Acute Kidney Injury Following Adult Lung Transplantation
Acute kidney injury (AKI) is a significant and common complication following lung transplantation (LTx), associated with high morbidity and mortality. This retrospective study aimed to assess the incidence of AKI after LTx, analyze associated perioperative factors, and evaluate clinical outcomes in adult LTx recipients at the China-Japan Friendship Hospital in Beijing between March 2017 and December 2019. The study included 191 patients, focusing on AKI incidence, risk factors, mortality, and kidney recovery. The findings highlight the complexity of AKI pathogenesis, the importance of prerenal causes, and the adverse impact of persistent and severe AKI on patient outcomes.
Introduction
AKI is a major cause of perioperative morbidity and mortality following LTx. The incidence of AKI ranges between 39% and 69%, with associated mortality rates of 16% to 50%. Approximately 5% to 13% of patients require renal replacement therapy (RRT) after AKI. Despite advancements in surgical techniques, LTx remains a high-risk procedure, often complicated by hemodynamic instability and nephrotoxic drug exposure, which are critical risk factors for AKI. This study sought to provide a comprehensive analysis of AKI incidence, risk factors, and outcomes in a single-center cohort of LTx recipients.
Methods
The study was approved by the Ethics Committee of the China-Japan Friendship Hospital, and written informed consent was obtained from all participants. The retrospective cohort included adult patients aged 18 to 65 years who underwent LTx (single or double) between March 2017 and December 2019. Exclusion criteria included death within 24 hours post-LTx, pre-existing chronic kidney disease (CKD) or AKI, and unavailable vital status data.
Anesthetic and surgical management followed standard protocols at the China-Japan Friendship Hospital. Single lung transplantation (SLT) involved a posterolateral or anterolateral thoracotomy, while double lung transplantation (DLT) used the bilateral sequential LTx method. Intraoperative monitoring included invasive arterial lines, central venous catheters, and Swan–Ganz catheterization. Extracorporeal membrane oxygenation (ECMO) was selectively used for patients with severe pulmonary hypertension or right ventricular failure. RRT was initiated based on specific criteria, including urine output less than 200 mL/12 hours, blood urea nitrogen (BUN) greater than 100 mg/dL, or pulmonary edema resistant to diuretic therapy.
Immunosuppression and antibiotic protocols were standardized. Corticosteroid induction therapy was administered intraoperatively, with post-operative immunosuppression involving tacrolimus, mycophenolate mofetil, and methylprednisolone. Prophylactic antimicrobial regimens included cephalosporin, caspofungin, vancomycin, and ganciclovir, adjusted based on perioperative cultures.
AKI was defined and staged using the serum creatinine (sCr) criteria from the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. AKI was defined as an increase in sCr by 26.5 mmol/L or 1.5 times baseline within the first seven days post-LTx. Severity was classified into stages 1, 2, and 3, with stage 3 indicating the need for RRT. Transient AKI was defined as sCr returning below the AKI range within seven days, while persistent AKI indicated incomplete recovery or ongoing RRT.
Results
Of the 206 LTx patients, 191 were included in the analysis. The median age was 59 years, and 83% were male. The most common primary diseases were interstitial lung disease (ILD, 73%), chronic obstructive pulmonary disease (COPD, 12%), and cystic fibrosis/bronchiectasis (9%). Double LTx was performed in 46.6% of patients, and single LTx in 53.4%.
AKI occurred in 71.7% of patients within the first seven days post-LTx, with transient AKI in 22.5% and persistent AKI in 49.2%. Among AKI patients, stage 1 occurred in 14.1%, stage 2 in 24.1%, and stage 3 in 33.5%. RRT was required in 18.3% of AKI patients.
Risk factors for AKI included male sex, older age, pre-operative mechanical ventilation (MV), intraoperative or post-operative severe hypotension, post-operative lactate greater than 3 mmol/L, septic shock, multiple organ dysfunction (MODS), reintubation, prolonged MV or ECMO, higher tacrolimus trough levels, and the use of nephrotoxic agents. Persistent AKI was independently associated with pre-operative pulmonary hypertension, severe hypotension, post-operative MODS, higher tacrolimus levels, and nephrotoxic drug use.
Patients with AKI had longer durations of post-operative MV and ICU stays compared to those without AKI. Persistent AKI was associated with more severe kidney injury, longer MV duration, longer ICU stays, and worse kidney function at one year post-LTx. The 30-day and 1-year survival rates were significantly lower in persistent AKI patients compared to those with transient AKI or no AKI. The 1-year survival rate decreased with worsening AKI severity, from 93% in patients with no AKI to 47% in those with stage 3 AKI.
Discussion
AKI is a common and serious complication following LTx, with a complex pathogenesis influenced by prerenal factors. The study findings underscore the importance of optimizing hemodynamic management, judicious use of vasoactive agents, and minimizing nephrotoxic drug exposure to prevent AKI. Persistent and severe AKI were associated with poor short- and long-term outcomes, including prolonged MV, extended ICU stays, worse kidney function, and reduced survival.
The study’s limitations include its retrospective design, single-center focus, and small sample size, which may limit the generalizability of the results. Additionally, the exclusion of urine output data from the KDIGO classification may have affected the AKI assessment. Future studies should explore the impact of fluid homeostasis on kidney function and survival post-LTx.
Conclusions
AKI is a prevalent complication following LTx, with significant implications for patient outcomes. The study highlights the critical role of prerenal factors in AKI development and the adverse effects of persistent and severe AKI on kidney function and survival. Preventive strategies, including optimizing hemodynamics and minimizing nephrotoxic drug exposure, are essential to improve outcomes in LTx recipients. The findings emphasize the need for further research to better understand and mitigate the risk of AKI in this vulnerable population.
doi.org/10.1097/CM9.0000000000001636
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