Browse
Submit Data
Databases
API
Help

Dataset Information

16 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The impact of islet mass, number of transplants, and time between transplants on graft function in a national islet transplant program.

ABSTRACT: The UK islet allotransplant program is nationally funded to deliver one or two transplants over 12 months to individuals with type 1 diabetes and recurrent severe hypoglycemia. Analyses were undertaken 10 years after program inception to evaluate associations between transplanted mass; single versus two transplants; time between two transplants and graft survival (stimulated C-peptide >50 pmol/L) and function. In total, 84 islet transplant recipients were studied. Uninterrupted graft survival over 12 months was attained in 23 (68%) single and 47 (94%) (p = .002) two transplant recipients (separated by [median (IQR)] 6 (3-8) months). 64% recipients of one or two transplants with uninterrupted function at 12 months sustained graft function at 6 years. Total transplanted mass was associated with Mixed Meal Tolerance Test stimulated C-peptide at 12 months (p < .01). Despite 1.9-fold greater transplanted mass in recipients of two versus one islet infusion (12 218 [9291-15 417] vs. 6442 [5156-7639] IEQ/kg; p < .0001), stimulated C-peptide was not significantly higher. Shorter time between transplants was associated with greater insulin dose reduction at 12 months (beta -0.35; p = .02). Graft survival over the first 12 months was greater in recipients of two versus one islet transplant in the UK program, although function at 1 and 6 years was comparable. Minimizing the interval between 2 islet infusions may maximize cumulative impact on graft function.

SUBMITTER: Forbes S

PROVIDER: S-EPMC9292186 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Planning for Uncertainty and Fallbacks Can Increase the Number of Transplants in a Kidney-Paired Donation Program.

Project description:A kidney-paired donation (KPD) pool consists of transplant candidates and their incompatible donors, along with nondirected donors (NDDs). In a match run, exchanges are arranged among pairs in the pool via cycles, as well as chains created from NDDs. A problem of importance is how to arrange cycles and chains to optimize the number of transplants. We outline and examine, through example and by simulation, four schemes for selecting potential matches in a realistic model of a KPD system; proposed schemes take account of probabilities that chosen transplants may not be completed as well as allowing for contingency plans when the optimal solution fails. Using data on candidate/donor pairs and NDDs from the Alliance for Paired Donation, the simulations extend over 8 match runs, with 30 pairs and 1 NDD added between each run. Schemes that incorporate uncertainties and fallbacks into the selection process yield substantially more transplants on average, increasing the number of transplants by as much as 40% compared to a standard selection scheme. The gain depends on the degree of uncertainty in the system. The proposed approaches can be easily implemented and provide substantial advantages over current KPD matching algorithms.

| S-EPMC5559873 | biostudies-literature

Transplant Onconephrology in Patients With Kidney Transplants.

Project description:Cancer is a leading cause of death in patients with kidney transplantation. Patients with kidney transplants are 10- to 200-times more likely to develop cancers after transplant than the general population, depending on the cancer type. Recent advances in cancer therapies have dramatically improved survival outcomes; however, patients with kidney transplants face unique challenges of immunosuppression management, cancer screening, and recurrence of cancer after transplant. Patients with a history of cancer tend to be excluded from transplant candidacy or are required to have long cancer-free wait time before wait-listing. The strategy of pretransplant wait time management may need to be revisited as cancer therapies improve, which is most applicable to patients with a history of multiple myeloma. In this review, we discuss several important topics in transplant onconephrology: the current recommendations for pretransplant wait times for transplant candidates with cancer histories, cancer screening post-transplant, post-transplant lymphoproliferative disorder, strategies for transplant patients with a history of multiple myeloma, and novel therapies for patients with post-transplant malignancies. With emerging novel cancer treatments, it is critical to have multidisciplinary discussions involving patients, caregivers, transplant nephrologists, and oncologists to achieve patient-oriented goals.

| S-EPMC9326185 | biostudies-literature

Incidence of post-transplant glomerulonephritis and its impact on graft outcome.

Project description:BACKGROUND:Herein, the significance of post-transplant glomerulonephritis (PTGN) has been revisited to investigate whether PTGN induces allograft failure. The aim of this study was to identify the incidence of PTGN and its association with allograft failure, as well as to analyze the risk factors for PTGN. METHODS:Among the 996 Korean patients who underwent kidney transplantation in a multicenter cohort from 1995 to 2010, 764 patients were enrolled in this study. RESULTS:The incidence rate of PTGN was 9.7% and 17.0% at 5 and 10 years of follow-up, respectively. PTGN was diagnosed in 17.8% of the recipients with results of biopsy tests or clinical diagnosis identifying glomerular diseases as the underlying cause, compared with 0.0%, 4.4%, 4.9%, 5.5%, and 5.7% of the recipients with renal vascular diseases, renal interstitial diseases/pyelonephritis/uropathy, diabetic renal disease, hereditary renal diseases, and diseases with unknown etiologies, respectively. Allograft survival was significantly decreased in patients with PTGN. PTGN was associated with a fourfold increase in graft failure with a hazard ratio of 7.11 for both acute rejection and PTGN. Results of the risk factor analysis for PTGN revealed that the underlying glomerular renal diseases and treatment methods using drugs such as tacrolimus and basiliximab significantly increased PTGN development, after adjusting for other risk factors. CONCLUSION:We conclude that PTGN is strongly associated with poor kidney allograft survival. Therefore, optimal management of recurrent or de novo GN should be the critical focus of post-transplant care.

| S-EPMC4716107 | biostudies-literature

Mesenchymal stem cells as feeder cells for pancreatic islet transplants.

Project description:Allogeneic islet transplantation serves as a source of insulin-secreting beta-cells for the maintenance of normal glucose levels and treatment of diabetes. However, limited availability of islets, high rates of islet graft failure, and the need for life-long non-specific immunosuppressive therapy are major obstacles to the widespread application of this therapeutic approach. To overcome these problems, pancreatic islet transplantation was recently suggested as a potential target of the "therapeutic plasticity" of adult stem cells. In fact, new results suggest that stem/precursor cells, and mesenchymal stem cells in particular, co-transplanted with islets can promote tissue engraftment and beta-cell survival via bystander mechanisms, mainly exerted by creating a milieu of cytoprotective and immunomodulatory molecules. This evidence consistently challenges the limited view that stem/precursor cells work exclusively through beta-cell replacement in diabetes therapy. It proposes that stem cells also act as "feeder" cells for islets, and supporter of graft protection, tissue revascularization, and immune acceptance. This article reviews the experience of using stem cell co-transplantation as strategy to improve islet transplantation. It highlights that comprehension of the mechanisms involved will help to identify new molecular targets and promote development of new pharmacological strategies to treat type 1 and type 2 diabetes patients.

| S-EPMC2989786 | biostudies-literature

Effects of Composition of Alginate-Polyethylene Glycol Microcapsules and Transplant Site on Encapsulated Islet Graft Outcomes in Mice.

Project description:BackgroundUnderstanding the effects of capsule composition and transplantation site on graft outcomes of encapsulated islets will aid in the development of more effective strategies for islet transplantation without immunosuppression.MethodsHere, we evaluated the effects of transplanting alginate (ALG)-based microcapsules (Micro) in the confined and well-vascularized epididymal fat pad (EFP) site, a model of the human omentum, as opposed to free-floating in the intraperitoneal cavity (IP) in mice. We also examined the effects of reinforcing ALG with polyethylene glycol (PEG). To allow transplantation in the EFP site, we minimized capsule size to 500 ± 17 ?m. Unlike ALG, PEG resists osmotic stress, hence we generated hybrid microcapsules by mixing PEG and ALG (MicroMix) or by coating ALG capsules with a 15 ± 2 ?m PEG layer (Double).ResultsWe found improved engraftment of fully allogeneic BALB/c islets in Micro capsules transplanted in the EFP (median reversal time [MRT], 1 day) versus the IP site (MRT, 5 days; P < 0.01) in diabetic C57BL/6 mice and of Micro encapsulated (MRT, 8 days) versus naked (MRT, 36 days; P < 0.01) baboon islets transplanted in the EFP site. Although in vitro viability and functionality of islets within MicroMix and Double capsules were comparable to Micro, addition of PEG to ALG in MicroMix capsules improved engraftment of allogeneic islets in the IP site, but resulted deleterious in the EFP site, probably due to lower biocompatibility.ConclusionsOur results suggest that capsule composition and transplant site affect graft outcomes through their effects on nutrient availability, capsule stability, and biocompatibility.

| S-EPMC5642344 | biostudies-literature

Graft Function and Intermediate-Term Outcomes of Kidney Transplants Improved in the Last Decade: Analysis of the United States Kidney Transplant Database.

Project description:BackgroundPrevious analyses of the United States transplant database regarding long-term outcomes in kidney transplantation have shown minimal improvement in the rate of long-term graft loss. This study sought to analyze intermediate-term outcomes and graft function at 6 months in kidney transplantation in adult living and deceased donor recipients in the last decade.MethodsSurvival analysis was performed based on the year of transplant between 6 months and 3 years' posttransplant. The Chronic Kidney Disease Epidemiology Collaboration estimated glomerular filtration rate (eGFR) was determined at 6 months.ResultsThe unadjusted graft survival between 6 months and 3 years improved significantly in the latter half of the decade in both deceased and living donor kidney recipients. Cox analysis showed a 33% reduction in the rate of graft loss and that the improvement in graft survival was due to similar improvements in both death-censored graft and death with graft function survival. A 10% improvement in median eGFR occurred despite worsening donor demographics over time in both donor types. This improvement in eGFR and graft survival occurred in association with a consolidation of chronic discharge immunosuppression from a variety of combinations to over 85% of recipients receiving tacrolimus and mycophenolate derivative immunosuppression.ConclusionsIn the latter half of last decade graft survival improved in adult kidney transplant recipients. The improvement in graft survival occurred in temporal association with an improvement in median eGFR at 6 months and consolidation of discharge immunosuppression in most patients to tacrolimus and mycophenolate derivatives.

| S-EPMC5464785 | biostudies-literature

Higher recipient body mass index is associated with post-transplant delayed kidney graft function.

Project description:To examine whether a higher body mass index (BMI) in kidney recipients is associated with delayed graft function (DGF), we analyzed data from 11,836 hemodialysis patients in the Scientific Registry of Transplant Recipients who underwent kidney transplantation. The patient cohort included women, blacks, and diabetics; the average age was 49 years; and the mean BMI was 26.8 kg/m(2). After adjusting for relevant covariates, multivariate logistic regression analyses found that one standard deviation increase in pretransplant BMI was associated with a higher risk of DGF (odds ratio (OR) 1.35). Compared with patients with a pretransplant BMI of 22-24.99 kg/m(2), overweight patients (BMI 25-29.99 kg/m(2)), mild obesity patients (BMI 30-34.99 kg/m(2)), and moderate-to-severe obesity patients (BMI 35 kg/m(2) and over) had a significantly higher risk of DGF, with ORs of 1.30, 1.42, and 2.18, respectively. Similar associations were found in all subgroups of patients. Hence, pretransplant overweight or obesity is associated with an incrementally higher risk of DGF.

| S-EPMC5489124 | biostudies-literature

HLA discrepancy between graft and host rather than that graft and first donor impact the second transplant outcome.

Project description:Second allogeneic hematopoietic stem cell transplantation is a curative treatment option for patients with hematologic malignancies. However, it is unclear whether HLA discrepancy between graft and first donor has an impact on the outcome of second transplantation. We retrospectively analyzed 646 patients receiving second transplantation after an initial HLA mismatched transplantation. With regard to graft-versus-host, the one-allele mismatch (1 mismatch) group (SHR, 1.88; 95%CI: 0.79-4.45; P=0.163) and more than one-allele mismatch group (≥ 2 mismatch) (SHR, 1.84; 95%CI, 0.75-4.51; P=0.182) had higher risks of grade III-IV acute graft-versus-host disease (GvHD) compared to the HLA-matched (0 mismatch) group. In contrast, no difference in risk of acute GvHD was found among the 0, 1, and ≥ 2 mismatch group with respect to graft-versus-first donor. With regard to graft-versus-host, the ≥ 2 mismatch group showed a significantly higher risk of treatment-related mortality (SHR, 1.90; 95%CI, 1.04-3.50; P=0.038) compared to the 0 mismatch group, while the risk of relapse was slightly lower in the ≥ 2 mismatch group (SHR, 068; 95%CI, 0.44-1.06; P=0.086). In contrast, with regard to graft-versus-first donor, there were no significant differences in treatment-related mortality or relapse among the three groups. These findings suggested that HLA discrepancy between graft and host induces transplant-related immunological responses in second transplantation leading to an increase in treatment-related mortality, in contrast, the biological effects of HLA discrepancy between graft and first donor on outcome may be negligible.

| S-EPMC6518881 | biostudies-literature

Correlation between beta cell mass and glycemic control in type 1 diabetic recipients of islet cell graft.

Project description:Islet grafts can induce insulin independence in type 1 diabetic patients, but their function is variable with only 10% insulin independence after 5 years. We investigated whether cultured grafts with defined beta cell number help standardize metabolic outcome. Nonuremic C-peptide-negative patients received an intraportal graft with 0.5-5.0 x 10(6) beta cells per kilogram of body weight (kg BW) under antithymocyte globulin and mycophenolate mofetil plus tacrolimus. Metabolic outcome at posttransplant (PT) month 2 was used to decide on a second graft under maintenance mycophenolate mofetil/tacrolimus. Graft function was defined by C-peptide >0.5 ng/ml and reduced insulin needs, metabolic control by reductions in HbA(1c), glycemia coefficient of variation, and hypoglycemia. At PT month 2, graft function was present in 16 of 17 recipients of >2 x 10(6) beta cells per kg BW versus 0 of 5 with lower number. The nine patients with C-peptide >1 ng/ml and glycemia coefficient of variation of <25% did not receive a second graft; five of them were insulin-independent until PT month 12. The 12 others received a second implant; it achieved insulin-independence at PT month 12 when the first and second graft contained >2 x 10(6) beta cells per kg BW. Of the 20 recipients of at least one graft with >2 x 10(6) beta cells per kg BW, 17 maintained graft function and metabolic control up to PT month 12. At PT month 12, beta cell function in insulin-independent patients ranged around 25% of age-matched control values. Thus, 1-year metabolic control can be reproducibly achieved and standardized by cultured islet cell grafts with defined beta cell number.

| S-EPMC1859948 | biostudies-literature

Primary graft function, metabolic control, and graft survival after islet transplantation.

Project description:OBJECTIVE To investigate the influence of primary graft function (PGF) on graft survival and metabolic control after islet transplantation with the Edmonton protocol. RESEARCH DESIGN AND METHODS A total of 14 consecutive patients with brittle type 1 diabetes were enrolled in this phase 2 study and received median 12,479 islet equivalents per kilogram of body weight (interquartile range 11,072-15,755) in two or three sequential infusions within 67 days (44-95). PGF was estimated 1 month after the last infusion by the beta-score, a previously validated index (range 0-8) based on insulin or oral treatment requirements, plasma C-peptide, blood glucose, and A1C. Primary outcome was graft survival, defined as insulin independence with A1C < or =6.5%. RESULTS All patients gained insulin independence within 12 days (6-23) after the last infusion. PGF was optimal (beta-score > or =7) in nine patients and suboptimal (beta-score < or =6) in five. At last follow-up, 3.3 years (2.8-4.0) after islet transplantation, eight patients (57%) remained insulin independent with A1C < or =6.5%, including seven patients with optimal PGF (78%) and one with suboptimal PGF (20%) (P = 0.01, log-rank test). Graft survival was not significantly influenced by HLA mismatches or by preexisting islet autoantibodies. A1C, mean glucose, glucose variability (assessed with continuous glucose monitoring system), and glucose tolerance (using an oral glucose tolerance test) were markedly improved when compared with baseline values and were significantly lower in patients with optimal PGF than in those with suboptimal PGF. CONCLUSIONS Optimal PGF was associated with prolonged graft survival and better metabolic control after islet transplantation. This early outcome may represent a valuable end point in future clinical trials.

| S-EPMC2713623 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data