Simultaneous Liver and Kidney Transplant in a Middle-Income Country: A Single-Center Experience

Introduction

Liver-kidney transplantation (SLKT) is a challenging surgical procedure that is the preferred treatment option for patients with advanced failure of both organs. It serves as an alternative to optimize patient survival, particularly in cases where there is no expectation of renal function improvement after an isolated liver transplant [1]. This procedure has several advantages, including improved liver graft survival, reduced post-transplant dialysis-related survival issues [2], and important immunological benefits [3], making it a suitable alternative for certain patients.

The first successful SLKT was reported in 1984 by Margreiter et al [4]. Since the Model for End-Stage Liver Disease (MELD) scoring system was implemented in 2002, many countries around the world have reported an increase in the number of SLKTs performed [5]. However, there are no standardized eligibility criteria for SLK worldwide, and each country has its own allocation policy. SLKT currently accounts for up to 8.4% of all liver transplants in the United States and is routinely performed at many transplant centers worldwide with favorable outcomes [5,6].

These encouraging statistics could hardly be transferred to other countries facing suboptimal and marginal conditions [7]. SLKT entails a significant challenge due to the management of multiple factors that play a determinant role in its success. Patients are often severely compromised and require careful management by a multidisciplinary team of surgeons, anesthesiologists, hepatologists, and nephrologists [8]. Simultaneous transplantation increases surgical times considerably, so adequate logistics are necessary due to the different tolerances of the organs to cold ischemia. All these factors can be difficult to provide in low- and middle-income countries where human and technical resources are scarce.

Data on SLKT management and outcomes has been obtained mostly from large centers in the United States, and limited data have been sourced from other industrialized countries [9–11]. In contrast, in Latin American countries, SLKT is still uncommon, and there is a limited literature on its outcomes. [12,13]. In Colombia, according to the annual report of the Organ Donation and Transplant Network of the National Health Institute, 293 liver transplants were performed in 2023. Of these, 14 were SLKT, corresponding to 4.5% [7]. This study aimed to describe the experience with SLKT in a high-complexity center in Colombia trying to determine if the outcomes could be comparable to those found in the current literature.

Material and Methods

The institutional review boards (research and ethics) approved the study, and because of its nature waived the need for individual informed consent. We included all adult and pediatric patients who underwent SKLT between January 2005 and December 2023 at Fundación Cardioinfantil-Instituto de Cardiología in Bogotá, Colombia. Patients who received additional organ transplants or underwent re-transplantation were excluded. Given the limited number of cases, both pediatric and adult patients were included to provide a broader perspective of the procedure in our setting. During the study period, anesthetic and surgical techniques were applied following established institutional protocols, although these protocols have been modified over the years.

Data were collected from departmental databases and both physical and electronic medical records. Preoperative variables included demographic information (gender, age, body mass index), comorbidities, MELD score, etiology of liver and kidney dysfunction, dialysis status, and laboratory values (international normalized ratio [INR], albumin, creatinine, hemoglobin, platelets, bilirubin). Intraoperative data included operative times, duration of cold ischemia, monitoring used, administration of vasopressors and inotropes, fluid balance, estimated blood loss, and blood transfusion. Postoperative information involved immunosuppression, administration of vasopressor and inotropic agents, transfusions, days to extubation, intensive care unit (ICU) and hospital length of stay, reoperations, and post operative complications (atrial fibrillation, seizures, infections). Graft-related complications were defined as graft dysfunction, including vascular thrombosis, rejection episodes, and primary non-function, as documented in medical records. These events were identified through clinical assessments, imaging studies, and laboratory findings during hospitalization and follow-up visits.

Continuous variables were summarized as mean±standard deviation or median with interquartile range, depending on data distribution assessed using the Shapiro-Wilk test. Categorical variables were reported as absolute and relative frequencies. Survival was estimated using the Kaplan-Meier method and presented descriptively. For survival analysis, death was considered the event, and patients were censored at their last follow-up. Follow-up extended from the date of surgery to the patient’s most recent visit to the institution in 2024. Mortality data were verified using medical records and the National Civil Registry database. No statistical comparisons or inferential analyses were performed. All statistical analyses were conducted using GraphPad Prism 8.4.3 (GraphPad Software, San Diego, Calif, United States).

Results

Over the course of the 18-year study period, a total of 939 isolated liver transplants and 674 isolated kidney transplants were performed at our institution. From January 2005 to December 2023, 41 patients underwent SLKTs, representing 4.18% of liver transplants and 5.73% of kidney transplants. In our institution, the first SLKT was performed in 2007, and its frequency increased steadily over the years, ranging from one to 6 procedures per year. However, there was a decrease in the number of procedures performed in 2020 due to the impact of the COVID-19 pandemic, as shown in Figure 1.

Baseline demographics are presented in Table 1.The major indications for liver transplantation differed by age group, with alcoholic cirrhosis (38.7%) being more common in adults and congenital liver fibrosis (50%) in pediatric patients. Pediatric patients also exhibited rare hepatic conditions such as glycogenosis type IV, Alagille syndrome, and Caroli syndrome. Meanwhile, adults showed a variety of less common conditions like hepatitis C, Budd-Chiari syndrome, and hemochromatosis. Renal conditions varied significantly between age groups. In adults, diabetic nephropathy was the most common (48.3%), whereas children were more frequently affected by nephronophthisis and polycystic kidney disease (30% each). Additional rare renal conditions included tubulointerstitial nephritis and type I hyperoxaluria in children, hepatorenal syndrome type I, and NSAID nephropathy in adults. A glomerular filtration rate (GFR) of less than 30 mL/min was observed in 38 patients. The remaining 3 patients had GFR corresponding to KDIGO stages IIIa and IIIb (Table 1).

Table 2 presents the intraoperative parameters, including fluid management and surgical times. Both groups required a significant blood transfusion during the procedure: 26 (84%) of the adult patients and all of the pediatric patients received packed red blood cells, followed by fresh frozen plasma in 15 (48%) of the adult patients and 7 (70%) of the pediatric patients. All adults and half of the pediatric patients received grafts from deceased donors. The remaining 50% of the children received grafts from living donors. Intraoperative dialysis was not required for any patient.

All patients were admitted to the ICU following surgery for immediate follow-up care. Noradrenaline was the most used vasopressor, administered to 67% of adults and 40% of children. In the pediatric population, the need for inotropic support was higher, with 70% of patients requiring it. Milrinone was the most used agent, administered in 71% of pediatric cases. By contrast, only 13% of adult patients required inotropic support. Postoperative transfusions were administered to 30% of the pediatric population and 55% of the adults. Immunosuppressive therapy was more commonly initiated in pediatric and adult patients with Basiliximab, with 100% and 74% of cases, respectively. The remaining patients received induction with daclizumab and methylprednisolone (Table 2).

Postoperative renal replacement therapy was administered to 30% (n=3) of pediatric patients and 12.9% (n=4) of adult patients. Infection occurred in 90% (n=9) of the pediatric group, with urinary tract infection (UTI) (n=4) as the most common cause. In the adult group, 35.5% (n=11) experienced complications due to infection, with bacteriemia (n=5) as the most common presentation. No cases of acute rejection and only 1 case of graft failure was reported in the adult group. Four adult patients and 2 pediatric patients experienced bleeding, contributing to the death of one adult. Despite having functional grafts, 2 adults and 2 children died in the first days postoperatively due to sepsis and multiple organ failure. The pediatric group exhibited a longer ICU and hospital length of stay.

Our study reports overall survival rates at 1, 3-, 5-, 10-, and 15-year post-surgery as 92.6%, 80.4%, 75.6%, 73.1%, and 73.1%, respectively (Figure 2). Follow-up was conducted from the surgery date until the last available visit up to 2024.

Discussion

There is growing interest within the medical community in the clinical significance of SLKT compared to separate liver and kidney transplantation. This interest has been particularly pronounced since the MELD scoring system was introduced for organ allocation in 2002. Since then, SLKT has increased significantly, becoming one of the most common combined organ transplant procedures [5].

In our institution, 41 SLKTs were performed over 18 years. This represents 4.18% of liver transplants and 5.73% of kidney transplants performed during this period. This proportionally low number of SLKT aligns with trends observed in other Latin American centers, where the procedure remains relatively uncommon. For instance, Mexico reported 13 SLKT cases between 2007 and 2020, while a single center in Brazil conducted 16 combined liver-kidney transplants, accounting for 2.7% of kidney transplants and 2.5% of liver transplants over 10 years [12]. The limited number and small growth of SLKT in these countries could be explained by the use of systems based on geographic, logistical and technical criteria for the distribution and allocation of grafts. The systems consider recipient lists at national or regional level, and only a few centers are equipped to perform such interventions. One of the main challenges is the shortage of donors, primarily due to lack of awareness about brain death and the benefits of organ donation, as well as economic constraints, inadequate hospital infrastructure, and disparities in access to transplantation. Addressing these issues requires enhanced public education, reducing family refusal rates, expanding infrastructure, ensuring equitable access, improving organ viability, optimizing logistics, and refining preservation techniques [14–16].

Our population shares similar characteristics to those found in previous series. In pediatric patients the most common indication for SLKT was polycystic kidney disease associated with congenital hepatic fibrosis, followed by nephronophthisis (30% each) [17,18]. In adults, alcoholic cirrhosis was the leading cause of hepatic disease (38.7%), while viral hepatitis was more prevalent in other countries, and diabetic nephropathy was the most common renal condition (48.3%, aligning with data from previous studies). As for the MELD score, our study showed a lower average compared to other regions. For instance, Veras et al and Kim et al reported averages of 23.6±3.67 and 30.1±8.2, respectively, while Korayem et al scored 36, reflecting a higher severity of liver disease in those areas [12,19,20].

There is no global consensus on the indication of combined organ transplantation, as it should be individualized based on various clinical, anatomical, and histological factors. At our institution, combined transplantation is performed in patients requiring liver transplantation who also have renal disease, under the following conditions: patients on dialysis for more than 4 weeks; pre-dialysis patients with a GFR less than 30 ml/min; pre-dialysis patients with a GFR less than 35 ml/min and an associated sign of renal damage, such as proteinuria; or pre-dialysis patients with a renal biopsy showing more than 20% glomerulosclerosis.

The optimization of perioperative management including logistic and surgical technique are crucial to ensure graft and patient survival. Specifically, variations in ischemia times may impact graft function and postoperative outcomes. The duration of our SLKT (531.8±100.8 minutes) correlates with the ranges reported in the literature [21,22], In terms of cold ischemia times for the liver graft, our results (388.9±121.6 minutes) are comparable to those reported by Koscielska et al [22] and Rajakumar et al [21]. For the kidney, our cold ischemia times (586.3±149 minutes) are similar to the 583 minutes reported for deceased kidney donors [21].

The demand for blood product transfusions arises from significant intraoperative blood loss and preexisting coagulopathies in these patients. In our series, 84% of adults and 100% of pediatric patients received red blood cell transfusions; plasma transfusions were administered to 48% of adults and 70% of children. Platelets and cryoprecipitate were also administered, although in smaller proportions. Our institution lacks clear protocols for transfusion in SLKT, and the prescription of blood products is at the discretion of the attending anesthesiologist. This is a clear opportunity for improvement, and we are working toward the implementation of blood patient management guidelines in the perioperative setting [23].

Induction immunosuppression in kidney transplantation is strongly associated with lowering acute rejection rates within the first year. By contrast, this approach is not commonly used in liver transplantation, and there is considerable inconsistency in its use in SLKT. Kamal et al reported that induction immunosuppression did not affect patient or graft survival in SLKT. By contrast, using maintenance steroids and calcineurin inhibitors correlated with better patient and graft outcomes [24]. In the present report, 74% of adults received Basiliximab, while all children were treated with this agent, indicating a preference for its use in the pediatric population. Declizumab was limited to only 2 adults (7%). Additionally, methylprednisolone was administered to 19% of adults, with no applications in children. In our study, just one case of renal graft failure was reported in the adult group. By comparison, a Korean series identified 3 patients who experienced acute rejection of kidney allografts [20]. At the same time, a Spanish report showed no cases of acute rejection in either the kidney or the liver in their series [25]. In our study, 12.9% of adult patients required postoperative RRT, a lower rate than the 23% reported by the US multicenter SLKT Consortium [26].

An elevated rate of infections was present, particularly among the pediatric population, suggesting that these patients are particularly vulnerable to this complication. Infectious complications can lead to increased morbidity and, in some cases, fatal outcomes, as evidenced by the 2 adults and 2 children who died due to sepsis and multi-organ failure despite having functional grafts. This pattern aligns with findings from other studies: Kim et al reported 2 cases of infection-related mortality, while González et al documented 3 deaths in the immediate postoperative period—one due to sepsis from colon perforation, another from bleeding caused by a ruptured mycotic aneurysm at the arterial anastomosis, and the third from respiratory sepsis [20,25]. Some studies have indicated that the incidence of UTI in pediatric patients who have undergone isolated renal transplantation ranges from 15% to 33%. A study conducted in Germany found that 27.5% of adult and pediatric patients developed infection in the postoperative period, with this being the most prevalent complication observed [11].

The in-hospital postoperative survival rate was 90.2%. The adult group presented a higher mortality rate after discharge, with 6 additional fatal outcomes. By contrast, the pediatric group demonstrated only one additional fatal outcome. The long-term survival rates observed in our study agree with those reported in other studies. For example, our 1-year survival rate of 92.6% is comparable to series from the United States and New Zealand, where survival rates range from 94% to 92%, but slightly higher than the 90.9% reported by Kim et al. At 3 years, our survival rate of 80.4% is similar to the 81.8% in the Korean report but lower than in the US, where the three-year survival rate is 92%. Similarly, at the 5-year mark, our rate of 75.6% is lower than the 81.8% reported in Korea and the 90% in US series. Finally, our 10-year survival rates show that our 73.1% is in line with the Swiss study’s finding of 78.9% at 10 years [20,27–29].

This study had inherent limitations due to its retrospective, single-center design. Specifically, there was insufficient data regarding the dates and causes of death in patients who died in the late postoperative period after discharge. Further high-volume multicenter studies are needed to validate the results of this research.

Conclusions

In conclusion, while data on SKLT have predominantly been collected from large centers in developed countries, this study provides insights from a low-volume center in a middle-income country where information is limited. At our institution, SLKT has shown satisfactory clinical outcomes although the pediatric population appears to be at higher risk for early septic complications. The overall survival rates observed in this study suggest that this procedure is a valid option for affected patients.