impact of acute kidney injury (AKI) severity on hospital resource utilization, including length of stay (LOS) and total hospital costs. Survey-weighted multivariable regression models assessing the association of AKI severity with length of stay and total hospital costs, adjusted for demographic, socioeconomic, clinical, and cirrhosis-related factors. Results are presented as exponentiated coefficients representing relative differences.
Similarly, AKI was associated with increased hospital costs. Non–dialysis-requiring AKI was associated with a 43% increase in cost (ratio 1.43, 95% CI 1.41–1.46), while dialysis-requiring AKI was associated with approximately a 3.7-fold increase (ratio 3.75, 95% CI 3.53–3.98).
Sensitivity analyses
Sensitivity analyses demonstrate consistent findings across multiple model specifications (Supplementary Table 3). Excluding emergency department admission from the model did not materially change the results (AKI non–dialysis OR 4.79, 95% CI 4.40–5.21; AKI-D OR 20.8, 95% CI 18.1–24.0). Similarly, restricting the cohort to non-elective admissions yielded slightly higher effect estimates (AKI non–dialysis OR 4.92, 95% CI 4.51–5.36; AKI-D OR 21.9, 95% CI 19.0–25.3).
Excluding patients with sepsis resulted in similar effect estimates (AKI non–dialysis OR 4.52, 95% CI 4.13–4.95; AKI-D OR 19.5, 95% CI 16.8–22.7). In analyses restricted to hospitalizations with cirrhosis as the primary diagnosis, the magnitude of association was substantially higher (AKI non–dialysis OR 7.98, 95% CI 6.84–9.30; AKI-D OR 35.5, 95% CI 28.3–44.6).
The consistency of the association between AKI and in-hospital mortality across multiple sensitivity analyses is illustrated in Fig. 1. Effect estimates remained stable across all model specifications, including exclusion of sepsis, removal of admission-related variables, and restriction to primary cirrhosis hospitalizations, supporting the robustness of the observed association.
Fig. 1.
Association between AKI severity and in-hospital mortality across primary and sensitivity analyses
Figure 1 demonstrates the association between AKI severity and in-hospital mortality across primary and sensitivity analyses. The consistency of effect estimates across models, including exclusion of sepsis, comorbidities, and CKD, as well as restriction to primary cirrhosis hospitalizations, supports the robustness of the observed association and suggests that findings are not driven by residual confounding or model specification.
Interaction analyses
Significant interactions were observed between AKI and both chronic kidney disease (CKD) and age (Supplementary Table 4). The association between AKI and mortality was attenuated among patients with CKD compared with those without CKD (p for interaction < 0.001). Similarly, the relative effect of AKI was weaker among patients aged ≥ 65 years, with a stronger association observed in younger patients (p for interaction < 0.001).
The interaction between AKI severity and CKD status is visually demonstrated in Fig. 2. The relative increase in mortality associated with AKI was attenuated among patients with CKD, whereas a steeper gradient was observed among patients without CKD, indicating a stronger association between AKI and mortality in those without underlying kidney disease.
Fig. 2.
Effect modification of the association between AKI severity and in-hospital mortality by CKD status
Figure 2 illustrates the effect modification of the association between AKI severity and in-hospital mortality by CKD status. Odds ratios are shown relative to patients without AKI within each subgroup. The steeper increase in mortality observed among patients without CKD indicates a stronger association between AKI and mortality compared with those with CKD.
Discussion
In this nationally representative study of hospitalizations with cirrhosis, acute kidney injury (AKI) was common and strongly associated with adverse clinical outcomes. Approximately one-third (32.7%) of hospitalizations were complicated by AKI, which was associated with a marked increase in in-hospital mortality (13.0% vs. 2.5%), longer length of stay, and higher hospital costs. A clear graded relationship was observed, with progressively higher mortality risk from non–dialysis-requiring AKI (adjusted OR 4.34) to dialysis-requiring AKI (adjusted OR 16.4). Importantly, these findings were consistent across multiple sensitivity analyses and model specifications, supporting the robustness of the observed association. We also identified significant heterogeneity in the association between AKI and mortality by chronic kidney disease (CKD) status and age, highlighting important differences in risk across patient subgroups. Together, these findings highlight AKI as a key factor associated with both clinical outcomes and healthcare utilization in cirrhosis.
The strong association between AKI and mortality in cirrhosis likely reflects the complex pathophysiology of advanced liver disease. Cirrhosis is characterized by systemic vasodilation, reduced effective arterial blood volume, and activation of neurohormonal pathways that predispose to renal hypoperfusion [14, 15]. In this setting, AKI often represents a manifestation of multi-organ dysfunction, including processes such as hepatorenal syndrome and ischemic acute tubular necrosis, rather than an isolated renal insult. The markedly elevated mortality observed in dialysis-requiring AKI suggests that progression to severe kidney injury reflects advanced circulatory failure and limited physiologic reserve. These findings reinforce the concept that AKI in cirrhosis is both a marker of disease severity and a mediator of worse outcomes.
Our findings extend prior literature in several important ways. While previous studies have demonstrated an association between AKI and mortality in cirrhosis, many have been limited to single-center cohorts or specific clinical settings. For example, a single-center study of 179 hospitalized cirrhosis patients reported an AKI prevalence of 27.9%, with a 64% mortality rate among affected patients, accounting for 41% of all in-hospital deaths [16]. Similarly, Staufer et al. [17] and Allegretti et al. [18] evaluated critically ill cirrhosis patients requiring renal replacement therapy and demonstrated extremely high mortality, highlighting the severe prognosis associated with advanced kidney injury in highly selected ICU populations. By leveraging a large, nationally representative dataset, our study provides contemporary estimates of the burden and impact of AKI across diverse hospital settings.
The magnitude of association observed in this study, particularly for dialysis-requiring AKI, was striking, with effect estimates that appear higher than those reported in prior general cirrhosis cohorts, where AKI has typically been associated with approximately 2–6-fold increases in mortality depending on severity [19–21]. These findings underscore the severe prognostic implications of advanced kidney injury in cirrhosis. Furthermore, the clear dose–response relationship across AKI severity categories and the consistency of findings across multiple sensitivity analyses—including exclusion of comorbidities, CKD, and sepsis—strengthen the validity and generalizability of our results and reduce the likelihood that findings are driven by residual confounding or model specification.
Beyond its impact on mortality, AKI was associated with substantial increases in healthcare utilization. Patients with AKI experienced significantly longer hospitalizations and higher costs, with dialysis-requiring AKI associated with nearly a threefold increase in length of stay and a more than threefold increase in hospital costs. These findings highlight AKI as a major driver of inpatient resource utilization in cirrhosis. The magnitude of these effects suggests that AKI is associated not only with clinical deterioration but also with substantial strain on healthcare systems. Given the high prevalence of cirrhosis-related hospitalizations, even modest reductions in AKI incidence or severity may translate into meaningful improvements in healthcare efficiency and cost containment. These findings position AKI as a key target for interventions aimed at improving both clinical outcomes and healthcare resource utilization.
An important novel finding of this study is the presence of significant heterogeneity in the association between AKI and mortality across patient subgroups. The relative impact of AKI was attenuated among patients with underlying CKD compared with those without CKD, suggesting that AKI may represent a greater relative physiological insult in patients with lower baseline renal dysfunction. This finding is consistent with our sensitivity analyses, in which exclusion of CKD resulted in higher effect estimates, further supporting this interpretation. Similarly, the association between AKI and mortality was stronger among younger patients, which may reflect differences in baseline risk. Although older patients had higher absolute mortality, younger patients generally have lower baseline mortality risk; therefore, the development of AKI may represent a more substantial relative increase in risk in this population. In contrast, older patients often have multiple competing risks of mortality, which may attenuate the relative impact of AKI. This interpretation is consistent with prior studies demonstrating that the association between AKI and mortality does not increase proportionally with age, suggesting that the relative effect of AKI may be attenuated in older populations [22].
Interestingly, several comorbidities, including diabetes, hypertension, and chronic kidney disease, were associated with lower in-hospital mortality in adjusted analyses. While this finding may appear counterintuitive, it is well described in studies using administrative datasets and likely reflects a combination of residual confounding, coding practices, and differences in disease ascertainment [23, 24]. Patients with documented chronic conditions may have more complete coding and greater representation of comorbidity burden, whereas patients without coded comorbidities may include individuals with underdiagnosed conditions or more acute, severe presentations. Additionally, coding of chronic conditions may be more complete among survivors, introducing ascertainment bias. Importantly, sensitivity analyses excluding comorbidities demonstrated similar effect estimates for AKI, suggesting that the primary association between AKI and mortality is robust and not driven by these factors.
The attenuated relative association between AKI and mortality among patients with CKD may reflect differences in baseline risk, healthcare engagement, and heterogeneity in the underlying spectrum of kidney injury [25]. Patients with established CKD often have more frequent healthcare contact and closer monitoring, which may facilitate earlier recognition and management of kidney-related complications. Prior studies have shown that early nephrology follow-up after AKI is associated with improved survival, supporting the potential role of care processes in modifying outcomes [26].
In the context of cirrhosis, these findings may also reflect the dominant role of liver disease severity and acute decompensation in determining outcomes. Patients without documented comorbidities may represent a subgroup with more advanced or acutely decompensated cirrhosis, in whom traditional comorbid conditions play a less prominent role in risk stratification. In this setting, the development of AKI, particularly in patients without pre-existing CKD, may reflect a more acute and severe deviation from baseline physiological status, such as that seen with sepsis or other forms of circulatory dysfunction, and may therefore be associated with a greater relative increase in mortality risk. Kidney injury may exist along a continuum that is not fully captured by administrative definitions. A recent meta-analysis demonstrated increased mortality even among patients with acute kidney disease without prior overt AKI, highlighting that clinically significant renal dysfunction may not be fully captured by administrative or creatinine-based definitions [27]. In this context, differences in the underlying spectrum of kidney injury may contribute to the observed heterogeneity in outcomes across patient subgroups in our study.
From a clinical and policy perspective, our findings emphasize the importance of early recognition and prevention of AKI in patients with cirrhosis. Strategies such as careful volume management, avoidance of nephrotoxic medications (e.g., nonsteroidal anti-inflammatory drugs and contrast agents), and early identification of high-risk patients may help mitigate the development and progression of AKI. The strong graded association between AKI severity and outcomes suggests that AKI staging could be incorporated into clinical risk stratification tools to guide management decisions. At the health system level, targeted interventions aimed at reducing AKI incidence may represent an important opportunity to improve outcomes while reducing costs. In addition, implementation of standardized AKI prevention protocols and early specialty consultation may further improve outcomes. Future studies should evaluate whether targeted AKI prevention strategies can reduce morbidity and healthcare costs in this population.
This study has several important strengths. It utilizes a large, nationally representative dataset, allowing for broad generalizability of findings across the United States. The inclusion of detailed demographic, socioeconomic, and clinical variables enabled comprehensive adjustment for potential confounders. Additionally, the consistency of findings across multiple sensitivity and interaction analyses supports the robustness and internal validity of the results.
However, several limitations should be acknowledged. As an administrative database study, identification of acute kidney injury (AKI) relied on ICD-10-CM codes, which may be subject to misclassification and do not allow application of laboratory-based definitions such as KDIGO criteria. Consequently, we were unable to assess AKI severity using standardized creatinine-based staging. Instead, AKI severity was categorized based on dialysis requirement, which may be influenced by clinical decision-making, patient eligibility, and goals of care. As a result, some patients with severe AKI who were not candidates for dialysis may have been misclassified, and the dataset does not capture the clinical criteria underlying dialysis initiation.
In addition, the Nationwide Inpatient Sample does not provide information on the timing of AKI onset, precluding distinction between AKI present on admission and hospital-acquired AKI, and limiting the ability to establish temporal relationships between AKI and clinical outcomes. The dataset also lacks granular clinical data, including laboratory values required to calculate measures of liver disease severity such as the Model for End-Stage Liver Disease (MELD) score or Child–Pugh classification, which may result in residual confounding related to underlying liver disease severity. Finally, residual confounding may persist despite adjustment, and the observational design precludes causal inference.
Conclusion
In summary, acute kidney injury is a common and clinically significant complication among patients hospitalized with cirrhosis and is strongly associated with increased mortality and healthcare utilization. We observed a clear graded relationship between AKI severity and adverse outcomes, along with significant heterogeneity across patient subgroups. Notably, the relative impact of AKI varied by age and chronic kidney disease status, underscoring the importance of considering baseline patient characteristics when interpreting risk.
These findings highlight the need for improved risk stratification and early identification of patients at highest risk for AKI-related complications. Future studies should focus on refining prediction models and evaluating targeted prevention and management strategies tailored to specific patient populations. Efforts to enhance early recognition and management of AKI may represent an important opportunity to improve outcomes while reducing healthcare burden in patients with cirrhosis.
Supplementary Information
Below is the link to the electronic supplementary material.
Acknowledgements
We wanted to acknowledge all the HCUP Data Partners that contribute to HCUP. A link to the HCUP-US web page that contains the list of State organizations is here. (https://hcup-us.ahrq.gov/db/hcupdatapartners.jsp). We also wish to thank Dr. Yu-Jun Chang and Dr. Xun Guo Huang for assistance with data analysis.
Author contributions
BT and CO conceived of the presented idea. BT implemented, collected, analyzed, and interpreted the data. CO conducted literature reviews. AR supervised the project, provided insights, and assisted with revisions. All authors discussed the results and contributed to the final manuscript.
Funding
The authors declare that they received no funding.
Data availability
The data that support the findings of this study are available from the Agency for Healthcare Research and Quality, Department of Health and Human Services of the United States. However, restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the author upon reasonable request and with permission of the Agency for Healthcare Research and Quality.
Declarations
Ethics approval and consent to participate
BayCare Health System Institutional Review Board (IRB) Office assessed that the proposed activity does not constitute research involving human subjects as defined by DHHS and FDA regulations. IRB review and approval of this project is not required (Inquiry determination dated October 22, 2025). The analysis used fully de-identified data from the Healthcare Cost and Utilization Project (HCUP) National Inpatient Sample, and no identifiable private information or intervention involving human participants occurred. All study procedures were conducted in accordance with the ethical principles of the Declaration of Helsinki. Because no human subjects were involved, informed consent was not required per principal.
Consent for publication
Not applicable.
AI assistance
During the preparation of this work, Large Language Models (LLMs) were not used. The authors reviewed and revised the material and took full responsibility for the content.
Competing interests
The authors declare no competing interests.
Footnotes
Study Design/Description:
This study evaluated how acute kidney injury (AKI) affects outcomes among hospitalized patients with cirrhosis using data from the 2023 Nationwide Inpatient Sample, a large, nationally representative database of U.S. hospitalizations. We included adult patients with cirrhosis and identified those who developed AKI, including a subgroup with severe AKI requiring dialysis. We then compared outcomes between patients with and without AKI, focusing on in-hospital mortality, length of stay, and hospitalization costs. Statistical models were used to account for differences in patient characteristics and hospital factors. Additional analyses were performed to ensure that the findings were consistent and not driven by underlying conditions such as chronic kidney disease or sepsis.
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Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The data that support the findings of this study are available from the Agency for Healthcare Research and Quality, Department of Health and Human Services of the United States. However, restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the author upon reasonable request and with permission of the Agency for Healthcare Research and Quality.