Combined Liver-kidney Transplantation Research Articles

Immunosuppression in adult liver transplant recipients: a 2024 update from the Italian Liver Transplant Working Group.

Advances in surgical procedures and immunosuppressive therapies have considerably improved the outcomes of patients who have undergone liver transplantation in the past few decades. In 2020, the Italian Liver Transplant Working Group published practice-oriented algorithms for immunosuppressive therapy (IT) in adult liver transplant (LT) recipients. Due to the rapidly evolving LT field, regular updates to the recommendations are required. This review presents a consensus- and evidence-based update of the 2020 recommendations. The Italian Liver Transplant Working Group set out to address new IT issues, which were discussed based on supporting literature and the specialists' personal experiences. The panel deliberated on and graded each statement before consensus was reached. A series of consensus statements were formulated and finalized on: (i) oncologic indications for LT; (ii) management of chronic LT rejection; (iii) combined liver-kidney transplantation; (iv) immunosuppression for transplantation with an organ donated after circulatory death; (v) transplantation in the presence of frailty and sarcopenia; and (vi) ABO blood group incompatibility between donor and recipient. Algorithms were updated in the following LT groups: standard patients, critical patients, oncology patients, patients with specific etiology, and patients at high immunologic risk. A steroid-free approach was generally recommended, except for patients with autoimmune liver disease and those at high immunologic risk. The updated consensus- and evidence-based 2024 recommendations for immunosuppression regimens in adult patients with ABO-compatible LT address a range of clinical variables that should be considered to optimize the choice of the immunosuppression treatment in clinical practice in Italy.

1147 Long Term Outcomes Following Combined Liver-Kidney Transplantation

Abstract Aim Combined liver kidney transplant (CLKTx) is the mainstay of treatment for concurrent liver failure and end stage renal failure. The use of CLKTx has increased markedly since the introduction of the MELD (Model for End Stage Liver Disease) score for liver allocation. In this study we examined the long-terms outcomes of 25 years of CLKTx in our centre. Method From a database of all transplants from 1997 – 2022, 158 recipients of CLKTx were identified. Primary outcomes of interest were mortality and graft failure. Data was analysed in R studio and GraphPad prism. Results Overall patient survival was 89% at 1 year, 87% at 2 years, 81% at 5 years, 72% at 10 years and 50% at 20 years. The 20-year patient survival with a pre-transplant (preTx) MELD of <20 was 52%, with a preTx MELD of >20 associated with significantly lower 20-year patient survival of 26% (P<0.05). Death censored (dc) liver graft survival was 99% at 1 year, 98% at 2 years, 97% at 5 years and ten years, and 88% at 25 years. A donor age of <40 showed 20-year liver graft survival (dc) of (100%), which was significantly greater than the donor age >40 group (72%, P<0.05). Death censored kidney graft survival was 96% at 1 year, 95% at 2 and 5 years, 92% at ten years and 84% at twenty years post Tx. Conclusions We report favourable long-term outcomes following 25 years of CLKTx. Predictors for better long-term patient and graft survival include pre transplant MELD score and donor age.

#2932 Our experience in combined and simultaneous liver-kidney transplantation: recipient and kidney graft survival

Abstract Background and Aims Simultaneous combined liver-kidney transplantation is a definitive treatment in patients with terminal failure of both organs, but sometimes, assessing the indication for said combined transplantation can be difficult. The liver from the same donor as the kidney graft protects the kidney immunologically and this provides long-term follow-up with a lower risk of rejection. No such protection is observed when both organs come from different cadaveric donors. There are no differences in graft survival in simultaneous or isolated transplants (liver or kidney), being prolonged in both cases. However, patient survival is lower, due to the complexity of this procedure and the clinical characteristics of the patients. The main aim is to analyze the evolution of patients with combined and simultaneous liver-kidney transplantation in our center in terms of graft survival and overall survival of the recipient. Method It is a retrospective observational study. The computerized clinical history of 50 patients with combined liver-kidney transplantation was reviewed from August 1998 to November 2023. The data were recorded in an Excell-type database. Descriptive and inferential statistics were performed for the analysis. Results 50 combined liver-kidney transplants have been performed, of which 28 (56%) died, and 23 of them (82%) with the kidney graft functioning. The main causes of death were neoplasms (11 patients) and infections (7 patients). The survival of the patients at 5 years was approximately 70%. There were 5 cases of kidney graft loss, excluding death. Chronic rejection was the main cause (70-80%) of kidney graft loss. 60% received a kidney transplant again and died with the graft functioning; 20% died while on hemodialysis; and the remaining 20% are awaiting hemodialysis and are being studied for another kidney transplant. Conclusion Simultaneous liver and kidney transplantation is a good therapeutic option for patients with terminal disease of both organs. However, it is a complex procedure in patients with multiple comorbidities, which affects overall survival. In contrast, kidney graft survival is prolonged and many recipients die with functioning grafts. It seems to be related to the immunological protective function of the liver. Consequently, there are few rejections and, the vast majority are chronic rejection.

#1043 Metabolomics and proteomics study on kidney function post-liver transplantation

Abstract Background and Aims Hepatorenal syndrome (HRS) is a serious complication characterized by kidney dysfunction in patients with advanced liver disease. The pathophysiology of HRS is poorly understood and involves a combination of hemodynamic, circulatory, inflammatory, and hormonal factors. While some patients with HRS restore kidney function after liver transplantation (LT), others continue to have impaired kidney function. Understanding the mechanisms associated with persistent kidney dysfunction is essential for developing effective treatments and stratifying patients for combined liver-kidney transplantation versus LT only. Method We analyzed serum samples from 10 patients of the multicenter prospective study (INAID CTOT14). Five of them had no HRS and maintained an eGFR > 50 ml/min post-LT. One patient with HRS recovered kidney function post-LT. Four patients with HRS failed to regain kidney function at one- and two-months post-LT (eGFR < 30 ml/min). We categorized the five patients without HRS and one patient with recovered eGFR as Normal Kidney Function (NKF) group and the other four patients as Impaired Kidney Function (IKF) group. Serum samples were collected at one (visit 1) and two months (visit 2) post-LT and stored at −80°C until analysis. Both untargeted metabolomics and proteomics analysis were conducted using quantitative liquid chromatography tandem mass spectroscopy (LC-MS/MS) on Agilent® Q-TOF 6546. Data was analyzed by Agilent® Qualitative Workflow 10, Agilent® Profinder 10, MetaboAnalyst (V6.0), and Spectrum Mill MS software. Results A total of 150 metabolites were identified by LC-MS/MS based metabolomics. Principal component analysis (PCA) did not show significant differences between visit 1 and visit 2 samples (Fig. 1A). Therefore, visit 1 and visit 2 samples were analyzed together. With 12 samples in NKF and 8 samples in IKF group, the PCA score plot showed distinct clustering of the two groups (Fig. 1B). Volcano plot analysis was conducted to analyze metabolite differences between NKF and IKF. P-values were calculated using a Student's t-test, and differential metabolites were identified with a P-value cut-off of < .05 and a fold change > 2.0. The result revealed 37 downregulated and 13 upregulated metabolites when comparing NKF and IKF (Fig. 1C). Notably, creatinine was among the downregulated metabolites in the NKF group, validating the accuracy of our analysis. Untargeted proteomics analysis was also performed on all 20 samples. Using a P-value cut-off of .05 and a fold change >1.25, 43 proteins were found to be upregulated, and four proteins to be downregulated when comparing NKF to IKF. Fig. 2A lists the top 10 regulated proteins, with beta-2-microglobulin as the most significantly changed. Reactome® pathway analysis of these 47 proteins highlighted potential impacts on various biological pathways (Fig. 2B), providing potential valuable insights into the molecular alterations associated with kidney function post-LT. Conclusion Our comprehensive metabolomics and proteomics study characterized the molecular alterations associated with kidney function post-LT. The identified metabolites and proteins may provide valuable insights for understanding persistent kidney damage. Future research is warranted to confirm and correlate these findings with clinical outcomes, enhancing the applicability and significance of our results in the broader context of HRS and LT.

#2403 Impact of pregnancy on kidney transplant recipients

Abstract Background and Aims Kidney transplantation (KT) provides an opportunity to increase fertility in women with chronic kidney disease and gestational desire. Lack of knowledge about obstetric complications and implications for the graft may lead to discourage pregnancy for these women. Although the incidence of pregnancy is rising in women receiving KT, the impact that it may have on the graft function is unknown. Method We conducted an observational, retrospective, single-centre study of a cohort of kidney transplant recipients (KTR) who became pregnant between 2007 and 2022. Clinical and analytical parameters were evaluated before, during and after pregnancy. The main aim was to assess the long-term impact of pregnancy on the graft by analysing renal function 3 years after pregnancy. Results We included 25 women receiving a KT between 1990 and 2018, among which 72% (n = 18) were transplanted from a deceased donor. 2 women (8%) received a combined liver-kidney transplant and 2 women (8%) a simultaneous pancreas-kidney transplant. Maintenance immunosuppression before conception included teratogenic drugs in 68% of cases [12 of them (48%) received mycophenolate mofetil and 5 of them (20%), mTOR inhibitors]. Planned withdrawal was only applied in 50.0% of pregnancies (n = 15). 30 pregnancies were identified (5 patients had 2 post-transplant pregnancies). Median age at gestation was 35 years [interquartile range (IQR) 33-39]. 5 conceptions required assisted reproductive technology. The main complications were gestational hypertension in 4 KTR (13.3%) and preeclampsia in 7 pregnancies (23.3%). 60% of neonates (n = 18) were preterm births (36 [IQR 34-37] weeks of pregnancy at birth) and 44% (n = 12) had low birth weight (2530 [IQR 2283-2950] grams). No foetal malformations were described. Due to physiological changes, a significant increase in estimated glomerular filtration rate (eGFR) was observed in the first and the second trimester of pregnancy (61 [IQR 50-91] ml/min and 70 [IQR 50-90] ml/min, respectively vs. baseline eGFR 59 [IQR 47-77] ml/min; p 0.001]. However, eGFR was equal to the previous one in the third trimester of pregnancy (60 [IQR 44-69] ml/min vs. 59 [IQR 47-77] ml/min; p 0.322). Median proteinuria remained below 0.5 g/day throughout pregnancy, without significant variation. Immunosuppression regimen during pregnancy was mainly based on a combined therapy of steroids, calcineurin inhibitors and azathioprine (21 KTR, 70%). Tacrolimus dose increase (median 63.6% [IQR 33.3-90.0%]) was necessary to maintain proper drug levels throughout gestation. Kidney graft function showed a decline in the first and second year after pregnancy compared to baseline function (54 [IQR 35-77] ml/min and 55 [IQR 36-75] ml/min vs. 59 [IQR 47-77] ml/min; p 0.018 and p 0.021, respectively]. Nevertheless, by the third year post-pregnancy, eGFR was similar to the baseline function (62 [IQR 43-73] ml/min vs. 59 [IQR 47-77] ml/min; p 0.365]. Likewise, annual eGFR variation was comparable during 3 years before (+1.0 ml/min/year) and 3 years after pregnancy (−0.9 ml/min/year), hence no worsening was observed after gestation (p 0.78). No differences were observed in proteinuria either (baseline proteinuria 0.17 [IQR 0.13-0.3] g/day vs. third-year proteinuria 0.21 [IQR 0.15-0.34] g/day; p 0.938). Only 5 women had a baseline serum creatinine above current recommendations for pregnancy (>1.5 mg/dl) and only 3 women presented baseline proteinuria > 0.5 g/day. In this group (n = 7), pregnancy occurred later after KT (96.0 [IQR 80.9-213.0] vs. 46.0 [IQR 16.0-67.5] months; p 0.024). The only 2 graft losses in the cohort were in this group. Both were attributed to transplant glomerulopathy, and they occurred at years 3 and 5 after pregnancy. On the other side, in this group there were no other baseline differences or obstetrical complications [Table 1]. Conclusion Pregnancy does not normally affect graft function and it stabilises within 3 years after gestation. It is important to increase data on women with suboptimal graft function to determine the direct implications that pregnancy may have on these KTRs.

Outcomes of Combined Liver-Kidney Transplantation – Single Center Experience

There is continuous growth of combined liver-kidney transplantation (CLKTx) numbers with remarkable outcomes, especially among patient with liver cirrhosis and end-stage renal disease. The aim was to present a single center experience. Twenty patients (9 males) with a mean age of 48 (range: 20-62) years underwent CLKTx from 2005 to 2022. Indications were polycystic liver and kidney diseases (ADPKD) in 12 cases, cirrhosis due to hepatitis (4 patients), and 1 case of amyloidosis, alcoholic liver disease, nonalcoholic steatosis, and congenital hepatic fibrosis with concomitant glomerulonephritis. After hepatectomy, half of the patients had orthotopic liver transplantation with piggy-back technique, and the other had conventional technique. All but 1 recipient had biliary end-to-end anastomosis. 3 patients had preemptive kidney graft transplantation. 4 underwent simultaneous right-side nephrectomy due to volume of the right kidney. Kidney was transplanted from the separate incision after abdominal closure with typical anastomoses. Tacrolimus, mycophenolate mofetile, basiliximab, and steroids were applied for all recipients. Mean follow-up was 57.7 ± 54 months. No primary non-function of the grafts occurred. Delayed kidney graft function (DGF) occurred in 8 patients. Three-month, 1-year, and 5-year cumulative survival rates were: 90%, 80%, and 72% respectively. None of the patients required retransplantation, and 1 recipient returned to hemodialysis 19 months after transplantation. Preemptive kidney transplantation and simultaneous right-side nephrectomy were not significant for DGF and recipient survival. No deaths within the first year occurred in piggy-back technique. CLKTx is safe and effective in the treatment of both liver and kidney failure.

(1206) - Impella 5.5 Assisted Combined Liver-Kidney Transplantation

(1206) - Impella 5.5 Assisted Combined Liver-Kidney Transplantation

Bone health in children with primary hyperoxaluria type 1 following liver and kidney transplantation.

Primary hyperoxaluria type 1 is characterized by hepatic oxalate overproduction, leading to nephrocalcinosis, kidney stones, kidney failure and systemic oxalosis, including oxalate osteopathy. Combined liver-kidney transplantation (CLKT) and kidney after liver transplantation (KALT) were established therapeutic options to stop the devastating consequences of oxalate bone disease. We describe a retrospective cohort of 10 children with PH1who were referred to our hospital from different countries for combined transplantation. Demographic and clinical data were collected and symptoms of bone disease, conventional radiological examinations, plasma oxalate levels and other determinants of calcium-phosphate metabolism were compared pre and post transplantation. Ten patients (7 male, median age 5.8 years, median follow-up time 8.1 years) were included in this study. Seven patients were diagnosed with infantile oxalosis and 9 patients received an intensified dialysis regime prior to transplantation. In one patient the transplanted kidney never achieved primary function and the boy remained on HD. All other patients remained without graft failure and retained stable kidney and liver function. Prior to transplantation, seven patients suffered from severe skeletal pain and three children presented with 1-3 series of pathological fractures. Pathological fractures did no longer occur in children who underwent successful CLKT or KALT. Plasma oxalate levels dropped within 6 months following Tx. Determinants of calcium-phosphorus metabolism did not differ significantly in comparison to other HD children. Seven of ten children showed a restricted growth at the time of transplantation and presented a moderate catch-up-growth at the time of last follow-up. Patients with PH1 suffer from severe consequences of a disturbed bone metabolism. However, bone health and growth can partially improve following CLKT/KALT.

Initial Experience of Anesthetic Management in Combined Liver-Kidney Transplantation: A Case Report

In this case report, we present a successful combined liver-kidney transplantation (CLKT) performed on a 41-year-old female with end-stage liver and renal disease. The patient, previously undergoing liver transplantation and regular hemodialysis, underwent CLKT with a focus on specific anesthesia management strategies. Key aspects included the use of desflurane for anesthesia, balanced crystalloid solutions for fluid management, and careful monitoring of hemodynamics without intraoperative renal replacement therapy. Despite substantial intraoperative fluid and blood product administration, careful management ensured stable vital signs and acid-base balance. The patient's postoperative recovery was notable for significant improvements in liver and renal functions, demonstrated by decreased creatinine and bilirubin levels, and improved estimated glomerular filtration rate, without the need for postoperative dialysis. This case underscores the effectiveness of CLKT in patients with concurrent liver and renal dysfunction, highlighting the importance of tailored anesthesia and fluid management strategies. The report contributes to the limited literature on anesthesia in CLKT, providing insights for better outcomes in such complex surgical procedures.

Combined liver-kidney transplantation in pediatric patients.

Combined liver-kidney transplantation (CLKT) is a surgical procedure that involves transplanting both liver and kidney organs. There are two types of CLKT: simultaneous liver-kidney transplantation (smLKT) and sequential LKT (sqLKT). CLKT accounts for a small percentage of liver transplantations (LTs), particularly in pediatric cases. Nevertheless, the procedure has demonstrated excellent outcomes, with high survival rates and lower rejection rates. The main indications for CLKT in pediatric patients differ somewhat from that in adults, in which end-stage kidney disease after LT is the major indication. In children, congenital diseases are common reason for performing CLKT; the examples of such diseases include autosomal recessive polycystic kidney disease with congenital hepatic fibrosis which equally affects both organs, and primary hyperoxaluria type 1, a primary liver disease leading kidney failure. The decision between smLKT or sqLKT depends on the dominant organ failure, the specific pathophysiology, and available organ sources. However, there remain significant surgical and societal challenges surrounding CLKT. Innovations in pharmacology and genetic engineering have decreased the necessity for CLKT in early-diagnosed cases without portal hypertension or kidney replacement therapy. Nonetheless, these advancements are not universally accessible. Therefore, decision-making algorithms should be crafted, considering region-specific organ allocation systems and prevailing medical environments.

Primary hyperoxaluria: a case series

BackgroundPrimary hyperoxaluria (PH) is a rare genetic disorder characterized by the excessive production and accumulation of oxalate. We present five cases of PH, each exhibiting varying manifestations of the disorder including a case presenting as postpartum kidney failure. Notably, three of these cases involve a previously unreported mutation.Case presentationsWe evaluated five Indian patients who presented with varying manifestations of PH. The first case, a 30 year old woman, presented as post-partum kidney failure and was found to be having oxalate nephropathy precipitated by dietary oxalate overload in the setting of previously undiagnosed PH. Genetic analysis revealed a previously unreported mutation in the alanine-glyoxylate aminotransferase gene. The patient underwent simultaneous kidney liver transplant. The second and third cases, 26 and 28 year old women respectively, were asymptomatic siblings of the first patient, who were diagnosed through screening. The fourth case is a 12 year boy with PH type 1 presenting as nephrolithiasis and rapidly worsening kidney function requiring combined kidney liver kidney transplant. Case 5 is a 6 year old male child with type 2 PH presenting with nephrolithiasis, nephrocalcinosis and normal kidney function. All the patients were born to consanguineous parents.ConclusionsDue to limited clinical suspicion and inadequate diagnostic resources in certain countries with limited resources, it is possible for PH to go undiagnosed. The manifestations of the disease can range from no noticeable symptoms to severe disease. Interestingly, in some individuals with primary hyperoxaluria, the disease may not exhibit any symptoms until it is triggered by a high intake of dietary oxalate.

#2997 ASSESSMENT OF FRACTURE RISK IN KIDNEY TRANSPLANT RECIPIENTS BY FRAX SCORE WITHOUT BONE MINERAL DENSITY

Abstract Background and Aims Bone disease post-transplantation is a major cause of morbidity in kidney transplant (KT) recipients, with a significantly higher risk of fractures and mortality. This study investigated the added value of calculated 10-year fracture risk for major osteoporotic fracture (MOF) and hip fracture by frax score with an assessment of risk factors in KT recipients. Methods A cross-sectional study included 71 live-related KT recipients. Demographic, clinical, and laboratory data were recorded. The 10-year fracture risk for MOF and hip fracture were calculated using frax score without bone mineral density in recipients who completed at least 1 year after KT. Results The prevalence of MOF (>3% risk of fracture) was 14.1%(10 patients), MOF (<3% risk of fracture) was 85.9% (61 patients). A high hip fracture score (>3% risk of hip fracture) was in 10% (1 patient). There was a significant difference between both groups (>3%vs <3% fracture risk) in age, MOF score, hip fracture score, and serum albumin p-value were <0.00001, <0.00001, 0.000134, and 043009 respectively. The analysis of demographic data of the patients with a score (>3% fracture risk) showed that 70% were males (7 patients), 50% (5 patients) had BMI>30 and the main cause of ESRD pre-transplant was lupus nephritis and glomerulonephritis in 50% (5 patients) that exposed for long periods of immune suppression pre-transplant. In 80% (8 patients) were 1st transplant, 10% (1 patient) were 2nd transplant, and 10% (1 patient) was a combined liver-kidney transplant. The rejection episode was zero%. There was a significant difference in patients' fracture risk >3% in phosphorus pre-transplant versus post-transplant p-value 0.01. Conclusion Frax score without bone mineral density has shown a low percent of fracture risk (<3%) in most kidney transplant recipients and high scores were associated with high BMI, phosphorus, and exposure pre-transplant to immune suppression.

Long-term outcomes of combined liver-kidney transplantation in pediatric patients: A single center experience

Long-term outcomes of combined liver-kidney transplantation in pediatric patients: A single center experience

Liver Only Living Donor Transplantation for Polycystic Disease in a Patient on Chronic Hemodialysis: Case Report

Polycystic liver disease (PLD) is characterized by the progressive development of polycystic lesions in the kidney and the liver, possibly resulting in dual organ failure. We indicated living donor liver transplantation (LDLT) for a patient with end-stage liver and kidney disease (ELKD) due to PLD on uncomplicated chronic hemodialysis. A 63-year-old man with ELKD and uncontrolled massive ascites due to PLD and hepatitis B on uncomplicated chronic hemodialysis was referred to us with a single possible 47-year-old female living donor. Because of the necessity of right lobe liver procurement from this small middle-aged donor and uncomplicated hemodialysis on this recipient, we considered LDLT, rather than dual organ transplantation, could be the most well-balanced option to save the life of this recipient with acceptable risk limits for this donor. A right lobe graft with 0.91 for graft recipient weight ratio was implanted with an uneventful operative procedure under intra- and postoperative continuous hemodiafiltration. The recipient was rescheduled on routine hemodialysis on day 6 after transplantation and recovered with a gradual decrease in ascites output. He was discharged on day 56. He continues to have a very good liver function and quality of life without ascites and uncomplicated routine hemodialysis 1 year after transplantation. The living donor was discharged 3 weeks after surgery and is also doing well. Although combined liver-kidney transplantation from a deceased donor could be the best option for ELKD due to PLD, LDLT can also be an acceptable option for ELKD with uncomplicated hemodialysis, considering the double equipoise theory for both lifesaving of the recipient and acceptable donor risk.

Living Donor Liver Transplantation Alone Is Not Inferior to Combined Kidney Liver Transplant for Cirrhotic Patients With Chronic Kidney Disease

Chronic kidney disease (CKD) is common in patients with chronic liver disease (CLD) as is acute kidney injury (AKI). The differentiation between CKD vs AKI is often difficult and sometimes the both may coexist. A combined kidney-liver transplant (CKLT) may result in a kidney transplant in patients whose renal function is likely to recover or at least who have stable renal function post-transplant. We retrospectively enrolled 2742 patients who underwent living donor liver transplant at our center from 2007 to 2019. This audit was carried out in liver transplant recipients with CKD 3 to 5 who underwent either liver transplant alone (LTA) or CKLT to look at outcomes and long-term evolution of renal function. Forty-seven patients met the medical eligibility criteria for CKLT. Of the 47 patients, 25 underwent LTA and the rest 22 underwent CKLT. The diagnosis of CKD was made according to the Kidney Disease: Improving Global Outcomes classification. Preoperative renal function parameters were comparable between the 2 groups. However, CKLT patients had significantly lower glomerular filtration rates (P=.007) and higher proteinuria (P=.01). Postoperatively, renal function, and comorbidities were comparable between the 2 groups. Survival was similar at 1, 3, and 12 months, respectively (log-rank; P=.84,=.81, and=.96, respectively). At the end of the study period, 57% of patients who survived in LTA groups had stabilized renal function (Creatinine=1.8 ± 0.6 mg/dL). Liver transplant alone is not inferior to CKLT in living donor situations. Renal dysfunction is stabilized in the long term whereas long-term dialysis may be carried out in others. Living donor liver transplantation alone is not inferior to CKLT for cirrhotic patients with CKD.

Human leukocyte antigen antibodies and leukocyte antigen/killer-cell immunoglobulin-like receptor genes are important in transplant immunology in the liver

Many mechanisms have been proposed to explain the hypothetical state of hepatic tolerance, which is described by eventual imbalances or deregulation in the balance of cytokines, mediators, effectors, and regulatory cells in the complex milieu of the liver. In this section, we will comment on the importance of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) as well as the compatibility and pairings of HLA and killer-cell immunoglobulin-like receptor (KIR) genotypes in the evolution of liver transplantation. Thus, HLA compatibility, viral infections, and HLA-C/KIR combinations have all been linked to liver transplant rejection and survival. There have been reports of increased risk of acute and chronic rejection with ductopenia, faster graft fibrosis, biliary problems, poorer survival, and even de novo autoimmune hepatitis when DSAs are present in the recipient. Higher mean fluorescence intensity (MFI) values of the DSAs and smaller graft size were associated with poorer patient outcomes, implying that high-risk patients with preformed DSAs should be considered for selecting the graft placed and desensitization methods, according to the investigators. Similarly, in a combined kidney-liver transplant, a pretransplant with a visible expression of several DSAs revealed that these antibodies were resistant to treatment. The renal graft was lost owing to antibody-mediated rejection (AMR). The HLA antigens expressed by the transplanted liver graft influenced antibody elimination. Pathologists are increasingly diagnosing AMR in liver transplants, and desensitization therapy has even been employed in situations of AMR, particularly in patients with DSAs in kidney-hepatic transplants and high-class II MFI due to Luminex. In conclusion, after revealing the negative impacts of DSAs with high MFI, pretransplant virtual crossmatch techniques may be appropriate to improve evolution; however, they may extend cold ischemia periods by requiring the donor to be typed.

Long-term outcomes after pre-emptive liver transplantation in primary hyperoxaluria type 1.

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disease caused by the liver defect of oxalate metabolism, which leads to kidney failure and systemic manifestations. Until recently, liver transplantation was the only definitive treatment. The timing of liver transplantation can be early, while kidney function is still normal (pre-emptive liver transplantation-PLT), or when the patient reaches stage 5 chronic kidney disease (CKD) and needs combined liver-kidney transplantation. We aimed to determine the long-term kidney outcomes of PLT in PH1 patients. A retrospective single-center study of PH1 patients who were followed in our center between 1997 and 2017. We compared the kidney outcomes of patients who underwent PLT to those who presented with preserved kidney function and did not undergo PLT. Out of 36 PH1 patients, 18 patients were eligible for PLT (eGFR > 40mL/min/1.73 m2 at the time of diagnosis). Seven patients underwent PLT (PLT group), while 11 continued conservative treatments (PLTn group). In the PLT group, the median eGFR at the time of PLT and at the end of the follow-up period (14-20years) was 72 (range 50-89) and 104 (range 86-108) mL/min/1.73 m2, respectively, and no patient died or reached stage 5 CKD. In the PLTn group, eight patients (72.7%) reached stage 5 CKD (median time to kidney replacement therapy was 11years), and two patients died from disease complications (18.2%). Pre-emptive liver transplantation preserved kidney function in patients with PH1 in our cohort. Early intervention can prevent kidney failure and systemic oxalosis in PH1. A higher resolution version of the Graphical abstract is available as Supplementary information.

Combined Liver–Kidney Transplantation in High Immunologic Risk Recipients: Kidney Graft Evolution

Candidates for combined liver-kidney transplant frequently present pretransplant HLA sensitization in most cases related to elevated prior transfusion requirements. The urgency criterion and the evidence of the protective effect at the immunologic level of the liver graft open the possibility of carrying out the combined transplant in patients with an incompatible crossmatch. The single-center experience presented here describes the patient profile and kidney graft evolution observed in this highly sensitized group. Descriptive study of a series of 4 cases of patients with positive crossmatch results who received a simultaneous liver-kidney transplant at our center. Demographic characteristics and clinical information were collected and detailed. Before the transplant, 2 patients presented HLA class I antibodies and the other 2 showed both class I and II. The post-transplant crossmatch result was negative in 2 of the 4 patients. All received induction with Thymoglobulin. In the 2 patients in whom the crossmatch remained positive, treatment with plasmapheresis, intravenous immunoglobulins and rituximab was initiated, after which the crossmatch resulted negative. During follow-up, anti-HLA antibodies were monitored, with the presence of mainly class I antibodies with variable mean fluorescence intensity being detected in all but 1 patient. Renal graft function remained stable throughout the tracing without objectifying histologic signs of rejection during the first 6 months of evolution. In our experience, combined liver-kidney transplant in sensitized patients with an incompatible crossmatching test has presented satisfactory outcomes. Close clinical and analytical monitoring is essential.

Isolated Hepatic Chronic Ductopenic Rejection Requiring Liver Retransplant in the Absence of Kidney Graft Rejection After Combined Liver-Kidney Transplant: A Case Report

The liver is considered the most immunotolerant organ among all solid-organ transplants. Liver transplant recipients have a lower incidence of rejection and better outcomes after episodes of rejection, with spontaneous operational tolerance developing in up to 20%. In multiorgan transplants, a protective effect of the liver allograft on simultaneously transplanted organs from the same donor has been demonstrated. We describe an unusual case of isolated liver allograft rejection in a patient with polycystic liver and kidney disease who received a combined liver-kidney transplant from the same donor. After initial discharge from the hospital, our patient had 2 episodes of biopsy-proven late acute cellular rejections, despite higher levels of immunosuppression required for her kidney allograft, which were addressed with pulsed steroid therapy. She had no evidence of ischemic cholangiopathy on imaging. Later, a subsequent liver biopsy demonstrated features consistent with chronic ductopenic rejection. She was eventually listed for liver retransplant and has recently received a second liver transplant while continuing to have no concerns with her kidney allograft function. Examination of the explanted liver confirmed graft loss from chronic ductopenic rejection. The exact reasons why our patient developed acute graft rejection progressing to chronic end-stage rejection of the liver allograft despite not developing graft rejection in the kidney allograft from the same donor remains elusive. Our experience demonstrates that graft tolerance in multiorgan transplant recipients can be organ specific and despite the belief of "immunologic privilege," isolated liver allograft rejection can occur in multiorgan transplant, resulting in graft loss.

A case report of invasive infantile primary hyperoxaluria type 1 and literature review.

Infantile primary hyperoxaluria type 1 (PH1) is the most devastating primary hyperoxaluria (PH) subtype as it leads to early end-stage kidney disease (ESKD) associated with high mortality. We report a case of a three-month-old female Chinese infant who was diagnosed with PH1 by renal biopsy and genetic studies. She carried two heterozygous mutations in the alanine-glyoxylate and serine pyruvate aminotransferase (AGXT) gene, one of which has never been previously reported. The patient had multiple organ failures caused by kidney failure, which was improved by extracorporeal membrane oxygenation and continuous renal replacement therapy. However, her primary disease responded poorly to conservative treatment. Fortunately, after waiting for four months, the patient underwent a successful combined liver-kidney transplantation and has progressed well so far. This case highlights the importance of suspecting PH in infant patients with ESKD of uncertain etiology, as early initiation of therapy prevents poor outcomes.