Combined Liver-kidney Transplantation Research Articles

Insuffisance rénale après transplantation hépatique

One third of cirrhotic patients present impaired kidney function. It has multifactorial causes and has a harmful effect on patients’ morbi-mortality before and after liver transplant. Kidney function does not improve in all patients after liver transplantation and liver-transplant recipients are at high risk of developing chronic kidney disease. Causes for renal dysfunction can be divided in three groups: preoperative, peroperative and postoperative factors. To date, there is no consensus for the modality of evaluation the risk for chronic kidney disease after liver transplantation, and for its prevention. In the present review, we describe the outcome of kidney function after liver transplantation, and the prognostic factors of chronic kidney disease to determine a risk stratification for each patient. Furthermore, we discuss therapeutic options to prevent kidney dysfunction in this setting, and highlight the indications of combined liver-kidney transplantation.

Missed diagnosis of oxalosis with disastrous consequences. Case reports of a father and daughter

Background: Hyperoxalosis is a rare disease that originates from a defect in a liver enzyme and results in renal failure, if not diagnosed in time. Once end-stage renal disease is established, a transplant is the treatment of choice. But a kidney-only transplant can fail due to the mobilization of the excess oxalates in the tissue, and many authorities recommend a combined kidney-liver transplant. Case Presentation: We describe a case where the diagnosis of oxalosis was missed, resulting in renal transplant failure and excision of the graft. The diagnosis was made only on noting florid heterotopic calcification. A renal transplant was performed due to end-stage renal disease, but graft failure occurred and had to be excised due to recurrent oxalosis, again without diagnosis, despite imaging and graft biopsy. It was only when muscle calcification was noted for an unrelated indication that a diagnosis was made. The case highlights the importance of excluding all causes of nephrocalcinosis, including rare ones like oxalosis, in the management of chronic renal disease. Conclusion: We hope to alert the physician to consider primary hyperoxalosis as a differential diagnosis in renal failure patients with recurrent calcium oxalate renal stones and/or nephrocalcinosis.

Long-Term Transplantation Outcomes in Patients With Primary Hyperoxaluria Type 1 Included in the European Hyperoxaluria Consortium (OxalEurope) Registry

IntroductionIn primary hyperoxaluria type 1 (PH1), oxalate overproduction frequently causes kidney stones, nephrocalcinosis, and kidney failure. As PH1 is caused by a congenital liver enzyme defect, combined liver–kidney transplantation (CLKT) has been recommended in patients with kidney failure. Nevertheless, systematic analyses on long-term transplantation outcomes are scarce. The merits of a sequential over combined procedure regarding kidney graft survival remain unclear as is the place of isolated kidney transplantation (KT) for patients with vitamin B6-responsive genotypes.MethodsWe used the OxalEurope registry for retrospective analyses of patients with PH1 who underwent transplantation. Analyses of crude Kaplan–Meier survival curves and adjusted relative hazards from the Cox proportional hazards model were performed.ResultsA total of 267 patients with PH1 underwent transplantation between 1978 and 2019. Data of 244 patients (159 CLKTs, 48 isolated KTs, 37 sequential liver–KTs [SLKTs]) were eligible for comparative analyses. Comparing CLKTs with isolated KTs, adjusted mortality was similar in patients with B6-unresponsive genotypes but lower after isolated KT in patients with B6-responsive genotypes (adjusted hazard ratio 0.07, 95% CI: 0.01–0.75, P = 0.028). CLKT yielded higher adjusted event-free survival and death-censored kidney graft survival in patients with B6-unresponsive genotypes (P = 0.025, P < 0.001) but not in patients with B6-responsive genotypes (P = 0.145, P = 0.421). Outcomes for 159 combined procedures versus 37 sequential procedures were comparable. There were 12 patients who underwent pre-emptive liver transplantation (PLT) with poor outcomes.ConclusionThe CLKT or SLKT remains the preferred transplantation modality in patients with PH1 with B6-unresponsive genotypes, but isolated KT could be an alternative approach in patients with B6-responsive genotypes.

Liver or Kidney Transplantation After SARS-CoV-2 Infection: Prevalence, Short-term Outcome, and Kinetics of Serum IgG Antibodies.

Background.There is a paucity of data on the prevalence, adequate timing, and outcome of solid organ transplantation after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and the kinetics of immunoglobulin G (IgG) antibodies in these patients.Methods.SARS-CoV-2 antinucleocapsid (N) IgG and polymerase chain reaction via a nasopharyngeal swab were analyzed in all patients within 24 h before liver or kidney transplantation. Kinetics of IgG antibodies were analyzed and compared with an immunocompetent cohort.Results.Between May 1, 2020, and March 18, 2021, 168 patients underwent liver or kidney transplantation in our center, of which 11 (6.54%) patients with a previous SARS-CoV-2 infection were identified. The median interval between SARS-CoV-2 infection and transplantation was 4.5 mo (range, 0.9–11). After a median posttransplant follow-up of 4.9 mo, 10 out of 11 patients were alive without clinical signs of viral shedding or recurrent or active infection. One patient without symptom resolution at time of transplantation died after combined liver-kidney transplantation. In 9 out of 11 patients with previously polymerase chain reaction-confirmed infection, SARS-CoV-2 anti-N and antispike (S) IgG were detectable at day of transplantation. Absolute levels of anti-N and anti-S IgG were positively correlated, declined over time in all patients, and were significantly lower compared with immunocompetent individuals. All patients remained anti-S IgG positive until the last posttransplant follow-up, whereas 3 patients became anti-N negative.Conclusions.We observed an uncomplicated course of liver or kidney transplantation after SARS-CoV-2 infection in selected patients. Although having lower absolute IgG antibody levels than immunocompetent individuals, all seroconverted patients remained anti-S IgG positive. These encouraging data need validation in larger studies.

Extreme living donation: A single center simultaneous and sequential living liver-kidney donor experience with long-term outcomes under literature review.

Living liver and kidney donor surgeries are major surgical procedures applied to healthy people with mortality and morbidity risks not providing any direct therapeutic advantage to the donor. In this study, we aimed to share our simultaneous and sequential living liver-kidney donor experience under literature review in this worldwide rare practice. Between January 2007 and February 2018, a total of 1109 living donor nephrectomies and 867 living liver donor hepatectomies were performed with no mortality to living-related donors. Eight donors who were simultaneous or sequential living liver-kidney donors in this time period were retrospectively reviewed and presented with their minimum 2- year follow-up. Of the 8 donors, 3 of them were simultaneous and 5 of them were sequential liver-kidney donation. All of them were close relatives. Mean age was 39 (26-61) years and mean BMI was 25.7 (17.7-40). In 3 donors, right lobe, in 4 donors, left lateral sector, and in 1 donor, left lobe hepatectomy were performed. Median hospital stay was 9 (7-13) days. Two donors experienced early and late postoperative complications (Grade 3b and Grade 1). No mortality and no other long-term complication occurred. Expansion of the donor pool by utilizing grafts from living donors is a globally-accepted proposition since it provides safety and successful outcomes. Simultaneous or sequential liver and kidney donation from the same donor seems to be a reasonable option for combined liver-kidney transplant recipients in special circumstances with acceptable outcomes.

Kidney Failure after Liver Transplantation

One-third of patients with cirrhosis present kidney failure (AKI and CKD). It has multifactorial causes and a harmful effect on morbidity and mortality before and after liver transplantation. Kidney function does not improve in all patients after liver transplantation, and liver transplant recipients are at a high risk of developing chronic kidney disease. The causes of renal dysfunction can be divided into three groups: pre-operative, perioperative and post-operative factors. To date, there is no consensus on the modality to evaluate the risk of chronic kidney disease after liver transplantation, or for its prevention. In this narrative review, we describe the outcome of kidney function after liver transplantation, and the prognostic factors of chronic kidney disease in order to establish a risk categorization for each patient. Furthermore, we discuss therapeutic options to prevent kidney dysfunction in this context, and highlight the indications of combined liver–kidney transplantation.

Combined liver–kidney transplantation with positive crossmatch: Role of delayed kidney transplantation

BackgroundPositive crossmatch (XM+) combined liver–kidney transplantation due to preformed donor-specific human leukocyte antigen antibodies has produced mixed results. We sought to understand the role of delayed kidney transplant approach in XM+ combined liver–kidney transplantations. MethodsXM+ combined liver–kidney transplantations were retrospectively reviewed. T- and B-cell XM, complement-dependent cytotoxic crossmatch, and flow cytometric crossmatch were performed prospectively. ResultsOf 183 combined liver-kidney transplantations performed (2002–2019), 114 (62%) were with “delayed” kidney transplant approach and 19 (19 of 183, 10%) were XM+. Of 19 XM+ combined liver–kidney transplantations, kidney transplant was “delayed” in 14 by an average of 47 hours (range 24–64 hours) from liver transplant. There was a significant reduction in both class I (mean pre–liver transplant mean fluorescence intensity (MFI) 26,230 versus mean post–liver transplant and pre–delayed kidney transplant MFI 3,272, P = .01) and total MFI (mean pre–liver transplant MFI 27,233 vs mean post liver transplant and predelayed kidney transplant MFI 11,469, P = .01). However, there was no significant change in the MFI of class II donor-specific antibodies (mean pre–liver transplant MFI 17,899 versus post-liver transplant and pre–delayed kidney transplant MFI 14,341, P = .19). None of XM+ delayed kidney transplants had delayed graft function, and there was no antibody-mediated rejection. One-year patient survival for the XM+ combined liver–kidney transplantation with delayed kidney transplant approach was 92.9%, which is comparable to patient survival of XM– combined liver–kidney transplantation. Whereas patient survival in recipients before “delayed” approach (“simultaneous”; n = 5) was 40% when liver–kidney transplants were performed simultaneously (P = .06). ConclusionIn sensitized combined liver-kidney transplantation recipients, the “delayed” kidney transplant approach is associated with a significant reduction in total and class I donor-specific antibodies after liver transplant before kidney transplant, enabling therapeutic interventions such as plasmapheresis, if needed, providing optimal outcomes similar to crossmatch recipients.

MO772PRIMARY AND SECONDARY HYPEROXALURIA IN CHRONIC DIALYSIS PATIENTS: FOCUS ON VASCULAR ACCESS

Abstract Background and Aims Hyperoxaluria is a rare metabolic disorder chacterized by widespread calcium oxalate deposition, if plasmatic oxalate level (pOx) overcomes saturation threshold. It could be primary (PH), a recessive disease associated with mutation of the liver enzyme LDH, or secondary (SH), in 75% due to intestinal malabsorption. Urolithiasis could be the first complication, and renal involvement could progress until end-stage renal disease (ESRD). Mean pOx is higher in chronic dialysis patients than healthy individuals because of impaired renal clearance. Oxalate molecular weight (MW) is 88 Da and its clearance is that of low MW uremic toxins. Our aim is to assess an association between arteriovenous fistula (AVF) failures and Hyperoxaluria. Method In the period between 1/1/2004 and 12/31/2020, diagnosis of Hyperoxaluria was carried out in 6 patients out of 1530 chronic dialysis patients (0.39%). The median age of patients was 65.5 [26-72] years, the male/female ratio was 3:3 and the median dialysis vintage was 36 [1-181] months. Three patients come to nephrological referral at stage 5 of CKD while 1 patient came to Italy when chronic HD was already started. At that time pOx was not considered. In these 4 patients the presumptive diagnosis of ESRD was urolithiasis and diagnosis of Hyperoxaluria was carried out after the beginning of chronic dialysis, when pOx and genetic analysis were performed. In 1 case biopsy on the kidney graft and in 1 case kidney biopsy after nephrectomy were performed: oxalate deposition was detected. For 2/6 patients diagnosis was carried out after biopsy of native kidneys before starting dialysis. All patients started medical therapy for hyperoxaluria. Five out of 6 patients were eligible to HD, 1/6 to PD. AVF was judged the first choice vascular access. Results PH was diagnosed in 3/6 patients: mutations were detected on chromosome 2. Malabsorption secondary to short bowel syndrome and chronic pancreatitis could be assumed as causes of SH in 3 patients. Patient 1 underwent 2 combined liver-kidney transplantation: the first failed by arterial grafts thrombosis and the second by renal primary non-function but the liver was still functioning, he died on HD after 12 years. Patient 2 underwent liver and kidney transplantation and she is nowadays dialysis-free. The median pOx pre-dialysis and before diagnosis was 165 [98-259] umol/L (Table 1). Patients on chronic HD underwent median of 3 [2-5] AVF interventions. Nine AVFs were distal and 4 were proximal. The most frequent complication was AVF thrombosis despite ASA treatment: half of the cases showed secondary AVF non-function, the other half of AVFs failed to mature. Six tunneled cuffed permanent catheters (TCCs) as definitive vascular access were successfully placed in the 5 patients on chronic HD. Warfarin therapy was started to avoid TCCs thrombosis. The median survival of TCCs was 9.5 [3-48] months. All the patients had a history of deep venous thrombosis (DVT). Conclusion To our knowledge this is the first case series of multiple AVF failures in patients with hyperoxaluria. In our experience TCCs show longer survival then AVF in this group of patients, even if it could not be excluded the role of warfarin in favoring this result. Even though a link between hyperoxaluria and thrombosis is well established, the exact underlying mechanism is still uncleared. The role of PD as dialysis technique of “first choice” should be enhanced also when residual renal function is abolished. In ESRD patients with urolithiasis, diagnosis of Hyperoxaluria should be ruled out before AVF placement.

MO950SIMULTANEOUS LIVER-KIDNEY TRANSPLANT. SIXTEEN YEARS OF MONOCENTRIC EXPERIENCE

Abstract Background and Aims Combined liver-kidney transplant is the best treatment for patients with hepatic and renal failure, even though some studies reported a poor patient survival. The aim of our study is to summarize the clinical characteristics of subjects who undergo simultaneous combined liver-kidney transplantation (SLKT) for advanced liver and kidney disease. Furthermore, we evaluated patient and kidney survival of SLKT recipients compared to solitary kidney transplant (KT) recipients. Method We performed a retrospective analysis of all SLKT recipients performed in a single transplant Center (University Hospital of Modena, Italy) from 01/01/2004 to 12/31/2016. All patients were aged more than 18 years. Results 34 SLKT were performed over 16 years of transplant activity. Mean age of recipients was 51.3 ±9.1years. Males accounted for 65% of the population. All patients were of Caucasians origin except one of African origin. Mean BMI was 69.5 ± 13.9 Kg. Hepatitis C Virus (HCV)-related cirrhosis was the main cause (38.1%) of hepatic failure. Other causes of hepatic disease were ADPKD (26.5%), hepatitis B Virus (HBV) (11.8%), alcohol (8.8%), combined HCV-HBV infection (5.9%), Von Gierke Disease (2.9%), primary biliary cirrhosis (2.9%), and autoimmune cirrhosis (2.9%). Six patients developed hepatocellular carcinoma before undergoing SLKT. Renal disease was caused by ADPKD (26.5%), diabetic nephropathy (14.7%), glomerulonephrites (29.4%), hepatorenal syndrome (8.8%) and other renal diseases (20.6%). Overall, 14.7% of patients was affected by Human Immunodeficiency Virus (HIV), 50% by hypertension and 41% by diabetes. Mean MELD at transplantation was 42 (39.2-46.5) and mean serum creatinine value in pre-emptive patients was 3.09 ±1.4 mg/dl. Mean of donors was 46.7±15.3 years and main cause of death was cranial trauma (47.1%), followed by cerebral haemorrhage (41.2%). Mean KDPI was 52% (22-63) and KDRI 1 (0.73-1.1). Mean time on waiting list was 2.8±1.2 years and half of patients was on dialysis maintenance before SLKT. Mean ischemia time were 6.5 ±1.3 and 12.3 ±2.1 hours for liver and kidney, respectively. Only one patient (2.9%) received double kidney transplantation. Primary induction agent was anti-IL2 receptor monoclonal antibodies (82.6%), thymoglobulin (13%) and with methylprednisolone (4.1%). Post SLKT, kidney early complication consisted of 3 delayed graft functions and 1 transplanctectomy in the only double kidney transplant recipient. At the end of the follow-up (8±4.1 years), mean creatinine was 1.44 ± 0.5 mg/dl and kidney survival accounted for 87.9%. Cox regression analysis showed recipient’ age as a protective factor (HR, 0.03; CI95%, 0.8-0.9) for kidney rejection and donor age as a risk factor (HR, 1.13,CI95% 1-1.1) for renal graft loss. Patient survival at 10 years was 91.2%. Two deaths were caused by infections (50%) and 2 by digestive haemorrhages (50%). SLKT recipients were confronted with 304 cadaveric donor KT recipients performed in the same transplant Center from 01/01/2006 to 12/31/2016. Statistical analysis showed that SLKT recipients had shorter waiting list, dialysis vintage and ischemia times. SLKT recipients had a major prevalence of diabetes and HCV infection but a lower prevalence of hypertension. DGF were less common in SLKT. Patient and graft survival a 1, 5 and 10 years did not show statistically significant differences between SLKT and KT. Conclusion Our analysis shows excellent kidney and patient survival in SLKT. SLKT and KT recipients had similar 1, 5 and 10-years patient and graft survival.

Primary hyperoxaluria type 1 in children: Clinical classification, renal replacement therapy, and outcome in a single centre experience.

Primary hyperoxaluria type 1 (PH1) is a rare disease that is challenged by the overproduced oxalate and commonly presented with radiopaque renal stones or obstructive uropathy. This study aimed to report clinical presentations, renal replacement therapy (RRT), and outcome of PH1 in end stage kidney disease (ESKD) children. This is an observational cohort study. Data of 22 patients with ESKD due to PH1 were analyzed at Pediatric Nephrology Unit, Faculty of Medicine Cairo University. Infantile onset patients (n= 10) had worst renal outcome (80% with ESRD at presentation, p=0.019) and worse patient outcome (mortality 40%, p=0.016) than juvenile (n=9) and late onset (PH1 n=3) patients. RRT modalities include peritoneal dialysis (PD) in 7 (31.8%), hemodialysis (HD) in 11 (50%), and combined liver kidney transplantation (CLKT) in 4 (18.2%) patients. Infectious complications were encountered in 42.8% of PD patients. Better HD adequacy was observed with frequent HD (n=6) and/or HD via arteriovenous fistula (AVF) than with infrequent dialysis (n=5) and/or via central venous line (CVL) (p=0.0001 and 0.0047, respectively). Morbidity and mortality (infection related) rates of the whole cohort were 63.6% and 31.8%, respectively. Clinical presentation of PH1 varies according to the age of onset (infantile onset being the most aggressive form). Aggressive HD (better through AVF) is needed to achieve acceptable HD adequacy, PD was challenged by infection. Infection found to be the main cause of mortality even after successful CLKT.

Candida Contamination in Kidney and Liver Organ Preservation Solution: Does It Matter?

Introduction: Fungal infections remain a major challenge affecting outcomes after kidney (KT) and liver transplantation (LT). Methods: In this retrospective single center study, the incidence of Candida contamination in renal and hepatic graft preservation solution (PS) was evaluated. In addition, Candida associated infections in recipients and related complications were analyzed. Results: Overall, the PS of 1248 hepatic and 1273 renal grafts were evaluated. The incidence of fungal contamination in the PS of hepatic and renal grafts was 1.2% and 0.86%, respectively. Additionally, the hepatic PS of one patient who underwent a combined liver–kidney transplant had Candida contamination. Candida albicans was the most common organism (70.4%) and 65.4% of the patients received antifungal treatment. Candida-associated complications in the recipients was 19%. Complications in LT patients included Candida peritonitis and Candida sepsis. Two KT recipients with contaminated PS developed a mycotic aneurysm at the anastomotic site resulting in severe bleeding. The 1-year mortality in patients with PS contamination for LT and KT recipients was 33% and 18%, respectively. Although the incidence of fungal contamination of PS was low, contaminated PS was associated with a high mortality. Conclusion: The results of the study suggest that PS should be evaluated for fungal growth.

Combined Liver Kidney Transplant in Adult Patient With Alagille Syndrome and Pulmonary Hypertension

In this article, we describe a case of a 33-year-old female with Alagille syndrome complicated by bilateral branch pulmonary artery stenosis resulting in moderate pulmonary hypertension, end-stage liver disease complicated by portal hypertension, and chronic renal disease who presented for combined liver-kidney transplant. Alagille syndrome is an autosomal dominant disease affecting the liver, heart, and kidneys. Multidisciplinary preoperative evaluation was performed with a team consisting of a congenital heart disease cardiologist, a cardiac anesthesiologist, a nephrologist, and a transplant surgeon. We describe Alagille syndrome and our intraoperative management. To our knowledge, this is the first description of a combined liver-kidney transplant in an adult patient with Alagille syndrome.

POS-787 UROLITHIASIS IN KIDNEY TRANSPLANT PATIENTS

De novo or recurrent urolithiasis after kidney transplantation is a rare yet complex kidney transplant (KT) complication. Lithogenesis is favored by multiple medical and surgical factors related to transplantation. Our study aimed to estimate the prevalence of urolithiasis in KT recipients in our department, to identify main causes, and to describe the therapeutic options and evolution. This was a retrospective observational and descriptive study conducted in the nephrology, dialysis and renal transplantation department. We have collected all the KT patients who developed urolithiasis after transplantation. Were ruled out patients who received a donor gifted graft lithiasis. Among 275 KT patients, four cases of urolithiasis were identified. Primary hyperoxaluria type 1 (PH1) was diagnosed in two patients. In the first case, the patient was initially diagnosed with end-stage renal disease and tubulointerstitial nephritis secondary to multiple radiopaque urolithiasis. No specific etiology was found. The genetic testing for the most frequent Tunisian mutations in PH1 was negative. It was until one month after the transplantation when the diagnosis of PH1 was made. The graft biopsy showed calcium oxalate crystal deposition in the kidney. A new genetic test concluded then to a novel mutation named p.Pro28Ser.The second case of PH1 was diagnosed before transplantation. The patient underwent then a combined liver-kidney transplant. Unfortunately, the disease recurred on the graft within 10 months. Both patients lost their graft with return to hemodialysis. The other 2 cases of urolithiasis had no history of lithiasis preceding the transplantation. One of them, presented 9 months after an obstructive acute graft injury with a fungus ball, radiopaque lithiasis at the inferior, and the median calyx. The etiological assessment was negative. He was kept under regular ultrasound, clinical, and biological monitoring. No complications occurred. The last patient had a spontaneous elimination of his inferior calyceal calculus. Our study confirms the rarity of urolithiasis in KT recipients. PH1 was the most common cause that posed a therapeutic challenge.

Combined liver kidney transplantation for primary hyperoxaluria type 1: Will there still be a future? Current transplantation strategies and monocentric experience.

Combined liver-kidney transplantation is a therapeutic option for children affected by type 1 primary hyperoxaluria. Persistently high plasma oxalate levels may lead to kidney graft failure. It is debated whether pre-emptive liver transplantation, followed by kidney transplantation, might be a better strategy to reduce kidney graft loss. Our experience of 6 pediatric combined liver-kidney transplants for primary hyperoxaluria type 1 in pediatric recipients was retrospectively analyzed. Plasma oxalate levels were monitored before and after transplantation. All the recipients were on hemodialysis at transplantation. Median [IQR] recipient's age at transplantation was 11 [1-14]years; in all cases, a compatible graft from a pediatric brain-dead donor aged 8 [2-16]years was used. In a median follow-up of 7 [2-19]years after combined liver-kidney transplantation, no child died and no liver graft failure was observed; three kidney grafts were lost, due to chronic rejection, primary non-function, and early renal oxalate accumulation. Liver and kidney graft survival remained stable at 1, 3, and 5years, at 100% and 85%, respectively. Kidney graft loss was the major complication in our series. Risk is higher with very young, low-weight donors. The impact of treatment with glyoxalate pathway enzyme inhibitors treatment in children with advanced disease as well as of donor kidney preservation by ex vivo machine perfusion needs to be evaluated. At present, a case-by-case discussion is needed to establish an optimal treatment strategy.

Isolated Liver Rejection After Lung and Combined Kidney-Liver Transplantation: A Case Report

Liver allografts are unique in solid organ transplantation as they are less susceptible to both acute and chronic rejection. Operational tolerance, defined as prolonged graft survival in the absence of immunosuppression, is also achieved more frequently with liver allografts. It is unknown if the presence of multiple allografts in the same individual, levels of immunosuppression, or the presence of cystic fibrosis (CF) impacts the livers ability to ward off rejection or achieve operational tolerance. We describe an unsensitized, ABO-compatible patient with CF who underwent double lung transplantation and several years later a combined liver-kidney transplant. He developed isolated late acute T-cell mediated rejection of his liver allograft despite a high level of immunosuppression (IS) required for his lung and kidney allografts. To our knowledge, this is the first case of isolated liver rejection in a patient with 3 separate organ allografts, or in a patient with CF, to be reported in the literature. This isolated liver rejection is out of keeping with typically accepted ideas about orthotopic liver tolerance.

Delayed kidney transplantation in combined liver-kidney transplantation.

To review the impact of delayed kidney transplantation approach in combined (simultaneous) liver-kidney transplantation (CLKT). CLKT offers a life-saving procedure for patients with both end-stage liver disease and chronic kidney disease or prolonged acute kidney injury. It is the most common multiorgan transplant procedure in the US accounting for 9-10% of all liver transplants performed. The number of CLKT has also been increasing in other countries with a better understanding of hepato-renal syndrome. US is the only country which implemented a national allocation policy for CLKT in 2017. Due to the different physiological needs of liver and kidney allografts immediately after transplantation, delayed kidney transplantation approach in CLKT has been introduced for the first time by the Indiana Group, naming it as 'the Indiana Approach'. Over the years, many other groups in the US and in Europe published better outcomes in CLKT using the delayed kidney transplantation approach with the support of hypothermic machine perfusion. Several groups have shown that delayed kidney transplantation in CLKT is a safe procedure with better outcomes in graft(s) and patient survival.

Normothermic Machine Preservation of Marginal Livers in Australasia - Initial Brisbane Experience Using a “Back-to-Base” Approach

Introduction: The assessment of marginal liver suitability using empirical criteria remains imprecise. Ex-vivo normothermic machine perfusion (NMP) allows for a period of graft assessment under near-physiological conditions, which might improve the selection of such livers for transplantation. We describe the first 11 clinical applications of NMP in Australasia using a “back-to-base” approach. Methods: Eleven marginal livers were accepted for preservation and assessment on the OrganOx metra device following a period of static cold storage (post-SCS-NMP). Average donor risk index was 1.53 (1.08-1.93), with five grafts donated after brain death (DBD) and six donated after circulatory death (DCD). All DCD grafts were outside of established local criteria. Average cold ischaemic time and NMP time was 5.2 (4.2-6.5) hours and 12.0 (9.1-17.6) hours respectively. Recipient MELD score was 17 (11-20), including one combined liver-kidney transplant and one re-transplant. Results: All livers met pre-established viability criteria and were successfully transplanted. Five (45%) recipients developed early allograft dysfunction based solely on peak AST >2000 U/L (average 1860 (629-8910) U/L, Figure 1). Two patients (18%) required revisional surgery for biliary anastomotic complications following initial Roux-en-Y hepaticojejunostomy. No clinically significant biliary problems were observed in the nine patients receiving duct-to-duct anastomosis. All cases have satisfactory graft function to date. Conclusions: Post-SCS NMP was successfully implemented in 11 cases, enabling the safe utilisation of grafts deemed non-transplantable using static cold storage preservation alone. The technique was user friendly, improved transplant logistics and surgeon confidence, and increased local transplant activity by 10%.

Long Term Outcomes of Combined Liver Kidney Transplantation in Children with Heritable Disorders

Introduction: Outcomes of combined liver kidney transplantation in children remains a largely unquantified yet potentially life transforming procedure for those with heritable disease. No case series assessing the impact of the CLK on patient outcome for children solely with heritable disease is available. We therefore sought to retrospectively analyse the practice in a large London quaternary centre. Methods: Children undergoing liver kidney transplantation from 2003 onwards were analysed. Indication for transplant graft types, graft survival and patient survival were recorded. Disease specific metabolic parameters were also recorded. Results: 9 children underwent liver kidney transplanation of which 7/9 were combined. All grafts in CLK group were deceased donor (1 whole liver, 1right lobe, 5 left lateral segments). The mean age was 6.8 yrs. The indication was primary type 1 hyperoxaluria (n=1), Allagile (n=1) and autosomal recessive polycystic kidney disease (n=5). The median follow up was 5213 days. 1 year and 5 year liver and kidney graft survival was 100%. Mean GFR at one year was 66.6 mls/min and last follow up was 64.4mls/min. Mean AST level at last follow up was 44. One child required re transplant at five years due to chronic liver graft rejection. All current transplant grafts were functional at last follow up. Conclusions: CLK is a safe practice in children with heritable and metabolic conditions. Excellent graft outcomes are possible. In countries where deceased donor organ pools are readily available this practice should be adopted as the mainstream of treatment.

Acute Kidney Injury Following Pediatric Liver Transplant.

To determine the incidence, severity, and risk factors of postoperative acute kidney injury in pediatric liver transplant patients with and without inborn errors of metabolism. Retrospective cohort study. Single-center PICU. All children less than or equal to 18 years old who received a liver transplant between January 2009 and July 2019. None. Following exclusion criteria there were 92 transplant encounters. After excluding patients who received combined kidney-liver transplantation, acute kidney injury occurred in 57% of patients (N = 49), with 25.6% (N = 22) stage 1, 15.1% (N = 13) stage 2, and 16.3% (N = 14) stage 3. In an adjusted analysis, metabolic indication for transplant was not significantly associated with presence of acute kidney injury (p = 0.45). For the subset of patients without inborn errors of metabolism, the odds of having acute kidney injury was 1.50 (95% CI: 1.00-2.26) for each 1-unit increase in preoperative INR after adjusting for the covariates of age, preoperative albumin, CMV status of donor, and preoperative creatinine. In the full cohort, as well as the sample of children without inborn errors of metabolism, presence of acute kidney injury was associated with longer total hospital stay as well as number of ICU days. Acute kidney injury in the early postoperative period is common in pediatric liver transplant patients (57%), 31.4% of whom had severe disease. In patients without inborn errors of metabolism, each unit increase in preoperative INR suggests a higher risk of acute kidney injury after adjusting for covariates including preoperative creatinine. This finding suggests an association between the severity of preoperative synthetic liver function and the risk of developing postoperative acute kidney injury which requires further investigation.

PDB40 An EARLY Cost-Utility MODEL of Mrna-Based Therapies Compared with Standard of Care in EARLY-Onset Methylmalonic Acidaemia in the United Kingdom

Methylmalonic acidaemia (MMA) is a rare metabolic disease with high mortality rates and severe chronic sequelae in children surviving the initial disease onset. Current standard of care (SOC) includes low-protein diet, pharmacologic therapy and, potentially, liver transplantation or combined liver-kidney transplantation. Also, innovative intracellular mRNA-based therapies are currently being trialled that could offer novel systemic treatment. The objective of this study was to build an early cost-utility model to identify key variables impacting the cost-utility of mRNA-based therapies versus SOC in early-onset MMA in the United Kingdom (UK). A Markov model simulating a hypothetical cohort of newborn MMA patients was developed from the UK healthcare system perspective. Efficacy and cost inputs were obtained from the literature, British National Formulary and NHS Reference Costs. Quality-adjusted life years (QALYs) and costs were estimated for each treatment arm over a lifetime horizon, with a discount rate of 3.5% for both. One- and two-way sensitivity analyses were conducted to identify key model drivers, such as those with largest impact on the incremental cost-effectiveness ratio (ICER). When comparing mRNA-based therapies with diet-based management, the variables with the largest impact on the ICER were the annual cost of mRNA-based therapy, improvement in utility following mRNA-based therapy, patient weight, cost of medical foods and cost of L-carnitine in that order. Results were similar when comparing mRNA-based therapies with the diet/transplant arm. Despite the current lack of a strong evidence base, this model can be used to estimate value-based prices of mRNA-based therapies in MMA and guide the design of evidence generation activities.