Outcomes of Combined Liver-Kidney Transplantation in Polycystic Liver and Kidney Disease

Introduction

The adult polycystic liver disease (PLD) is often associated with autosomal dominant polycystic kidney disease (ADPKD), a genetic disorder with an incidence of approximately 1 in 400 to 1 in 1000 individuals [1]. ADPKD is caused by mutations in the PKD1 and PKD2 genes, located on the short arm of chromosome 16 (16p13.3-p13.12) and the long arm of chromosome 4 (4q21-q23), respectively. Approximately 78–85% of ADPKD cases are linked to PKD1 mutations, while 10–15% are attributed to PKD2 mutations, classifying them as ADPKD type 1 and type 2, respectively [1–4].

In advanced stages, adult PLD can lead to hepatomegaly, which can cause symptoms such as abdominal pain, early satiety, respiratory restriction, and difficulty with physical activity, resulting in significant malnutrition. Enlarged livers can also compress the hepatic veins, leading to outflow obstruction and related symptoms, or exert pressure on the portal vein, causing portal hypertension. In addition, hepatic cysts may spontaneously rupture or become infected, further compromising quality of life [5]. To alleviate symptoms, various treatments are available, including cyst fenestration, liver resection combined cyst fenestration, and percutaneous transhepatic drainage with sclerotherapy. However, these approaches are not suitable for all polycystic liver patients, and liver transplantation remains the only definitive treatment for those with severe complications or unsatisfactory results from other interventions.

Adult PLD patients commonly present with concomitant polycystic kidney disease, which, in its later stages, can lead to progressive renal failure and uremic symptoms such as nausea, vomiting, chest tightness, anuria, and edema, necessitating long-term dialysis or kidney transplantation. Given the high risk of organ transplant surgery and the lifelong need for immunosuppressive therapy, determining the optimal timing for transplantation remains controversial, particularly since liver function is usually preserved in these patients, and dialysis can replace kidney function temporarily. Furthermore, there is limited literature on combined liver and kidney transplantation and related immunosuppressive strategies in this patient population.

Therefore, this study retrospectively reviewed the clinical data of 8 patients with polycystic liver and kidney disease who underwent liver or combined liver and kidney transplantation at the Liver Transplantation Center of Beijing Friendship Hospital, Capital Medical University, from 2015 to 2023. The study analyzed the efficacy and strategies for organ transplantation in the treatment of APLD in light of relevant literature.

Material and Methods

From May 2015 to Jan 2024, a total of 9 patients with polycystic liver disease and polycystic kidney disease underwent organ transplantation at our center. All patients were female, with a mean age of 51.6±7.9 years (range: 40–63 years). Preoperative Model for End-Stage Liver Disease (MELD) scores averaged 20.2±7.6. All patients presented with massive hepatic enlargement, resulting in mobility impairment and severe malnutrition. Among the 9 patients, 2 received liver transplantation, while 7 underwent combined liver and kidney transplantation (CLKT) (including 2 sequential liver and kidney transplantation). Detailed demographic and clinical information of the patients is provided in Table 1.

For the CLKT procedure, liver transplantation was performed first due to the large size of the liver. A classical liver transplantation technique was employed in all 8 patients. Liver cyst fenestration was performed intraoperatively to improve visibility and minimize bleeding. After blocking the portal vein and inferior vena cava, the diseased liver was excised. Hepatic venous anastomosis was performed using 3-0 vascular sutures for the suprahepatic vena cava, 4-0 vascular sutures for the infrahepatic vena cava, and 5-0/6-0 sutures for continuous portal vein anastomosis. The arterial anastomosis was completed using 7-0/8-0 sutures. A full interrupted end-to-end biliary anastomosis was performed with 7-0 sutures. Following liver transplantation, polycystic kidneys were resected, and abdominal closure was achieved. Kidney transplantation was performed through a separate incision at the right lower abdominal oblique. The right iliac fossa was exposed in layers, and the internal and external iliac vessels were dissected. The renal vein was anastomosed to the external iliac vein using 5-0 continuous sutures for an end-to-side anastomosis, and the renal artery was anastomosed to the internal/external iliac artery using 5-0/6-0 continuous sutures for end-to-end or end-to-side anastomosis. A double-J ureteral stent was placed at the renal pelvis and the proximal ureter, followed by an anastomosis between the transplanted kidney’s ureter and the bladder mucosa using 4-0 absorbable sutures.

During surgery, patients received intravenous infusion of 20 mg of basiliximab and 10 mg/kg of methylprednisolone for induction. Postoperatively, early immunosuppressive therapy included oral tacrolimus, mycophenolate mofetil, and corticosteroids. On the fourth postoperative day, basiliximab (20 mg) was administered intravenously. Broad-spectrum antibiotics were used for 3 days for infection prophylaxis. During the first week after surgery, daily Doppler ultrasonography was performed to monitor the blood vessels of the transplanted liver, biliary tract, renal vessels, and ureters. After discharge, patients were followed regularly, and immunosuppressive therapy was adjusted according to liver and kidney function, as well as biopsy findings.

Results

PERIOPERATIVE DATA:

The mean duration of combined liver and kidney transplantation was 10.7±1.2 hours, while liver transplantation alone took an average of 5.4 hours. The average intraoperative blood loss was 975.6±555.7 mL, and the median number of blood units transfused was 5.4 (range: 0–18 units). The average postoperative hospital stay was 41.2 days (range: 13–175 days).

COMPLICATIONS:

One patient (Case 2) who underwent combined liver and kidney transplantation developed elevated transaminases 2 weeks postoperatively, suspected to be due to acute liver rejection. This was managed with high-dose methylprednisolone (500 mg daily for 3 days), after which liver function gradually returned to normal.

In Case 8, during a routine follow-up at 3 months post-surgery, a hypoechoic mass (1.6×1.9×1.4 cm) was detected in the renal sinus of the kidney graft. The mass gradually enlarged and progressed to 2 masses by 6 months postoperatively (2.2×2.0×1.7 cm, 2.2×2.2×1.6 cm), with 1 mass showing infiltrative growth. A kidney biopsy confirmed lymphocytic infiltration with partial positivity for CD20, EBER, and Ki-67 (40%), suggesting post-transplant lymphoproliferative disorder (PTLD). The immunosuppressive regimen was reduced, but 1 week later, the patient developed elevated transaminases. Liver biopsy indicated acute liver rejection (Banff score 5/9), and the immunosuppressive dose was adjusted back to its original level. Liver function gradually improved thereafter. PTLD was treated with rituximab combined with chemotherapy (R-CHOP regimen plus etoposide), resulting in remission. At 6 years after transplantation, the kidney graft developed kidney stones, which were treated successfully with percutaneous nephrolithotomy and laser lithotripsy.

Case 1 had such severe nutritional deficiencies preoperatively that she was unable to leave the bed and was confined to long-term bed rest. She underwent sequential liver and kidney transplantation. Postoperatively, she developed pneumonia caused by multidrug-resistant organisms and severe intra-abdominal infection. Despite receiving intensive combination antimicrobial therapy, including intravenous immunoglobulin, and a reduction in immunosuppressive therapy, she ultimately died of sepsis 175 days after liver transplantation (135 days after kidney transplantation)

The 8 remaining patients gradually recovered postoperatively. No major complications (Clavien-Dindo grade 2b or above) such as graft failure, bleeding, thrombosis, bile leakage, biliary stricture, urinary leakage, or ureteral obstruction intervention occurred.

RECIPIENT AND GRAFT SURVIVAL:

The total survival rate was 88.9%. The median follow-up time for the surviving patients was 45.0 months (range: 16.0 to 108.4 months), excluding the patient who died of sepsis. The 6 surviving patients who underwent combined liver and kidney transplantation had a mean preoperative eGFR of 19.8±16.4 mL/min, which increased to 64.2±12.3 mL/min at the end of follow-up.

Among the 2 patients who received liver transplantation without kidney transplantation, 1 had preserved renal function, while in the other, eGFR decreased from 45.6 mL/min preoperatively to 14.42 mL/min, and the patient is currently awaiting kidney transplantation. Three patients (Cases 7–9) who underwent liver and kidney transplantation more than 4 years ago are now maintained on tacrolimus (FK506) alone, with FK concentrations maintained at 2–6 ng/mL, and liver and kidney function remain stable.

Discussion

Reports on organ transplantation for polycystic liver disease (PLD) and polycystic kidney disease (PKD) are primarily based on single-center experiences or case reports [6–9]. In 1990, Starzl reported 4 successful organ transplantations in PLD patients, of whom 2 received liver transplantation and 2 underwent combined liver and kidney transplantation, One of the combined transplantation patients died 5 months after surgery, resulting in a 75% survival rate [10]. In 1998, Baylor University Medical Center reported 6 PLKD patients, 3 of whom received combined liver-kidney transplants and 3 underwent liver transplantation alone. Two patients died from infections postoperatively, yielding a survival rate of 66.7% [11]. The same year, Cedars-Sinai Medical Center published a report on 9 patients who received liver transplantation for PLD, with a 1-year survival rate of 89% [12]. However, with advances in surgical techniques, improvements in immunosuppressive regimens, and the widespread use of antibiotics, patient and graft survival rates have steadily increased. In 2021, Spanish researchers reported a case series of 32 PLKD patients with no perioperative mortality, and long-term follow-up revealed 2 deaths due to cardiovascular events and colon cancer [13]. A study using data from the United Network for Organ Sharing (UNOS) showed 1-, 3-, and 5-year survival rates of 91%, 90%, and 90%, respectively, for 107 PLKD patients who underwent combined liver-kidney transplantation [14]. In recent years, our center has performed organ transplantation in 9 PLD patients, with 88.9% survival rates for patients and grafts.

For asymptomatic polycystic liver disease (PLD) patients, no treatment is necessary. However, for those with symptoms due to enlarged liver volume, various treatment options can be employed to alleviate symptoms, such as percutaneous transhepatic drainage (with sclerotherapy), laparoscopic cyst fenestration, or liver resection combined with cyst fenestration [15]. The complication rate of percutaneous transhepatic drainage (with sclerotherapy) is relatively low, with severe sclerosing cholangitis-related complications occurring mainly when sclerotherapy is performed before confirming whether cysts communicate with the bile ducts [16,17]. This treatment modality is most effective for PLD patients with symptoms primarily caused by large intrahepatic cysts (diameter >10 cm). For other types of PLD, percutaneous transhepatic drainage (with sclerotherapy) may offer less symptom relief, with a higher recurrence rate [18]. In addition, repeated interventions can lead to bacterial colonization, and in the context of immunosuppression after transplantation, this increases the risk of intra-abdominal infection during the perioperative period, as well as the risk of bacteremia and sepsis. In patients whose symptoms are mainly caused by large-surface cysts, cyst fenestration can effectively alleviate symptoms [19], but recurrence remains a concern, and it may not be suitable for all PLD patients [20]. Liver resection requires careful preoperative evaluation. The selection criteria for liver resection are stricter in PLD patients, typically limited to those with Gigot type II PLD [21]. Liver resection also carries a higher risk of postoperative complications, which can increase the difficulty of subsequent liver transplantation [22]. Additionally, some non-standard liver resections, such as transverse liver resection, have been used to treat PLD, specifically the non-standard removal of liver segments III, IVB, V, and VI. This approach, which avoids disruption of the hepatic venous outflow, reduces the impact on future liver transplantation and has been adopted by some centers. However, it still carries risks such as ascites, pleural effusion, and even diaphragm injury [23,24]. When serious complications occur, such as severe malnutrition, cyst compression leading to hepatic venous outflow obstruction, portal hypertension (refractory ascites or esophagogastric variceal bleeding), or recurrent cyst infections, liver transplantation remains the only definitive cure [25].

For patients with severe symptoms of PLD, liver transplantation can significantly improve quality of life [26]. Even in advanced stages, PLD patients may maintain normal liver function, and their risk of life-threatening complications is lower compared to patients with severe liver decompensation. Given the scarcity of transplant organs, the high risks of transplant surgery, and the need for long-term immunosuppressive therapy, determining the optimal timing for liver transplantation in PLD patients is crucial, but consensus is lacking. However, our center recommends that liver transplantation should be performed as early as possible when patients develop sarcopenia, to avoid severe malnutrition, as seen in Case 1 of this study, which leads to difficulties in postoperative recovery and significantly increases the risk of infection and death.

Immunosuppressive therapy for combined liver and kidney transplant recipients generally follows the same guidelines as for liver transplant recipients. This is mainly due to the liver’s strong “immune tolerance” [27–29], which, through immune regulation, not only reduces the incidence of autologous rejection but also helps suppress kidney immune responses to some extent. This phenomenon is referred to as “cross-immune tolerance” [30]. As a result, the intensity of immunosuppressive drug use in liver-kidney transplant recipients is typically lower than in kidney transplant recipients, and lower doses of tacrolimus, mycophenolate mofetil, and steroids are used to achieve sufficient immunosuppression while minimizing adverse effects. For recipients who have undergone combined liver-kidney transplantation for more than 1 year, tacrolimus levels can be maintained at 5 ng/mL to effectively control rejection while reducing renal toxicity and the long-term risks associated with immunosuppression.

The optimal timing for liver transplantation in PLD, risk factors for complications after combined liver-kidney transplantation, and mechanisms of organ immune protection all require further clinical and basic research to improve the prognosis of patients with polycystic liver and kidney disease.

Conclusions

Combined liver and kidney transplantation (CLKT) is an effective treatment for patients with polycystic liver disease (PLD) and polycystic kidney disease (PKD) who progress to end-stage renal disease (ESRD). While postoperative complications such as graft rejection and infections can occur, they can generally be managed with appropriate interventions. Early liver transplantation in patients with severe malnutrition or sarcopenia is critical for improving recovery and reducing infection risk. Further studies are needed to refine immunosuppressive strategies and determine the optimal timing for transplantation in PLD/PKD patients.