Objectives: Acute kidney injury is a frequent complication after liver transplant and is associated with adverse patient and graft outcomes. This study aimed to identify preoperative, perioperative, and postoperative risk factors for early postoperative acute kidney injury in patients undergoing liver transplant for chronic liver disease.
Materials and Methods: This retrospective, single-center cohort study included adult patients (≥18 years) who underwent liver transplant between April 1998 and April 2023 at Baskent University Ankara Hospital. Patients having pretransplant end-stage renal disease and with less than 1 year of posttransplant follow-up were excluded. Acute kidney injury was defined according to the Kidney Disease: Improving Global Outcomes 2012 criteria. Pretransplant and posttransplant demographic, clinical, and laboratory data were analyzed.
Results: The study included 179 patients followed for 120 ± 76 months (mean age, 43 ± 14 years; 72% male). Early postoperative acute kidney injury occurred in 103 patients (57.5%). Patients with acute kidney injury had higher preoperative Child-Pugh and Model for End-Stage Liver Disease-Sodium (MELD-Na) scores (both P < .⁰⁰¹), a greater prevalence of ascites (P = .⁰⁰³) and hepatorenal syndrome (P = .⁰⁰⁷), and higher baseline serum creatinine levels (P < .⁰⁰¹). Early postoperative infections (P < .⁰⁰¹) and surgical complications (P = .⁰⁰³) were also more frequent in the acute kidney injury group. In multivariate analysis, preoperative ascites, higher Model for End-Stage Liver Disease-Sodium scores, and lower preoperative low-density lipoprotein cholesterol levels were independently associated with early postoperative acute kidney injury.
Conclusions: The severity of underlying liver disease is the main determinant of early postoperative acute kidney injury after liver transplant. Optimization of reversible etiologic factors and careful perioperative hemodynamic management may reduce the risk.

Key words : End-stage liver disease, Liver transplantation, Postoperative complications, Risk factors

Introduction
Liver transplant (LT) is the standard treatment for patients with end-stage liver disease and results in substantial improvements in survival and functional status. However, despite major advances in surgical techniques, perioperative management, and immunosuppression strategies, acute kidney injury (AKI) remains one of the most frequent and clinically significant early postoperative complications, owing to its high prevalence and strong association with adverse short-term and long-term outcomes.¹ Previous studies have reported that AKI occurs in more than 50% of LT recipients.² The reported incidence varies widely, largely due to differences in AKI definitions, perioperative management strategies, and baseline patient characteristics.^3,4 In a large meta-analysis published in 2017, the incidence of postoperative AKI was reported to be as high as 70%.⁵ Importantly, posttransplant AKI is associated with an increased need for renal replacement therapy, greater susceptibility to infections, prolonged intensive care unit and hospital stays, and increased mortality.⁶ The pathophysiology of AKI after LT is multifactorial and involves preoperative factors such as advanced age, comorbidities, severity of liver disease, and pretransplant renal dysfunction; intraoperative factors including hemodynamic instability and ischemia-reperfusion injury; and postoperative contributors such as early allograft dysfunction, surgical complications, and exposure to nephrotoxic immunosuppressive agents.^5,7-10 Together, these overlapping mechanisms underscore the importance of early risk stratification and meticulous perioperative management to mitigate the risk of posttransplant AKI. Although AKI after LT has been extensively investigated, much of the existing literature is limited by small sample sizes, heterogeneous patient populations, or relatively short follow-up periods.² To address these limitations, the present study evaluated postoperative AKI in a large, single-center cohort over an extended study period. The objectives were to determine the incidence of AKI after LT, identify relevant preoperative and perioperative risk factors, and assess its clinical effect in the early posttransplant period.

Materials and Methods
This study was conducted in accordance with the Declaration of Helsinki and approved by the Baskent University Medical and Health Sciences Research Board (project No. KA23/237; July 25, 2023). The requirement for informed consent was waived due to the retrospective design. In this retrospective cohort study, we evaluated adult patients (≥18 years) who underwent LT for chronic liver disease between April 1998 and April 2023 at Baskent University Ankara Hospital. We excluded patients with end-stage renal disease at the time of transplant or with less than 1 year of posttransplant follow-up. We collected demographic characteristics, comorbidities, alcohol use, liver disease etiology, and cirrhosis-related complications. Transplant-related variables included donor type (living or deceased), retransplant status, and cold ischemia time. Early postoperative clinical variables included surgical and vascular complications, transfusion requirements, early allograft dysfunction, acute rejection episodes, need for plasmapheresis, infections, and length of stay in hospital. Renal function was assessed using serum creatinine levels and estimated glomerular filtration rate (eGFR), which were measured at regular intervals during the first postoperative year and annually thereafter for up to 10 years following transplant. The eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation (known as the CKD-EPI equation).¹¹ Acute kidney injury and chronic kidney disease (CKD) were defined according to the Kidney Disease: Improving Global Outcomes 2012 criteria.^12,13 Acute kidney injury was defined based on changes in serum creatinine and/or urine output, with early postoperative AKI referring to episodes occurring during the index hospitalization after LT. Chronic kidney disease was defined as abnormalities of kidney structure or function, persisting for at least 3 months, with postoperative CKD referring to an eGFR <60 mL/min/1.73 m² for ≥3 months at any point during follow-up after LT. Patients with a pretransplant eGFR <90 mL/min/1.73 m² were classified as having preoperative CKD. Because only 4 patients had a pretransplant eGFR <60 mL/min/1.73 m², this higher threshold was chosen to allow meaningful statistical analysis. The primary outcome was the development of early postoperative AKI. We obtained pretransplant and postoperative laboratory parameters, including renal function tests, electrolyte measurements, liver biochemistry, lipid profile, inflammatory markers, complete blood count, coagulation profile, and urine protein measurements, from electronic medical records. We used SPSS software version 25.0 (IBM) for all statistical analyses. We expressed continuous variables as mean ± SD or median values (with interquartile range [IQR]) and categorical variables as frequencies (with percentages). We performed group comparisons with appropriate parametric or nonparametric tests for continuous variables and the χ2 or Fisher exact test for categorical variables. We conducted multivariate logistic regression analyses to identify independent predictors of early postoperative AKI. P < .⁰⁵ was considered statistically significant.

Results
During the study period, 188 orthotopic LTs were performed in adult recipients. Six patients who underwent transplant for indications other than chronic liver disease were excluded (familial hypercholesterolemia, n = 2; type 1 glycogen storage disease, n = 1; acute liver failure, n = 2; pancreatic neuroendocrine tumor with liver metastasis, n = 1). One patient with oxalosis who underwent simultaneous liver-kidney transplant was excluded due to early chronic graft rejection, and 2 patients with end-stage renal disease at the time of transplant were also excluded. The final cohort comprised 179 adult LT recipients (mean age, 43 ± 14 years; 72% male) with a mean posttransplant follow-up of 120 ± 76 months. At transplant, 14.5% of patients were classified as Child-Pugh class A (score of 5-6), 37.4% as Child-Pugh class B (score of 7-9), and 48.0% as Child-Pugh class C (score of 10-15). Most transplants were performed using living donor grafts (68.2%); among deceased donor recipients, the mean cold ischemia time was 8.5 ± 3.4 hours. Primary transplant was performed in 96.1% of patients, whereas 3.9% underwent retransplant. Baseline demographic and clinical characteristics are presented in Table 1. All patients received triple immunosuppression with a CNI (tacrolimus or cyclosporine), prednisolone (discontinued after 3 months), and mycophenolate mofetil. Mechanistic target of rapamycin (mTOR) inhibitors were used in 66 patients (Table 1). Early postoperative AKI occurred in 103 patients (57.5%). Patients with AKI had more advanced liver disease, with a higher proportion classified as Child-Pugh C compared with those without AKI (62% vs 29%; P < .⁰⁰¹). Liver disease etiology differed between groups (P = .⁰⁴⁴), with alcohol-related and autoimmune liver disease more common among patients who developed AKI. Recipient age, sex, preoperative comorbidities (diabetes mellitus and hypertension), cold ischemia time, and intraoperative red blood cell transfusion volume did not differ between groups. Factors associated with early postoperative AKI are summarized in Table 2. Preoperative CKD (eGFR <90 mL/min/1.73 m²) was present in 16 patients (8.9%). Compared with patients without CKD, those with preoperative CKD had higher rates of preoperative hypertension (37.5% vs 6.8%), hepatorenal syndrome (31.3% vs 7.4%), preoperative AKI (31.3% vs 11.0%), and early postoperative AKI (93.8% vs 54.0%) (all P < .⁰⁵). Patients who developed postoperative AKI had a significantly longer hospital stay than those without AKI (median, 24 vs 15 days; P < .⁰⁰¹). Preoperative and postoperative laboratory parameters in LT recipients according to early postoperative AKI status are summarized in Table 3. In multivariate logistic regression analysis, the presence of ascites (odds ratio 3.80; 95% CI, 1.03-14.04; P = .⁰⁴⁵), higher score for the Model for End-Stage Liver Disease-Sodium (MELD-Na) (odds ratio 1.32; 95% CI, 1.14-1.53; P < .⁰⁰¹), and lower preoperative low-density lipoprotein (LDL) cholesterol levels (odds ratio 0.98; 95% CI, 0.96-0.99; P = .⁰¹²) were identified as independent risk factors for early postoperative AKI. Preoperative prothrombin time showed a trend toward significance but was not significant in the multivariate model (odds ratio 0.84; 95% CI, 0.69-1.02; P = .⁰⁷⁸).

Discussion
In this retrospective single-center observational cohort study, we evaluated risk factors for early postoperative AKI after LT. Early postoperative AKI occurred in 57.5% of recipients, confirming its high incidence and clinical relevance, consistent with previous reports.^2,14 The risk of postoperative AKI increased with progression to decompensated cirrhosis; higher MELD-Na scores, ascites, and lower preoperative LDL cholesterol levels were identified as independent predictors of early postoperative AKI. Previous studies have identified preoperative renal dysfunction as a predictor of post-LT AKI.^2,15,16 In our cohort, postoperative AKI was more frequent in patients with preoperative CKD and was associated with higher baseline serum creatinine; however, preoperative CKD was not an independent predictor in multivariate analysis, likely due to the small sample size. The higher prevalence of ascites, hepatorenal syndrome, and preoperative AKI in patients with preoperative CKD suggests that preoperative CKD reflects greater liver disease severity and contributes to the development of postoperative AKI. Patients with decompensated cirrhosis are highly susceptible to perioperative renal ischemia after LT due to profound systemic and renal vasoconstriction and circulatory dysfunction.¹⁷ In agreement with previous studies, higher MELD-Na and Child-Pugh scores were strongly associated with postoperative AKI, which was also linked to prolonged hospital stay.^3,18,19 Ascites and hepatorenal syndrome, both of which are key manifestations of advanced portal hypertension and impaired effective arterial blood volume, were more prevalent among patients who developed AKI, and preoperative ascites emerged as an independent predictor. In chronic liver failure, impaired hepatic synthetic function results in reduced serum cholesterol and albumin levels. Previous studies have shown an inverse relationship between LDL cholesterol and MELD scores and have identified hypoalbuminemia as a risk factor for postoperative AKI.²⁰ Consistent with these findings, lower preoperative LDL cholesterol predicted early postoperative AKI in our cohort, whereas albumin levels were significantly lower in patients who developed AKI, reflecting more advanced hepatic dysfunction. In addition, patients with postoperative AKI had lower preoperative platelet counts, likely related to cirrhosis-associated hypersplenism and circulatory dysfunction, in agreement with the findings of Park and colleagues from 2021, who reported thrombocytopenia as an independent predictor of early postoperative AKI.²¹ In our study, alcohol-associated liver disease and a history of alcohol use were associated with a higher incidence of postoperative AKI. Alcohol is known to accelerate the progression of chronic liver disease through synergistic interactions with other hepatic insults, thereby increasing susceptibility to postoperative renal dysfunction.²² In 2024, Ma and colleagues reported severe AKI, higher requirements for renal replacement therapy, and increased short-term mortality in patients with alcohol-associated hepatitis,²³ and their results support our findings. In our cohort, surgical complications were associated with a higher risk of early postoperative AKI, consistent with previous reports.²⁴ In contrast, cold ischemia time and intraoperative transfusion volume were not significantly related to AKI, possibly reflecting standardized surgical techniques and contemporary perioperative management at our center. Early postoperative plasmapheresis was more common among patients who developed AKI, likely reflecting greater disease severity, allograft dysfunction, and perioperative hemodynamic instability rather than a direct nephrotoxic effect. In our cohort, early postoperative infections and exposure to nephrotoxic antibiotics were associated with a higher incidence of postoperative AKI, supporting the role of infection-related systemic inflammation in precipitating renal dysfunction, as evidenced by higher postoperative C-reactive protein levels. Consistent with this observation, Cabezuelo and colleagues identified bacterial infection as a risk factor for postoperative AKI after LT.¹⁵ In addition, lower postoperative leukocyte and neutrophil counts in patients with AKI may reflect severe systemic inflammation, infection-related bone marrow suppression, or intensified immunosuppression. In our cohort, immunosuppression regimens differed according to early postoperative AKI status, with less frequent tacrolimus use and more frequent cyclosporine or mTOR inhibitor use among patients with AKI, likely reflecting efforts to reduce calcineurin inhibitor (CNI) exposure. Calcineurin inhibitor-related AKI is primarily mediated by renal arteriolar vasoconstriction and thrombotic microangiopathy, leading to reduced renal perfusion.⁴ Although CNI minimization has been proposed as a renal-sparing strategy, its protective benefit remains inconsistent across studies.^5,25 These findings highlight the importance of careful selection and close monitoring of immunosuppression therapy in high-risk patients. The retrospective single-center design of our study and the lack of detailed urinary parameters limited comprehensive renal assessment, and short-term postoperative mortality was not evaluated. Despite these limitations, the study benefits from a large cohort for a longer timeframe (25 years). Further multicenter, prospective studies are warranted to better define risk profiles and clinical outcomes of AKI after LT. Overall, the severity of underlying liver disease appears to be a key determinant of early postoperative AKI. Optimization of reversible disease-related factors (eg, alcohol use, uncontrolled viral hepatitis, cirrhosis-related complications), careful perioperative management, and close postoperative renal monitoring may help reduce the risk of early AKI after LT.