Combined Liver-kidney Transplantation Research Articles

Human glyoxylate metabolism revisited: New insights pointing to multi-organ involvement with implications for siRNA-based therapies in primary hyperoxaluria.

Glyoxylate is a toxic metabolite because of its rapid conversion into oxalate, as catalyzed by the ubiquitous enzyme lactate dehydrogenase. This requires the presence of efficient glyoxylate detoxification systems in multiple subcellular compartments, as glyoxylate is produced in peroxisomes, mitochondria, and the cytosol. Alanine glyoxylate aminotransferase (AGT) and glyoxylate reductase/hydroxypyruvate reductase (GRHPR) are the key enzymes involved in glyoxylate detoxification. Bi-allelic mutations in the genes coding for these enzymes cause primary hyperoxaluria type 1 (PH1) and 2 (PH2), respectively. Glyoxylate is derived from various sources, including 4-hydroxyproline, which is degraded in mitochondria, generating pyruvate and glyoxylate, as catalyzed by the mitochondrial enzyme 4-hydroxy-2-oxoglutarate aldolase (HOGA); however, counterintuitively, a defect in HOGA1 is the molecular basis of primary hyperoxaluria type 3 (PH3). Irrespective of its underlying cause, hyperoxaluria in humans leads to nephrocalcinosis, recurrent urolithiasis, and kidney damage, which may culminate in kidney failure requiring combined liver-kidney transplantation in severely affected patients. In the past few years, therapeutic options, especially for primary hyperoxaluria type 1 (PH1), have greatly been improved thanks to the introduction of two RNAi-based therapies that inhibit either the production of glycolate oxidase (lumasiran) or lactate dehydrogenase (nedosiran). While lumasiran only targets PH1 patients, nedosiran was specifically developed to target all three subtypes of PH. Inspired by the findings reported in the literature that nedosiran effectively reduced urinary oxalate excretion in PH1 patients but not in PH2 or PH3 patients, we have now revisited glyoxylate metabolism in humans and performed a thorough literature study which revealed that glyoxylate/oxalate metabolism is not confined to the liver but instead involves multiple different organs. This new view on glyoxylate/oxalate metabolism in humans may well explain the disappointing results of nedosiran in PH2 and PH3, and provides new clues for the future generation of new therapeutic strategies for PH2 and PH3.

Perioperative and Long-Term Outcomes After Combined Liver and Kidney Transplantation: A Single-Center Experience.

Combined liver-kidney transplantation (CLKT) has evolved as a therapeutic option for patients with concurrent end-stage liver and renal diseases. This study evaluates the perioperative and long-term outcomes of CLKT at a single center in Slovenia, highlighting the challenges and successes of simultaneous organ transplantation. We retrospectively analyzed all patients undergoing simultaneous CLKT at the University Medical Centre Ljubljana from April 2014 to June 2023. Data on demographics, cause of liver and kidney disease, operative details, postoperative complications, patient and graft survival, and follow-up were collected and analyzed. Five patients aged 27 to 60 years underwent CLKT within the study period. All transplants involved deceased donors with whole-liver grafts. Indications for CLKT were polycystic liver disease (n = 3), Caroli's disease (n = 1), and alcoholic cirrhosis (n = 1). The mean follow-up duration was 45.2 months, with a 100% survival rate. The incidence of surgical and postoperative complications was low. This pioneering series of simultaneous CLKTs in Slovenia demonstrates the feasibility and effectiveness of the procedure in smaller transplant centers. Despite challenges, including T cell-mediated kidney rejection and surgical complications, the study emphasizes the importance of comprehensive postoperative care and management in optimizing outcomes for CLKT recipients.

Combined Liver-Kidney Transplant in Children

Combined Liver-Kidney Transplant in Children

Islet-after-kidney transplantation versus kidney alone in kidney transplant recipients with type 1 diabetes (KAIAK): a population-based target trial emulation in France

Islet transplantation has been associated with better metabolic control and quality of life than insulin treatment alone, but direct evidence of its effect on hard clinical endpoints is scarce. We aimed to assess the effect of islet transplantation on patient-graft survival in kidney transplant recipients with type 1 diabetes. In this retrospective cohort study, we enrolled all patients with type 1 diabetes who received a kidney graft in France during the study period, identified from the CRISTAL nationwide registry. Non-inclusion criteria included recipients from transplant centres that never proposed islet transplantation during the study period, recipients with a functional pancreas throughout the follow-up duration, recipients with more than two kidney transplants, HLA-sensitised recipients, recipients with less than 1 year of follow-up after kidney transplantation, misclassified recipients with type 2 diabetes, recipients aged over 65 years, recipients of kidney grafts from Donation after Circulatory Death donors, recipient with HIV or hepatitis, recipients with cancer, and recipients of combined liver-kidney transplants. Patients who also received islet-after-kidney (IAK) transplantation were compared with controls who received kidney transplantation alone according to a 1:2 matching method based on time-dependent propensity scores, ensuring patients comparability at the time of islet transplantation. The primary outcome was patient-graft survival, a composite outcome defined by death, re-transplantation, or return to dialysis. Between Jan 1, 2000, and Dec 31, 2017, 2391 patients with type 1 diabetes were identified as having received a kidney transplant, 47 patients of whom also received an islet transplantation. 2002 patients were not eligible for islet transplantation and 62 were excluded due to missing data. 327 eligible recipients from 15 centres were included in the study dataset for the target trial emulation. 40 patients who received IAK transplantation were successfully matched to 80 patients who received kidney transplantation alone. 13 (33%) of 40 patients in the IAK transplantation group returned to dialysis or died, compared with 36 (45%) of 80 patients in the kidney transplantation alone group. We found a significant benefit of islet transplantation compared with kidney transplantation alone on patient-graft survival, with a hazard ratio (HR) of 0·44 (95% CI 0·23-0·88; p=0·022), mainly explained by a protective effect on the risk of death (HR 0·41, 0·13-0·91; p=0·042). There was no meaningful association between IAK and death-censored graft survival (0·73, 0·30-1·89; p=0·36). In kidney transplant recipients with type 1 diabetes, IAK transplantation was associated with a significantly better patient-graft survival compared with kidney transplantation alone, mainly due to a protective effect on the risk of death. These results potentially serve as compelling grounds for advocating wider access to islet transplantation in patients with type 1 diabetes undergoing kidney transplant, as reimbursement of islet transplantation is provided in few countries worldwide. Programme Hospitalier de la Recherche Clinique, Fondation pour la Recherche Medicale, and Fonds de Dotation Line Renaud-Loulou Gasté.

P.424: Kidney transplantation vs. combined liver-kidney transplantation - outcomes of kidney function in autosomal dominant polycystic kidney disease.

P.424: Kidney transplantation vs. combined liver-kidney transplantation - outcomes of kidney function in autosomal dominant polycystic kidney disease.

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.

Histopathologic Perspective of Combined Liver–kidney Transplant: In Primary Hyperoxaluria Type 1 Patient

Abstract Primary hyperoxaluria (PH) type 1 is a rare autosomal recessive disorder of glyoxylate metabolism. Its prevalence is 1–3 cases/million people. Glyoxylate is the precursor of oxalate which is believed to be produced by oxidation in liver peroxisomes. Serine-pyruvate aminotransferase/alanine-glyoxylate aminotransferase is an enzyme involved in the metabolism of glyoxylate. In the absence of this enzyme, oxalate and glycolate are overproduced leading to hyperoxaluria. This causes urolithiasis or nephrocalcinosis, which are conditions caused by the deposition of calcium oxalate. Due to its rarity and heterogeneous phenotype, it remains unrecognized due to which diagnosis is delayed, ending up in end-stage renal disease (ESRD) and ultimately death. Hence, early diagnosis and simultaneous hepatorenal transplant remain the mainstay to avoid systemic oxalosis. Here, we discuss a case of a 43-year-old female who underwent combined liver–kidney transplant with a history of multiple episodes of renal calculi since childhood ultimately landing into ESRD in view of PH type 1.

Hernia Correction After Liver Transplantation Using Nonvascularized Fascia.

Liver transplantation is an increasingly frequent surgical procedure, with elevated rates of postoperative incisional hernias ranging from 5% to 46%. There are numerous known risk factors for incisional hernia, including the type of incision, patient sex, and presence of comorbidities such as diabetes, ascites, older age, and the use of steroids. Most studies on the treatment of incisional hernias in patients who have undergone liver transplantation have shown consistently high rates of complications. Consequently, we propose the use of nonvascular fascia for the symptomatic treatment of incisional hernias in patients with concomitant liver transplantation. We performed our new technique on 8 patients, who had previously undergone liver transplantation, between January 2019 and January 2023. The patients were examined using imaging techniques during the follow-up period. Of the 8 patients, 7 were liver transplant recipients and 1 was a combined liver-kidney transplant patient. The median donor age was 57 y (5-66 y), whereas the mean recipient age was 58 y (31-66 y). The median patient height and weight were 163 cm (117-185 cm) and 76 kg (17-104 kg), respectively. Immunosuppression did not change in fascia recipients. The median time between transplantation and hernia repair surgery was 41 mo (5-116 mo). The sizes of the aponeurotic defects varied from 6 × 6 to 25 × 20 cm. Two patients experienced complications: one experienced bulging that required reintervention and the other experienced surgical site seroma. There was no mortality related to the use of the technique, and none were reported during follow-up. With its promising results, nonvascularized fascial transplantation can be a successful treatment for incisional hernias in patients who had previously received a liver transplant.

#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