Immunosuppression withdrawal in living-donor renal transplant recipients following induction with antithymocyte globulin and rituximab: Results of a prospective clinical trial.

Durable tolerance in kidney transplant recipients remains an important but elusive goal. We hypothesized that adding B cell depletion to T cell depletion would generate an immune milieu postreconstitution dominated by immature transitional B cells, favoring tolerance. The Immune Tolerance Network ITN039ST Research Study of ATG and Rituximab in Renal Transplantation was a prospective multicenter pilot study of live donor kidney transplant recipients who received induction with rabbit antithymocyte globulin and rituximab and initiated immunosuppression (IS) withdrawal (ISW) at 26 weeks. The primary endpoint was freedom from rejection at 52 weeks post-ISW. Six of the 10 subjects successfully completed ISW. Of these 6 subjects, 4 restarted immunosuppressive medications due to acute rejection or recurrent disease, 1 remains IS-free for over 9 years, and 1 was lost to follow-up after being IS-free for 42 weeks. There were no cases of patient or graft loss. CD19+ B cell frequencies returned to predepletion levels by 26 weeks posttransplant; immunoglobulin D+CD27--naïve B cells predominated. In contrast, memory cells dominated the repopulation of the T cell compartment. A regimen of combined B and T cell depletion did not generate the tolerogenic B cell profile observed in preclinical studies and did not lead to durable tolerance in the majority of kidney transplant recipients.

Early allogeneic immune modulation after establishment of donor hematopoietic cell-induced mixed chimerism in a nonhuman primate kidney transplant model.

Background: Mixed lymphohematopoietic chimerism is a proven strategy for achieving operational transplant tolerance, though the underlying immunologic mechanisms are incompletely understood. Methods: A post-transplant, non-myeloablative, tomotherapy-based total lymphoid (TLI) irradiation protocol combined with anti-thymocyte globulin and T cell co-stimulatory blockade (belatacept) induction was applied to a 3-5 MHC antigen mismatched rhesus macaque kidney and hematopoietic cell transplant model. Mechanistic investigations of early (60 days post-transplant) allogeneic immune modulation induced by mixed chimerism were conducted. Results: Chimeric animals demonstrated expansion of circulating and graft-infiltrating CD4+CD25+Foxp3+ regulatory T cells (Tregs), as well as increased differentiation of allo-protective CD8+ T cell phenotypes compared to naïve and non-chimeric animals. In vitro mixed lymphocyte reaction (MLR) responses and donor-specific antibody production were suppressed in animals with mixed chimerism. PD-1 upregulation was observed among CD8+ T effector memory (CD28-CD95+) subsets in chimeric hosts only. PD-1 blockade in donor-specific functional assays augmented MLR and cytotoxic responses and was associated with increased intracellular granzyme B and extracellular IFN-γ production. Conclusions: These studies demonstrated that donor immune cell engraftment was associated with early immunomodulation via mechanisms of homeostatic expansion of Tregs and early PD-1 upregulation among CD8+ T effector memory cells. These responses may contribute to TLI-based mixed chimerism-induced allogenic tolerance.

Twelve Thousand Kidney Transplants Over More Than 55 Y: A Single-center Experience.

Background: Kidney transplant outcomes have dramatically improved since the first successful transplant in 1954. In its early years, kidney transplantation was viewed more skeptically. Today it is considered the treatment of choice among patients with end-stage kidney disease. Methods: Our program performed its first kidney transplant in 1966 and recently performed our 12 000th kidney transplant. Here, we review and describe our experience with these 12 000 transplants. Transplant recipients were analyzed by decade of date of transplant: 1966-1975, 1976-1985, 1986-1995, 1996-2005, 2006-2015, and 2016-2022. Death-censored graft failure and mortality were outcomes of interest. Results: Of 12 000 kidneys, 247 were transplanted from 1966 to 1975, 1147 from 1976 to 1985, 2194 from 1986 to 1995, 3147 from 1996 to 2005, 3046 from 2006 to 2015, and 2219 from 2016 to 2022 compared with 1966-1975, there were statistically significant and progressively lower risks of death-censored graft failure at 1 y, 5 y, and at last follow-up in all subsequent eras. Although mortality at 1 y was lower in all subsequent eras after 1986-1995, there was no difference in mortality at 5 y or the last follow-up between eras. Conclusions: In this large cohort of 12 000 kidneys from a single center, we observed significant improvement in outcomes over time. Kidney transplantation remains a robust and ever-growing and improving field.

Risk factors and outcomes of persistent post-transplant hypotension among simultaneous pancreas and kidney transplant recipients.

BACKGROUND: The risk factors and outcomes associated with post- transplant hypotension after simultaneous pancreas and kidney (SPK) Transplantation are poorly defined. METHODS: SPK recipients at our center between 2010 and 2021 with functioning pancreas and kidney grafts for >6 months were included. Recipients were then divided into three groups based on active medications for the treatment of hypo-or hypertension at 6-months post-transplant: those with normal blood pressure (NBP) not requiring medication (NBP group), those on antihypertensive medications (HTN group), and those on medications for hypotension (fludrocortisone and/or midodrine) (Hypotensive group). RESULTS: A total of 306 recipients were included in the study: 54 (18%) in the NBP group, 215 (70%) in the HTN group, and 37 (12%) in the Hypotensive group. On multivariate analysis, the use of T-depleting induction (aHR = 9.64, p = .0001, 95% Cl = 3.12-29.75), pre-transplant use of hypotensive medications (aHR = 4.53, p = .0003, 95% Cl = 1.98-10.38), and longer duration of dialysis (aHR = 1.02, p = .01, 95% Cl = 1.00-1.04) were associated with an increased risk of post-transplant hypotension. Post-transplant hypotension was not associated with an increased risk of death-censored kidney or pancreatic allograft failure, or patient death. CONCLUSION: Hypotension was common even 6 months post-SPK transplantation. With appropriate management, hypotension was not associated with detrimental graft or patient outcomes.

Physician Preferences when Selecting Candidates for Lower-Quality Kidney Offers.

BACKGROUND: In the United States, more than 50% of kidneys in the lowest 15% quality range (those with Kidney Donor Profile Index >85) are discarded. Studies suggest that using more of these kidneys could benefit patients waiting for a transplant. This study assesses the trade-offs physicians make when selecting recipients for lower-quality kidneys. METHODS: A discrete choice experiment (DCE) was administered to surgeons and nephrologists in the United States who are involved in kidney acceptance decisions. The DCE presented kidneys that varied in terms of Kidney Donor Profile Index, expected cold ischemia time, donor age, pump parameters, serum creatinine levels, glomerulosclerosis, donor diabetes status, and whether donation was made after circulatory death. Candidate characteristics included recipients' age, diabetes history, time on dialysis, ejection fraction, HLA mismatch, calculated panel reactive antibody, and Karnofsky performance score. Regression analysis was used to estimate acceptability weights associated with kidney and recipient characteristics. RESULTS: A total of 108 physicians completed the DCE. The likelihood of acceptance was significantly lower with deterioration of kidney quality, expected cold ischemia time at transplantation, and missing biopsy and pump information. Acceptance was prioritized for patients who were higher on the waiting list, younger recipients, those who have spent less time on dialysis, and those without a history of diabetes. Performance status (Karnofsky score) and calculated panel reactive antibody also had a statistically significant but smaller association. Finally, ejection fraction had a marginally significant association, and HLA match had no significant association with the acceptance of marginal kidneys. A group of respondents were found to be primarily concerned about cold ischemia time. CONCLUSIONS: In this DCE, physicians considered the recipient characteristics that inform expected post-transplant survival score when they decided whether to accept a marginal kidney for a given recipient.

Analysis of Individual Components of Frailty in Simultaneous Pancreas and Kidney, and Solitary Pancreas Transplant Recipients.

Backgrounds: It is not known which of the 5 components of the Fried frailty score have the most predictive value for outcomes in simultaneous pancreas-kidney transplant (SPK) and solitary pancreas transplant (SPT) recipients. Methods: In this study, we sought to investigate the association between pretransplant overall frailty and individual frailty components, with posttransplant outcomes among SPK and SPT recipients. Outcomes of interest were length of stay, kidney delayed graft function (K-DGF), readmission within 30 d after discharge, cardiovascular events, acute rejection, pancreas death-censored graft failure (DCGF), kidney DCGF, and death. Results: Of the individual frailty components among SPK (n = 113), only slow walk time was associated with an increased risk of mortality (adjusted odds ratio [aOR]: 4.99; P = 0.03). Among SPT (n = 49), higher sum frailty scores (coefficient correlation 0.29; P = 0.04) and weight loss (coefficient correlation = 0.30; P = 0.03) were associated with prolonged length of stay. Similarly, weight loss among SPT was associated with an increased risk of DCGF (aOR: 4.34; P = 0.049). Low grip strength was strongly associated with an increased risk of early readmission (aOR: 13.08; P = 0.008). Conclusions: We found that not all components of frailty contribute equally to predicting outcomes. Objective measurements of slow walk time, unintentional weight loss, and low grip strength were found to be associated with less optimal outcomes in pancreas transplant recipients. Targeted interventions may improve posttransplant outcomes.

A Randomized Controlled Trial of Envarsus Versus Immediate Release Tacrolimus in Kidney Transplant Recipients With Delayed Graft Function.

BACKGROUND: The incidence of delayed graft function (DGF) among kidney transplant recipients (KTRs) in the United States continues to increase. The effect of immediate-release tacrolimus (tacrolimus) compared with extended-release tacrolimus (Envarsus) among recipients with DGF is unknown. METHODS: This was a single-center open-label randomized control trial among KTRs with DGF (ClinicalTrials. gov, NCT03864926). KTRs were randomized either to continue on tacrolimus or switch to Envarsus at a 1:1 ratio. Duration of DGF (study period), number of dialysis treatments, and need for adjustment of calcineurin inhibitor (CNI) doses during the study period were outcomes of interest. RESULTS: A total of 100 KTRs were enrolled, 50 in the Envarsus arm and 50 in the tacrolimus arm; of those, 49 in the Envarsus arm and 48 in the tacrolimus arm were included for analysis. There were no differences in the baseline characteristics, all P > .5, except donors in the Envarsus arm had higher body mass index (mean body mass index 32.9 ± 11.3 vs 29.4 ± 7.6 kg/m2 [P = .007]) compared with the tacrolimus arm. The median duration of DGF (5 days vs 4 days, P = .71) and the number of dialysis treatments (2 vs 2, P = .83) were similar between the groups. However, the median number of CNI dose adjustments during the study period in the Envarsus group was significantly lower (3 vs 4, P = .002). CONCLUSIONS: Envarsus patients had less fluctuation in the CNI level, requiring fewer CNI dose adjustments. However, there were no differences in the DGF recovery duration or number of dialysis treatments.

Helical TomoTherapy Total Lymphoid Irradiation and Hematopoietic Cell Transplantation for Kidney Transplant Tolerance in Rhesus Macaques.

Development of a post-transplant kidney transplant tolerance induction protocol involving a novel total lymphoid irradiation (TLI) conditioning method in a rhesus macaque model is described. We examined the feasibility of acheiving tolerance to MHC 1-haplotype matched kidney transplants by establishing a mixed chimeric state with infusion of donor hematopoietic cells (HC) using TomoTherapy TLI. The chimeric state was hypothesized to permit the elimination of all immunosuppressive (IS) medications while preserving allograft function long-term without development of graft-versus-host-disease (GVHD) or rejection. An experimental group of 11 renal transplant recipients received the tolerance induction protocol and outcomes were compared to a control group (n = 7) that received the same conditioning but without donor HC infusion. Development of mixed chimerism and operational tolerance was accomplished in two recipients in the experimental group. Both recipients were withdrawn from all IS and continued to maintain normal renal allograft function for 4 years without rejection or GVHD. None of the animals in the control group achieved tolerance when IS was eliminated. This novel experimental model demonstrated the feasibility for inducing of long-term operational tolerance when mixed chimerism is achieved using a TLI post-transplant conditioning protocol in 1-haplotype matched non-human primate recipients of combined kidney and HC transplantation.

Master protocol to assess the long-term safety in kidney transplant recipients who previously received Medeor's cellular immunotherapy products: the MDR-105-SAE.

BACKGROUND: Immunosuppression in transplantation continues to be associated with a multitude of adverse effects. Induction of immune tolerance may be a viable strategy to reduce dependence on immunosuppression. Various trials are currently underway to assess the efficacy of this strategy. However, long-term safety data for these immune tolerance regimes has yet to be established. METHODS/DESIGN: At the completion of primary follow-up of various Medeor kidney transplant studies, subjects receiving cellular immunotherapy products will be followed annually as per protocolized schedule for up to an additional 84 months (7 years) to evaluate long-term safety. Long-term safety will be assessed by summarizing incidence of serious adverse events, adverse events leading to study withdrawal and hospitalization rates. DISCUSSION: This extension study will be an important step in evaluating safety issues pertaining to immune tolerance regimens, long-term effects of which are largely unknown. These data are essential for furthering an unrealized goal of kidney transplantation- graft longevity without the adverse effects from long-term immunosuppression. The study design utilizes the methodology of a master protocol, wherein multiple therapies can be assessed simultaneously with accompanied gathering of long-term safety data.

Higher Fasting Pretransplant C-peptide Levels in Type 2 Diabetics Undergoing Simultaneous Pancreas-kidney Transplantation Are Associated With Posttransplant Pancreatic Graft Dysfunction.

BACKGROUND: Among selected patients with type 2 diabetes mellitus (T2DM), simultaneous pancreas and kidney (SPK) transplants can be an effective option. However, data are limited about outcomes in T2DM SPK recipients based on the pretransplant C-peptide levels. METHODS: In this study, we reviewed all T2DM SPK recipients and categorized them based on the pretransplant fasting C-peptide levels into 3 groups: low (≤2 ng/mL), medium (>2-8 ng/mL), and high (>8 ng/mL). Several measures of graft failures (GFs), graft dysfunction, and composite outcomes were of interest. RESULTS: There were a total of 76 SPK recipients (low, n = 14; medium, n = 47; high, n = 15). At the last follow-up, the low group did not reach any outcome; in contrast, 11 (23%) in the medium group and 5 (33%) in the high group reached the uncensored composite outcome; 6 (13%) in the medium group and 2 (13%) in the high group had GF; and 8 (17%) in the medium group and 4 (26.7%) in the high group reached the death-censored composite outcomes. In a fully adjusted model, each pretransplant C-peptide unit was not associated with an increased risk of the composite outcome, GF, or death-censored composite outcomes. However, in multivariate analysis with limited adjustment, pretransplant C-peptide was associated with the composite outcome (hazard ratio: 1.18, 95% confidence interval, 1.01-1.38; P = 0.03) and death-censored composite outcome (hazard ratio: 1.20; 95% confidence interval, 1.01-1.42; P = 0.03). CONCLUSIONS: Although limited by the small sample size, we found excellent outcomes among T2DM SPK recipients overall. However, higher levels of pretransplant C-peptide may be associated with inferior posttransplant outcomes that include graft dysfunction.

The John S. Najarian symposium: The past, present, and future of surgery and transplantation, May 20, 2022, Minneapolis, MN.

Dr John S Najarian (1927-2020), chairman of the Department of Surgery at the University of Minnesota from 1967 to 1993, was a pioneer in surgery, clinical immunology and transplantation. A Covid-delayed Festschrift was held in his honor on May 20, 2022. The speakers reflected on his myriad contributions to surgery, transplantation, and resident/fellow training, as well as current areas of ongoing research to improve clinical outcomes. Of note, Dr Najarian was a founder of the journal Clinical Transplantation.

Induction in Pancreas Transplantation: T-cell Depletion Versus IL-2 Receptor Blockade.

There is limited data exist on relative outcomes with T-depletion versus IL-2 receptor (IL2R) blockade induction in pancreas transplantation. Methods: We analyzed all patients who underwent simultaneous pancreas-kidney or pancreas transplant alone at our institution between January 1, 2011, and December 31, 2019. Results: Of 417 pancreas transplant recipients, 291 received induction with a T-depleting agent and 126 received induction with an IL2R blocker. No difference was detected in pancreas allograft death-censored (P = 0.7) or uncensored (P = 0.5) survival. Although pancreas rejection was more common overall (P = 0.03), this difference was no longer present in recipients at low immunologic risk (P = 0.08). Cytomegalovirus and bacterial infections were significantly more common in the patients who received T-cell depleting agents for induction (21% versus 11%, P = 0.03; 34% versus 23%, P = 0.04, respectively). On multivariate analysis, history of pancreas rejection (Hazard ratio (HR) = 4.7, P = 0.0001; 95% Confidence interval (CI), 2.16-10.12) and higher calculated panel reactive antibodies (HR = 1.01, P = 0.04; 95% CI, 1.0002-1.02) were associated with increased risk of pancreas allograft failure, but choice of induction was not (HR = 0.64, P = 0.3; 95% CI, 0.27-1.51). Further, on multivariate analysis, Cytomegalovirus infection was associated with increased risk of pancreas allograft rejection (HR = 1.78, P = 0.01; 95% CI, 1.11-2.87), but choice of induction was not (HR = 0.84, P = 0.46; 95% CI, 0.54-1.32). Similarly, bacterial infection was associated with increased risk of patient death (HR = 2.94, P = 0.04; 95% CI, 1.03-8.32). Conclusion: Our data suggest that IL-2 receptor blockade may be a reasonable choice of induction for pancreas transplant recipients at low immunologic risk.

Post-pancreatic transplant enteric leaks: The role of the salvage operation.

Enteric drainage in pancreas transplantation is complicated by an enteric leak in 5%-8%, frequently necessitating pancreatectomy. Pancreatic salvage outcomes are not well studied. Risk factors for enteric leak were examined and outcomes of attempted graft salvage were compared to immediate pancreatectomy. Pancreas transplants performed between 1995 and 2018 were reviewed. Donor, recipient, and organ variables including demographics, donor type, ischemic time, kidney donor profile index, and pancreas donor risk index were analyzed. Among 1153 patients, 33 experienced enteric leaks (2.9%). Donors of allografts that developed leak were older (37.9y vs. 29.0y, p = .001), had higher KDPI (37% vs. 24%, p < .001), higher pancreas donor risk index (1.83 vs. 1.32, p < .001), and longer cold ischemic time (16.5 vs. 14.8 h, p = .03). Intra-abdominal abscess and higher blood loss decreased the chance of successful salvage. Enteric leak increased 6-month graft loss risk (HR 13.9[CI 8.5-22.9], p < .001). However, 50% (n = 12) of allografts undergoing attempted salvage survived long-term. After 6 months of pancreas graft survival, salvage and non-leak groups had similar 5-year graft survival (82.5% vs. 81.5%) and mortality (90.9% vs. 93.5%). Enteric leaks remain a challenging complication. Pancreatic allograft salvage can be attempted in suitable patients and accomplished in 50% of cases without significantly increased graft failure or mortality risk.

The Presence of Donor-specific Antibodies Around the Time of Pancreas Graft Biopsy With Rejection Is Associated With an Increased Risk of Graft Failure.

BACKGROUND: Donor-specific antibodies (DSA) against HLA are an important biomarker predicting graft injury, rejection (Rej), and failure in various solid-organ transplant recipients. However, the impact of DSA with or without histopathological evidence of rejection among pancreas transplant recipients (PTRs) is unknown. METHODS: In this study, we included all PTRs at our center between 2005 and 2020, with pancreas allograft biopsy before March 31, 2021, and with DSA checked within 15 d of the biopsy. PTRs were divided into 4 groups based on the biopsy findings on the index biopsy and DSA status as Rej-/DSA-, Rej+/DSA-, Rej-/DSA+, and Rej+/DSA+. RESULTS: Two hundred two PTRs had a pancreas allograft biopsy during the study period. Thirty-nine were in Rej-/DSA-, 84 Rej+/DSA-, 24 Rej-/DSA+, and 55 Rej+/DSA+. The mean interval from transplant to index biopsy was not statistically different between the 4 groups. The most common type of rejection was T cell-mediated rejection; however, antibody-mediated rejection was more prevalent in the Rej+/DSA+ group. At 5 y postbiopsy, the rate of death-censored graft failure (DCGF) for Rej-/DSA- was 18%, 24% in Rej+/DSA-; 17% in Rej-/DSA+ and 36% in Rej+/DSA+ (P = 0.14). In univariate analysis, mixed rejection (hazard ratio [HR], 3.0; 95% confidence intervals [CI], 1.22-7.39; P = 0.02) along with solitary pancreas transplantation and Rej+/DSA+ were associated with DCGF. In multivariate analysis, compared with Rej-/DSA-, Rej+/DSA+ was significantly associated with DCGF (HR, 2.32; 95% CI, 1.03-5.20; P = 0.04); however, Rej+/DSA- was not (HR, 1.06; 95% CI, 0.32-3.56; P = 0.92). CONCLUSIONS: PTRs with pancreas allograft rejection and concomitant DSA have an increased risk of DCGF.

The Role of Procurement Biopsies in Kidney Acceptance Decision Making and Kidney Discard: Perceptions of Physicians, Nurse Coordinators, and OPO Staff and Directors.

Procurement biopsies suffer from challenges with quality and reproducibility and are linked to kidney discard. Nonetheless, procurement biopsies are obtained for the majority of kidneys in the United States, and biopsy findings are commonly relied upon in kidney acceptance decisions. Methods: We conducted in-depth, semistructured interviews with 30 surgeons, nephrologists, nurse coordinators, and organ procurement organization (OPO) staff and directors to assess perceptions of factors contributing to kidney discard and strategies to reduce kidney discard, with a focus on the role of procurement biopsies. Thematic analysis was used to analyze qualitative data. Results: Three main themes emerged: (1) participants emphasized the importance of biopsy findings in making acceptance decisions but expressed concerns about a lack of standardization and quality control; (2) participants reported large variations in the level of importance placed on biopsy findings, the level of reliance on glomerulosclerosis in particular, and the cutoffs used; and (3) participants disagreed about how often procurement biopsies should be taken, with some supporting stricter limits on which kidneys are biopsied and others preferring a biopsy for most kidney offers. Conclusions: These findings support the development of standard practices for which kidneys require biopsy, how the biopsy material is prepared, and how the biopsy is interpreted. Variability in kidney acceptance practices across centers and the use of biopsy findings in guiding recipient selection also lend support to policies to allocate kidneys with suboptimal histological findings to the centers that are willing to use such kidneys and the patients who could most benefit from such offers.

Robust engraftment of fetal nonhuman primate CD34-positive cells in immune-deficient mice.

Nonhuman primates (NHPs) represent one of the most important models for preclinical studies of novel biomedical interventions. In contrast with small animal models, however, widespread utilization of NHPs is restricted by cost, logistics, and availability. Therefore, we sought to develop a translational primatized mouse model, akin to a humanized mouse, to allow for high-throughput in vivo experimentation leveraged to inform large animal immunology-based studies. We found that adult rhesus macaque mobilized blood (AMb) CD34+-enriched hematopoietic stem and progenitor cells (HSPCs) engrafted at low but persistent levels in immune-deficient mice harboring transgenes for human (NHP cross-reactive) GM-CSF and IL3, but did not in mice with wild-type murine cytokines lacking NHP cross-reactivity. To enhance engraftment, fetal liver-derived HSPCs were selected as the infusion product based on an increased CD34hi fraction compared with AMb and bone marrow. Coupled with cotransplantation of rhesus fetal thymic fragments beneath the mouse kidney capsule, fetal liver-derived HSPC infusion in cytokine-transgenic mice yielded robust multilineage lymphohematopoietic engraftment. The emergent immune system recapitulated that of the fetal monkey, with similar relative frequencies of lymphocyte, granulocyte, and monocyte subsets within the thymic, secondary lymphoid, and peripheral compartments. Importantly, while exhibiting a predominantly naïve phenotype, in vitro functional assays demonstrated robust cellular activation in response to nonspecific and allogenic stimuli. This primatized mouse represents a viable and translatable model for the study of hematopoietic stem cell physiology, immune development, and functional immunology in NHPs. Summary Sentence: Engraftment of rhesus macaque hematopoietic tissues in immune-deficient mice yields a robust BLT/NeoThy-type primatized mouse model for studying nonhuman primate hematopoiesis and immune function in vivo.

Early Increases in Posttransplant Pancreatic Enzymes Are Associated With Surgical Complications But Not Graft Failure Among Pancreas Transplant Recipients.

OBJECTIVES: This study aimed to find the association between immediate postoperative increases in pancreatic enzymes and posttransplant complications among pancreas transplant recipients (PTRs). METHODS: We analyzed all PTRs transplanted at the University of Wisconsin between June 2009 and September 2018. Enzyme levels were presented as a ratio of absolute numbers to the upper limit of normal value, with value >1 considered as abnormal. We specifically evaluated bleeding, fluid collections, and thrombosis complications based on the amylase or lipase ratios on day 1 (Amylase1, Lipase1) and maximum ratios within 5 days of transplant (Amylasemax, Lipasemax). For early complications, we focused on technical complications that occurred within 90 days of transplant. For long-term outcomes, we assessed patient and graft survival, and rejections. RESULTS: There were a total of 443 PTRs, 287 were simultaneous pancreas and kidney recipients, and 156 were solitary pancreas recipients. Higher Amylase1, Liplase1, Amylasemax, and Lipasemax were associated with an increase in early complications, mainly need for pancreatectomy, fluid collections, bleeding complications, or graft thrombosis, particularly in the solitary pancreas group. CONCLUSIONS: Our finding suggests that cases of early perioperative enzyme increase merit consideration for early imaging investigation to mitigate detrimental outcomes.

Patient and Clinician Perceptions of Informed Consent and Decision Making About Accepting KDPI > 85 Kidneys.

BACKGROUND: Although the impact of the kidney donor profile index (KDPI) on kidney discard is well researched, less is known about how patients make decisions about whether to give consent for KDPI > 85 kidney offers. METHODS: We conducted in-depth, semistructured interviews with 16 transplant recipients, 15 transplant candidates, and 23 clinicians (transplant surgeons, nephrologists, and nurse coordinators) to assess and compare perceptions of transplant education, informed consent for KDPI > 85 kidneys' and the decision-making process for accepting kidney offers. Thematic analysis was used to analyze qualitative data. RESULTS: Four themes emerged: (1) patients reported uncertainty about the meaning of KDPI or could not recall information about KDPI; (2) patients reported uncertainty about their KDPI > 85 consent status and a limited role in KDPI > 85 consent decision making; (3) patients' reported willingness to consider KDPI > 85 kidneys depended on their age, health status, and experiences with dialysis, and thus it changed over time; (4) patients' underestimated the survival benefit of transplantation compared with dialysis, which could affect their KDPI > 85 consent decision making. CONCLUSIONS: To better support patients' informed decision making about accepting KDPI > 85 kidneys, centers must ensure that all patients receive education about the trade-offs between accepting a KDPI > 85 kidney and remaining on dialysis. Additionally, education about KDPI and discussions about informed consent for KDPI > 85 kidneys must be repeated at multiple time points while patients are on the waiting list.

Association of human leukocyte antigen mismatches between donor-recipient and donor-donor in pancreas after kidney transplant recipients.

The effects of HLA mismatching on pancreas outcomes among pancreas after kidney (PAK) recipients are undefined. Outcomes might potentially differ depending on whether there is a mismatch between pancreas donor and recipient (PD-R) or pancreas donor and kidney donor(PD-KD). All primary PAK at our centre were included in this study. Patients were divided into two groups based on the degree of HLA mismatching: low (L-MM) as 0-4 and high (H-MM) as 5-6. We analysed all (N = 73) PAK for PD-R mismatch and the subset of PAK for PD-KD mismatch (N = 71). Comparing PD-R L-MM (n = 39) and H-MM (n = 34) PAKs, we observed no difference in the rate of pancreas graft failure. There was also no difference in the rate of rejection (L-MM 33% vs. H-MM 41%) or the severity of rejection. However, we observed a significantly (P < 0.01) shorter time to acute pancreas rejection in the H-MM group (6.8 ± 8.7 mo) versus the L-MM cohort (29.0 ± 36.2 mo) (P < 0.001). Similar to the PD-R mismatched cohort, we did not observe a detrimental effect of HLA mismatching on graft outcomes in the PD-KD cohort; time to rejection was again shorter in the H-MM subset. In this study, we found no impact of HLA mismatch on either pancreas graft survival or rejection rates, though rejection occurred earlier in high mismatched PAK transplants.