Simultaneous Transplantation Research Articles

Challenges in Beta Cell Replacement for Type 1 Diabetes.

Type 1 diabetes (T1D) presents a significant global health challenge, characterized by immune-mediated destruction of pancreatic beta-cells. Achieving therapeutic goals such as prevention of immune destruction, preservation of beta-cell mass, and automated insulin delivery remains complex due to the disease's heterogeneity. This review explores the advancements and challenges in beta-cell replacement therapies, including pancreas and islet cell transplantation, stem cell-derived β-cell generation, and biotechnological innovations. Pancreas transplantation, especially simultaneous pancreas and kidney transplantation (SPK), has evolved significantly, offering insulin independence and improved quality of life despite surgical and immunological complications. Allogeneic islet transplantation, though less invasive, faces challenges such as donor scarcity, immunosuppressive therapy, and variable long-term success. Innovations in stem cell therapy, particularly using human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), promise an unlimited source of β-cells. However, translating these advances into clinical applications involves overcoming technical, biological, and ethical hurdles. Strategies such as immunomodulation, encapsulation, and genetic engineering are critical to enhancing the viability and integration of transplanted cells. This review provides a comprehensive overview of the scientific intricacies and potential of β-cell replacement therapies, emphasizing the need for continued research to address the remaining challenges and improve diabetes care outcomes.

Safety and efficacy of simultaneous liver transplantation and sleeve gastrectomy in morbid obese end-stage liver disease patients: The LT-SG study.

In obese patients, metabolic dysfunction-associated steatotic liver disease is becoming a leading aetiology of end-stage liver disease and hepatocellular carcinoma. Simultaneous liver transplantation and sleeve gastrectomy (LT-SG) has been proposed in the US, but the safety and efficacy of the procedure have not been widely explored in Europe. Between January 2016 and December 2022, morbidly obese patients listed for LT at Tor Vergata University were enrolled in the LT-SG study. Primary outcomes were: i) safety expressed as 30- and 90-days overall survival (OS) and ii) major postoperative complications (Clavien-Dindo > IIIa). The secondary outcome was efficacy expressed as a 3-year %excess BMI loss(%EBMIL). Eleven patients were enrolled in the study. The median BMI at transplantation was 42 (IQR 38-48). Indications to LT-SG were HCC (63.6%) and cirrhosis (36.4%). In 54% of cases, donors had high-risk characteristics (ET-DRI>1.6). The 30 and 90-day OS were 63.6% and 54.5%, respectively. All deaths occurred in patients with p-SOFT>15 or in patients who had at least three of the following characteristics: >60 years, BMI >45, metabolic syndrome, MELD>25 or ET-DRI >1.6. The six months, 1, 2 and 3 years %excess BMI loss was 73%, 60%, 50% and 43%, respectively. LT-SG is a complex procedure thatmay carry excess risk in an unselected population. It should be considered only in highly selected patients. Standard donors are recommended and prioritization of severely obese patients on the waiting list should be considered.

Perfusion Computed Tomography for Assessing Pancreas Graft Volumetric Perfusion After Simultaneous Pancreas and Kidney Transplantation.

Background: There is paucity of data in the available medical literature regarding the parameters of the volumetric perfusion of pancreas grafts. Methods: From 5 February 2016 to 23 December 2021, we performed perfusion computed tomography in 41 patients at different times after simultaneous pancreas and kidney transplantation. The study group consisted of 18 men (44%) and 23 women (56%) with a long history of type 1 diabetes mellitus complicated by terminal chronic renal failure. The results of the perfusion computed tomography of the pancreas graft were studied, and the effects of post-transplantation timing and graft revascularization peculiarities on volumetric perfusion parameters were evaluated. Results: The median arterial blood flow, arterial blood volume, and permeability of the pancreas graft were 115.1 [99.7;130.3] mL/100 mL/min, 46.7 [37.4;56.9] mL/min, and 8.6 [4.1;11.4] mL/100 mL/min, respectively. No statistically significant differences in the averaged perfusion values were found in the head, body, and tail of the pancreas graft. The post-transplantation timing and the number of arteries involved in graft revascularization did not have a significant effect on the volumetric perfusion of the graft. Conclusion: The volumetric perfusion results of the pancreas graft correspond to those obtained in the study of pancreatic perfusion in healthy participants.

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.

Simultaneous or sequential kidney-liver transplantation in primary hyperoxaluria.

Primary hyperoxaluria type 1 is responsible for pediatric kidney failure in 1 to 2% of cases. Novel therapies based on RNA interference are changing the natural history of the disease. However, for those who do progress to kidney failure, and for patients living in countries that cannot afford these expensive therapies, liver-kidney transplantation may remain the only efficient therapy. The aim of the study was to evaluate the outcome of patients with primary hyperoxaluria type 1 who received simultaneous or sequential liver-kidney transplantation. We retrospectively evaluated 10 patients, five of whom received a simultaneous transplantation, and five underwent sequential transplantation, with a median postponement of the kidney transplantation of 8months (range 4-20). Among the patients, 5 were from medium-lowincome countries. Median follow up was 3.2years (range 1.6-11). Median estimated glomerular filtration rate at 6 and 12months was 81.2 (range: 45.7-108.8) and 79.3ml/min/1.73m2 (range 54.7-112.1) in patients who underwent simultaneous transplantation, and 45.7 (range 34.5-86.7) and 38.3ml/min/1.73m2 (range 29.9-77.5) in those with sequential transplantation (p:NS). Biopsies performed at 6 and 12months showed precipitation of calcium oxalate crystals in 7 patients, demonstrating the recurrence of deposition despite the delay between liver and kidney transplantation. No differences in kidney function or in post-transplant renal oxalate precipitation were observed between patients that underwent bilateral nephrectomy and those who did not. As of their most recent follow up, none of the patients has lost their kidney graft. Our study shows that by adapting the transplant strategy to individual cases, patients with primary hyperoxaluria type 1 can be successfully treated.

The TEG 6s Global Hemostasis System is Useful for Coagulation Management in Simultaneous Pancreas and Kidney Transplantation: The First Two Cases

Introduction: Hypercoagulability-related graft thrombosis is the leading cause of graft failure after simultaneous pancreas-kidney transplantation (SPK). Addressing this issue is crucial to improve the outcomes of SPK recipients. Thromboelastography (TEG) has been used to assess the coagulation profiles of SPK recipients. Recently, a new-generation TEG device, the TEG 6s Global Hemostasis System, was introduced. This device offers advantages over TEG 5000, including less frequent calibration requirements, ease of use, and reduced sensitivity to movement. We hypothesized that TEG 6s would enhance coagulation management in SPK. Methods: We report two cases of Asian female SPK recipients in whom TEG 6s was used to assess coagulation status at six preset times during and after surgery. Results: Preoperatively, both patients exhibited hypercoagulability on TEG 6s. Postoperative intravenous heparin was administered, and the dose was titrated based on the TEG 6s results. Vascular thrombosis was not observed in either patient. Detailed TEG 6s and standard laboratory test results are reported. This pilot study demonstrates that TEG 6s monitoring can effectively assess coagulation status in SPK recipients, aiding in optimal coagulation management and reducing the risk of thrombotic complications leading to graft loss. The TEG 6s facilitated real-time and accurate coagulation assessment, allowing for tailored anticoagulant therapy. Conclusions: This is the first observational study to use TEG 6s in SPK recipients, indicating its potential benefits in improving patient outcomes. Further studies with larger sample sizes are warranted to validate these findings and establish comprehensive guidelines for using TEG 6s in SPK procedures.

Simultaneous Heart-Kidney Transplant Is the Best Treatment Option for Patients with CKD and ESKD vs. Heart Transplant Alone

Simultaneous Heart-Kidney Transplant Is the Best Treatment Option for Patients with CKD and ESKD vs. Heart Transplant Alone

Comparative Analysis of Infection and Rejection Rates for Recipients of Kidney-after-Liver (KALT) Compared with Simultaneous Liver and Kidney Transplant (SLK)

Comparative Analysis of Infection and Rejection Rates for Recipients of Kidney-after-Liver (KALT) Compared with Simultaneous Liver and Kidney Transplant (SLK)

Influence of Recipient Education on the Outcome of Simultaneous Pancreas and Kidney Transplantation

Influence of Recipient Education on the Outcome of Simultaneous Pancreas and Kidney Transplantation

Investigation of Proteinuria in a Simultaneous Heart-Kidney Transplant Recipient with AL Amyloidosis

Investigation of Proteinuria in a Simultaneous Heart-Kidney Transplant Recipient with AL Amyloidosis

Subclinical Pancreas Rejection on Protocol Biopsy Within the First Year of Simultaneous Pancreas Kidney Transplant.

This single-center retrospective study investigated subclinical rejection prevalence and significance in simultaneous pancreas and kidney transplant (SPKT) recipients. We analyzed 352 SPKT recipients from July 2003 to April 2022. Our protocol included pancreas allograft surveillance biopsies at 1, 4, and 12months post-transplant. After excluding 153 patients unable to undergo pancreas biopsy, our study cohort comprised 199 recipients. Among the 199 patients with protocol pancreas biopsies, 107 had multiple protocol pancreas biopsies in the first year, totaling 323. Subclinical rejection was identified in 132 episodes (41%). Of these, 72% were Grade 1, 20% were indeterminate, and 8% were Banff Grade 2 or higher. All episodes of subclinical rejection were treated. Rates of pancreas graft loss (10%vs. 7%) and clinical rejection (21%vs. 20%) at 3 years were similar between those with and without subclinical rejection. Subclinical rejection Banff Grade 2 or more was associated with poor pancreas graft survival HR of 5.5 (95% CI: 1.24-24.37, p = 0.025). Of 236 simultaneous protocol kidney and pancreas biopsies, 102 (43%) showed pancreas subclinical rejection, while only 17% had concurrent kidney subclinical rejection. Our findings suggest limited predictive value of pancreatic enzymes and euglycemia in detecting pancreas rejection. Furthermore, poor concordance existed between pancreas and kidney subclinical rejection.

Pretransplant Hypoalbuminemia Is Not Associated with Worse Outcomes among Simultaneous Pancreas and Kidney Transplant Recipients

Pretransplant Hypoalbuminemia Is Not Associated with Worse Outcomes among Simultaneous Pancreas and Kidney Transplant Recipients

Decreased Risk for Rejection in Simultaneous Heart-Kidney Transplant

Decreased Risk for Rejection in Simultaneous Heart-Kidney Transplant

Prospective evaluation of cystatin C in the assessment of kidney dysfunction and survival in liver transplant candidates.

Kidney dysfunction is associated with decreased survival in liver transplant (LT) candidates, yet serum creatinine (sCr) is a poor surrogate for glomerular filtration rate (GFR) in this population. Serum cystatin C (CysC) may provide a more accurate assessment of kidney function and predict outcomes. We performed a multicenter prospective cohort study of consecutive candidates for LT. CysC was obtained at LT evaluation (n = 244), and a subset underwent simultaneous I 125 -iothalamate clearance for measured GFR (mGFR) assessment (n = 137). Patients were followed to assess the need for pre-LT renal replacement therapy, simultaneous liver and kidney transplant, and survival. Estimated GFR (eGFR) based on MDRD-4, GRAIL, Royal Free Hospital Cirrhosis GFR, and the CKD-EPI equations was assessed for bias, precision, and accuracy in reference to mGFR. Receiver operator characteristic (AUROC) and competing risk survival analyses were performed. CysC more accurately discriminated mGFR than sCr at thresholds of ≤60 and ≤30mL/min/1.73m 2 with AUROC 0.92 ( p = 0.005) and 0.96 ( p =0.01), respectively. All eGFR equations overestimated GFR, especially among females ( p < 0.05). The GRAIL equation demonstrated the least bias, while CKD-EPI-cystatin C was associated with the greatest precision and lowest frequency of GFR overestimation. Among 165 recipients of LT, CysC discriminated pre-LT renal replacement therapy and the need for simultaneous liver and kidney transplant with AUROC of 0.70 and 0.85, respectively. Cumulative incidence of death, accounting for LT as a competing event, increased with CysC ( p = 0.002) but was not observed with sCr overall or among subgroups ( p = NS). CysC more accurately predicts thresholds of mGFR than sCr in candidates for LT. Elevated CysC discriminates pre-LT renal replacement therapy and simultaneous liver and kidney transplant and is strongly associated with survival in contrast with sCr. CysC is a promising tool to improve prognostication among candidates for LT.

The First Case of Intra-portal Islet Implantation During Liver Machine Perfusion Allowing Simultaneous Islet-liver Transplantation in A Human: A New and Safe Treatment for End-stage Liver Disease Combined With Diabetes Mellitus.

Evaluating the safety and efficacy of implanting a liver with islet grafts into patients with end-stage liver disease and diabetes mellitus (DM). DM and end-stage liver diseases are significant health concern worldwide, often coexisting and mutually influencing each other. Addressing both diseases simultaneously is paramount. We utilized the islet transplantation combined ischemia-free liver transplantation (ITIFLT) technique to treat a patient with hepatocellular carcinoma (HCC) and type 2 diabetes mellitus (T2DM). The liver was procured and preserved using the ischemia-free liver transplantation (IFLT) technique, and during normothermic machine perfusion (NMP), isolated and purified islet grafts were transplanted into the liver through the portal vein. Finally, the liver, incorporating with the transplant islet grafts, was implanted into the recipient without interruption of blood supply. The patient received both liver and islet graft from the same donor. The patient achieved insulin-independence by post-transplant day (PTD) 9, and both liver and islet function remained robust. The patient was discharged on PTD 18 and experienced no surgical or transplantation-related complications during the follow-up period. Furthermore, islet grafts presence was observed in liver biopsies after islet transplantation. This landmark case marks the inaugural application of ITIFLT in humans, signifying its potential as a promising treatment modality for end-stage liver disease with DM.

Small Donors, Big Impact: Optimizing Organ Utilization in Simultaneous Pancreas and Kidney Transplantation From Extra Small Pediatric Donors.

Simultaneous pancreas-kidney transplantation (SPK) is the preferred treatment for individuals with type-1 diabetes and end-stage renal disease. However, a limited supply of "Ideal Pancreas Donors" contributed to a growing disparity between available organs and recipients. Even though SPK outcomes from pediatric donors match those from adult donors, unclear guidelines on minimum age and weight criteria for extra small pediatric pancreas donors lead to hesitancy among several transplant centers to utilize these grafts due to concerns about inadequate islet mass, technical challenges, and increased risk of allograft thrombosis. This report details the successful outcomes of SPK transplantations performed at the study center between December 2021 and January 2024, using four extra small pediatric brain-dead donors (ESPDs). Each donor was aged ≤5 years and weighed <20kg. All SPK recipients achieved immediate posttransplant euglycemia without requiring insulin. None of the recipients experienced graft pancreatitis, graft thrombosis, allograft rejection, or required re-exploration. During a 5-27-month follow-up period, all ESPD recipients maintained optimal graft function, as evidenced by normal glucose tolerance tests and HbA1c (4.9%-5.2%), with 100% graft and patient survival. This report examines the usage of ESPDs in SPK transplantation, highlighting their potential to expand the donor pool and reduce wait times in areas with scarce deceased organ donations, thereby increasing the number of available organs for transplantation with acceptable outcomes. Revising donor selection guidelines to reflect the diverse risk-benefit profiles of waitlisted individuals is crucial to addressing geographical disparities and reducing organ discard rates.

325.5: Systemic improvements in a single-center simultaneous pancreas and kidney transplant program.

325.5: Systemic improvements in a single-center simultaneous pancreas and kidney transplant program.

P.482: Advantages of simultaneous kidney and pancreas transplantation in selected patients with type 2 Diabetes Mellitus: A single-center study.

P.482: Advantages of simultaneous kidney and pancreas transplantation in selected patients with type 2 Diabetes Mellitus: A single-center study.

325.9: Donor-derived cell-free DNA (dd-cfDNA) kinetics during rejection and quiescence after simultaneous pancreas and kidney transplant.

325.9: Donor-derived cell-free DNA (dd-cfDNA) kinetics during rejection and quiescence after simultaneous pancreas and kidney transplant.

325.1: Comparison of survival advantage of simultaneous kidney-pancreas vs kidney transplant in patients with diabetes who received mate kidneys.

325.1: Comparison of survival advantage of simultaneous kidney-pancreas vs kidney transplant in patients with diabetes who received mate kidneys.