Age and Pre-operative HbA1c levels affect renal function compensation in living kidney donors.

OBJECTIVES: About 90% of Japanese kidney transplantations are conducted from living donors, and their safety and the maintenance of their renal function are critical. This study aims to identify factors that affect the compensation of renal function in living kidney donors after donor nephrectomy. METHOD: In a retrospective cohort study, we reviewed data from 120 patients who underwent nephrectomy as living kidney transplant donors in our department from 2012 to 2021. Univariable and multivariable linear regression analyses were performed for donor factors affecting renal function after donor nephrectomy. RESULT: The multivariable linear regression model revealed that the donor's age (p = 0.025), preoperative estimated Glomerular Filtration Rate (eGFR) (p < 0.001), and hemoglobin A1c (HbA1c) (p = 0.043) were independent risk factors for eGFR at six months after nephrectomy. The eGFR deterioration was more strongly associated with age in females than in males, whereas higher HbA1c values were more strongly associated with eGFR deterioration in males. Higher donor age and higher HbA1c each enhance the deterioration of eGFR six months after living donor nephrectomy. The data suggest that old age in especially female donors and preoperative higher HbA1c in male donors have a harmful impact on their renal function compensation.

Adherence to recommended vaccination policies for pre- and post-solid organ transplantation patients: A national questionnaire survey in Japan.

BACKGROUND: Pre-transplant vaccination is recommended for patients undergoing solid organ transplantation (SOT). While appropriate vaccination protocols are implemented at some facilities, transplantation is sometimes performed with inadequate preoperative vaccine management. Vaccination rates vary across facilities, but those of SOT centers in Japan have never been investigated. This study aimed to conduct a nationwide questionnaire survey to assess pre- and post-transplant vaccination policies among SOT facilities in Japan. METHODS: The survey was conducted from September to November 2022. All registered (n = 221) solid organ (namely, the lungs, liver, kidneys, pancreas, heart, and small intestine) transplant facilities were asked to complete a web-based survey. RESULTS: The survey response rate was 70.2 %. Live and inactivated vaccines were recommended at 64.9 % and 68.9 % of the responding facilities, respectively. The following vaccines were incorporated into the vaccination protocols of facilities: pneumococcal vaccine, 31.7 % (13-valent pneumococcal conjugate vaccine) and 65.4 % (23-valent pneumococcal polysaccharide vaccine); hepatitis B virus vaccine, 67.3 %; severe acute respiratory syndrome coronavirus 2 vaccine, 73.1 %; influenza vaccine, 73.1 %; and zoster vaccines, 23.1 %. The reasons for unresponsiveness to vaccinations included inadequate time before transplantation (60.3 %), cost burden (41.1 %), high number of vaccinations (21.9 %), no recognition of the need for vaccination (17.9 %), and the requirement to explain the need for vaccination (15.2 %). CONCLUSIONS: Our study revealed gaps in vaccination practices across nationwide facilities in Japan. The findings indicate the importance of promoting scheduled efficiency and encouraging the national health system to reduce vaccine costs with the support of public subsidies.

Size-mismatched transplantation from large donors to small recipients is associated with pancreas graft thrombosis: A retrospective national observational study.

INTRODUCTION: Donor-recipient (D/R) size mismatch has been evaluated for a number of organs but not for pancreas transplantation. METHODS: We retrospectively evaluated 438 patients who had undergone pancreas transplantation. The D/R body surface area (BSA) ratio was calculated, and the relationship between the ratio and graft prognosis was evaluated. We divided the patients into two groups and evaluated graft survival. The incidence of pancreas graft thrombosis resulting in graft failure within 14 days and 1-year graft survival were compared using Kaplan-Meier curves, and the prognostic factors associated with graft thrombosis were identified by univariate and multivariate analyses. RESULTS: The mean/median donor and recipient BSAs were 1.63 m2 /1.65 m2 , and 1.57 m2 /1.55 m2 , respectively; the mean and median D/R BSAs were both 1.05. The receiver operating characteristic curve cutoff for the D/R BSA ratio was 1.09, and significant differences were identified between patients with ratios of ≥1.09 (high group) versus <1.09 (low group). The incidence of graft thrombosis resulting in pancreas graft failure within 14 days was significantly higher in the high group than in the low group (p < .01). One-year overall and death-censored pancreas graft survival were significantly higher in the low group than in the high group (p < .01). Multivariate analysis identified recipient height, donor BSA, and donor hemoglobin A1c as significant independent factors for graft thrombosis. Cubic spline curve analysis indicated an increased risk of graft thrombosis with increasing D/R BSA ratio. CONCLUSION: D/R size mismatch is associated with graft thrombosis after pancreas transplantation.

Pancreas transplantation improves the quality of life of Japanese type 1 diabetes patients with diabetic kidney disease.

Objectives: Type 1 diabetes mellitus (T1DM) patients with diabetic kidney disease-induced kidney failure have a significantly impaired quality of life (QOL), resulting in a high level of physical, mental, and social anxiety. In this study, we evaluated the QOL of T1DM patients on the list for pancreas transplantation (PTx) at their registration, and determined whether PTx improved their QOL. Methods: There were 58 patients (men/women, 22/36; mean age, 42.8±8.0 years) with T1DM and who were registered on the waiting list for PTx. Quantitative QOL assessment was performed using the Medical Health Survey Short Form (SF-36) version 2. Changes in the QOL before and after PTx were also examined in 24 of these patients. Results: The mean value of each endpoint and the summary score of the SF-36 physical (PCS), mental (MCS), and role (RCS) components were all below the national normal level at PTx registration. No significant difference in QOL scores was observed in the intergroup comparison of 35 patients on dialysis, 13 patients without dialysis, and ten patients after kidney transplantation. The 24 patients who underwent PTx showed improvement in PCS, MCS, and most SF-36 scores. Conclusion: T1DM patients waiting for PTx had a decreased QOL, regardless of dialysis, and PTx improved their QOL.

An Examination of Packing Methods for Grafts to Prevent Freezing Injury during Transportation for Liver Transplantation.

BACKGROUND: University of Wisconsin solution (UW) may freeze at temperatures below -0.7 °C, damaging the graft. The present study assessed the effectiveness of the liver graft package protocol, which recommends filling a package with sufficient liquid to prevent grafts from sustaining freezing injury. METHODS: We filled ice cubes at two temperatures (-80 and -20 °C) around packages and performed a comparative study with four groups based on the temperature and filling of the second layer with lactated Ringer's solution (LR) (A: -80 °C, LR-; B: -80 °C, LR+; C: -20 °C, LR-; D: -20 °C, LR+). The bovine liver was used as a graft and preserved for 6 h in the first isolation bag filled with UW. RESULTS: While temperatures dropped below -0.7 °C at some points for 6 h in groups A, B, C, they never dropped to -0.7 °C in group D. The macroscopic findings in groups A, B, C showed freezing of the UW and grafts, but no such results in group D. A pathological study including electron microscopy showed freezing injury in groups A, B, and C but no significant changes in group D. CONCLUSIONS: The graft package protocol prevents freezing of the UW and liver grafts.

Impact of B Cell Depletion on COVID-19 in Kidney Transplant Recipients.

Kidney transplant recipients are patients at high risk for coronavirus disease 2019 (COVID-19) due to being on immunosuppressive therapy. B cell depletion therapy, including rituximab, is an important strategy for ABO-incompatible transplants. However, knowledge about the effect of B cell depletion therapy on COVID-19 is lacking. Thirty kidney transplant recipients who developed COVID-19 were included in this study. To examine the impact of B cell depletion therapy, we retrospectively investigated the relationship between the background of the patients and the clinical outcome. Of the 30 patients, 13 received B cell depletion therapy. The median time between transplant and onset of COVID-19 was 6.1 years after transplantation; however, nine cases remained markedly depleted of CD19(+) cells (<4.0%). The patients were assigned to the normal (n = 21) and depletion groups (n = 9). Progression rates in the depletion and normal groups were 55.6% and 9.5%, respectively (p = 0.014). Furthermore, the survival rate was significantly lower in the depletion group (100% in the normal group vs. 66.7% in the depletion group; p = 0.021). B cell depletion therapy may have long-term effects and increase the risk of COVID-19 in kidney transplant recipients.

Utilization of the Pancreas From Donors With an Extremely High Pancreas Donor Risk Index: Report of the National Registry of Pancreas Transplantation.

Pancreas transplants from expanded criteria donors are performed widely in Japan because there is a shortage of brain-dead donors. However, the effectiveness of this strategy is unknown. We retrospectively studied 371 pancreas transplants to evaluate the possibility of pancreas transplantation from expanded criteria donors by the Pancreas Donor Risk Index (PDRI). Patients were divided into five groups according to quintiles of PDRI values (Q1-Q5). The 1-year pancreas graft survival rates were 94.5% for Q1, 91.9% for Q2, 90.5% for Q3, 89.3% for Q4, and 79.6% for Q5, and were significantly lower with a lower PDRI (p = 0.04). A multivariate analysis showed that the PDRI, donor hemoglobin A1c values, and pancreas transplantation alone significantly predicted 1-year pancreas graft survival (all p < 0.05). Spline curve analysis showed that the PDRI was incrementally associated with an increased risk of 1-year graft failure. In the group with a PDRI ≥ 2.87, 8/56 patients had graft failures within 1 month, and all were due to graft thrombosis. The PDRI is a prognostic factor related to the 1-year graft survival rate. However, pancreas transplantation from high-PDRI donors shows acceptable results and could be an alternative when the donor pool is insufficient.

Total Cell-Free DNA as a Noninvasive Biomarker of a Delayed Graft Function After Kidney Transplantation From Donors After Cardiac Death.

BACKGROUND: Because of the organ shortage, donation after cardiac death (DCD) kidney transplantation (KTx) is an alternative way of achieving KTx using brain-dead donors (BDs). Although the prognosis of DCD-KTx is improving, the graft suffers from delayed graft function (DGF), the management of which is essential. With progress in understanding the characteristics of cell-free DNA (CF-DNA), we consider plasma total CF-DNA (tCF-DNA) to be a useful biomarker for predicting DGF in DCD-KTx. STUDY DESIGN AND METHOD: Consecutive patients from living donors (LDs; n = 9), BDs (n = 8), or DCD donors (n = 13) were enrolled. Plasma samples were collected after KTx and on postoperative days 3 and 5. CF-DNA was isolated, and tCF-DNA was quantified using the TapeStation 2200 software program. RESULTS: The tCF-DNA levels after BD-KTx and DCD-KTx were higher than those after LD-KTx (LD, 78 ± 27 (ng/mL); BD, 99 ± 20; DCD, 150 ± 23); the difference between DCD-KTx and LD-KTx was statistically significant (P < .05). The tCF-DNA levels declined at postoperative day 5 (LD, 45 ± 10; BD, 51 ± 11; DCD, 66 ± 13). tCF-DNA levels were significantly increased in patients with DGF after KTx (DGF, 139 ± 22; immediate function, 91 ± 18; P < .05). The tCF-DNA level was correlated with the duration of DGF (r = 0.5825, P < .05). CONCLUSION: Although the mechanism underlying DNA release from transplanted grafts into the recipient circulation remains unclear, cell death by apoptosis or necrosis and the active secretion of the immune system may play important roles in DGF. These data suggest that monitoring tCF-DNA may help predict graft recovery after DCD-KTx.

Outcomes of Pancreas Transplantation for Lower-Ranked Candidates.

BACKGROUND: To perform more pancreas transplantation (PTx), our center sometimes performs pancreas transplantation for candidates ranked sixth place or lower. In this study, we analyzed the outcomes of PTx performed in our center to compare the outcomes of higher- and lower-ranked candidates. METHODS: Seventy-two cases in which PTx was performed at our center were divided into 2 groups according to the candidate's rank. Cases in which PTx was performed for candidates up to fifth place were classified into the higher rank candidate group (HRC group; n = 48), whereas PTx for candidates who were ranked sixth place or lower were classified into the lower rank candidate group (LRC group; n = 24). The outcomes of PTx were retrospectively compared. RESULTS: Although the LRC group included a greater number of older donors (age ≥60 years), a greater number of donors with deteriorated renal function, and a greater number of HLA mismatches, the 1- and 5-year patient survival rates in the HRC group were 91.6% and 91.6%, respectively, compared with 95.8% and 87.0%, respectively, in the LRC group (P = .755). In terms of both pancreas and kidney graft survival, there were no significant differences between the 2 groups. Additionally, there were no significant differences between the 2 groups regarding the glucagon stimulation test and 75 g OGTT results, insulin independence rate, HbA1c, or serum creatinine level after transplantation. CONCLUSIONS: In Japan, where there is a severe donor shortage, the performance of transplantation for lower-ranked candidates would increase the number of opportunities for patients to receive PTx.

First Multicenter Clinical Trial on Machine Perfusion Preservation for Marginal Donor Kidney Transplantation in Japan.

BACKGROUND: Machine perfusion has not been widely used because of its low demand in Japan; however, we believe its advantages may increase the number of organ transplants. METHODS: Here, we report the first clinical trial of machine perfusion for kidney transplantation in Japan. We used the CMP-X08 perfusion device (Chuo-Seiko Co, Ltd, Asahikawa, Hokkaido, Japan) to preserve the donated organs. The flow rate, perfusion pressure, renal resistance, and temperature were monitored during continuous hypothermic perfusion. RESULTS: From August 2020 to the present, 13 cases of perfusion-preserved kidney transplantation have been performed. Of these, ten and 3 cases were performed using organs donated after brain death (DBD) and cardiac death (DCD), respectively. The average age of the recipients was 55.9 ± 7.3 (45-66) years. The average dialysis period was 14.8 ± 8.4 (0-26) years. The donor's final creatinine level before organ retrieval was 1.58 ± 1.0 (0.46-3.07) mg/dL. The warm ischemic times of the 3 DCD donors were 3, 12, and 18 minutes. The average total ischemic time was 12.0 ± 3.7 (7.17-19.88) hours. The average MP time was 140 (60-240) minutes. A total of 7 cases had delayed graft function. The best creatinine level during hospitalization was 1.17 ± 0.43 (0.71-1.85) mg/dL. There were no primary non-functional cases, and perfusion preservation was safely performed in all cases. CONCLUSIONS: Therefore, we present this report as the first clinical trial on machine perfusion for kidney transplantation from marginal donors with DBD and DCD in Japan.

Different timing and risk factors of cause-specific pancreas graft loss after simultaneous pancreas kidney transplantation.

In cases after pancreas transplantation (PTx), the pancreas graft might be lost for various reasons, including a pancreatoduodenal graft-related complication or patient death with a functioning graft. Although the causes seem to have distinct characteristics, the causes of pancreas graft loss have not been characterized. This study aimed to characterize the causes of pancreas graft loss by analyzing data from a Japanese nationwide registry. This study included 391 patients who received simultaneous pancreas-kidney transplantation among 461 patients with PTx during the study period in approved institutions in Japan. We characterized each cause in terms of the timing of the cause-specific graft loss and preoperative factors associated with graft loss based on nationwide data from a Japanese nationwide registry. Among the 391 cases, 113 lost the pancreas graft due to patient death with a functioning graft (DWFG; n = 34, 44.2%), graft thrombus (n = 22, 28.6%), or chronic rejection (CR; n = 7, 9.1%). Average (± standard deviation) time from PTx to graft loss due to DWFG, graft thrombus, and CR was 3.70 ± 4.36, 0.02 ± 0.01, and 2.37 ± 2.08 years, respectively. Duration of type 1 diabetes mellitus and donor body mass index were significantly associated with pancreas graft loss due to DWFG and graft thrombus, respectively. This characterization showed that the timing and preoperative factors associated with pancreas graft loss were significantly different for different causes of graft loss. These results may inform PTx follow-up protocols to ensure that appropriate care is based on the cause of graft loss.

An Examination of Donor Factors That Impact the Results of the Glucagon Stimulation Test as an Assessment of the Pancreatic Graft Endocrine Function.

OBJECTIVES: Delta C-peptide derived by the glucagon stimulation test is a reliable value for the evaluation of the pancreatic endocrine function after pancreas transplantation. We examined the associations between delta C-peptide as pancreatic graft endocrine function and donor background factors. METHODS: Sixty-five cases of pancreatic transplantation from brain-dead donors, which were performed in our facility, were enrolled in this study. Enrolled recipients underwent a glucagon stimulation test within 1 to 3 months after transplantation to evaluate the pancreatic graft endocrine function with delta C-peptide to compare donor background factors. RESULTS: The following factors were associated with significant deterioration of the delta C-peptide: age of 50 years or greater, death from cerebrovascular accident, hemoglobin A1c level of 5.6% or greater, creatinine level of 1.0 mg/dL or greater, C-reactive protein level of 25 mg/dL or greater, and sodium level of 150 mmol/L or greater. In addition, increased numbers of these donor factors indicated significantly greater deterioration of the posttransplant pancreatic endocrine function ( P < 0.001). CONCLUSIONS: To secure insulin independence after pancreas transplantation, which means maintaining a delta C-peptide level of 1.0 ng/mL or greater on a glucagon stimulation test, the utilization of donors, who possesses more than equal to 3 of the donor factors identified in this study, should be carefully considered.

Impact of COVID-19 on living donor liver and kidney transplantation programs in Japan in 2020.

BACKGROUND: Although many transplant programs have been forced to suspend living donor transplants due to the emergence of coronavirus disease (COVID-19), there are relatively few real-time databases to assess center-level transplant activities. We aimed to delineate the actual impact of COVID-19 on living donor transplant programs and the resumption process in Japan. METHODS: In a nationwide survey, questionnaires were sent to 32 liver transplant programs that had performed at least more than one case of living donor liver transplantation in 2019 and 132 kidney transplant programs that had performed more than one living donor kidney transplantation in 2018. RESULTS: Thirty-one (96.9%) and 125 (94.7%) liver and kidney transplant programs responded, respectively. In the early pandemic period, 67.7% (21/31) of liver programs and 29.8% (37/125) of kidney programs were able to maintain transplant activities similar to those during the pre-pandemic period. After temporal suspension, 58.1% of kidney programs resumed their transplant activity after the number of local COVID-19 cases peaked. Establishing institutional COVID-19 screening, triage, and therapeutic management protocols was mandatory to resume transplant activity for 64.5% and 67.7% of liver and kidney programs, respectively. In the future wave of COVID-19, 67.7% of liver programs would be affected by institutional COVID-19 intensive care unit-bound patient numbers, and 55.7% of kidney programs would stop if hospital-acquired severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection spreads. CONCLUSIONS: THIS NATIONWIDE SURVEY REVEALED FOR THE FIRST TIME HOW LIVING DONOR LIVER AND KIDNEY: transplant programs changed in response to the COVID-19 pandemic in a country where living donor transplantations are predominant.

Evaluation of the Efficacy and Effects of Common Hepatic Artery Reconstruction in Pancreas Transplantation: A Randomized Controlled Trial.

Maintenance of postoperative graft flow is important in pancreas transplantation. In Japan, reconstruction of the common hepatic artery is performed primarily to increase perfusion in the pancreatic head. We investigated the effects of common hepatic artery reconstruction on patient and graft survival and endocrine functions. Twenty-nine cases of pancreas transplantation were registered in the clinical trial. Of the 29 cases, four were excluded because of the risk of ischemia without reconstruction or complicated reconstruction due to a narrow artery. A total of 25 cases were randomized into two groups: 13 in the non-reconstructed group and 12 in the reconstructed group. The 1-year patient survival and graft survival rates of the non-reconstructed and reconstructed groups were 92.3% and 83.3%, and 91.7% and 82.5%, respectively. The incidence of complications in the two groups was comparable, with 38.5% (5/13 cases) in the non-reconstructed group and 33.3% (4/12 cases) in the reconstructed group. The results of the glucagon stimulation test and oral glucose tolerance test at 1 month and 1 year post-transplantation were comparable. Common hepatic artery reconstruction is not essential unless there is risk of ischemia. This study was registered at the University Hospital Medical Information Network Clinical Trials Registry under UMIN000027213.

The History of Clinical Islet Transplantation in Japan.

Islet transplantation shows the promise of being capable of relieving glucose instability and improving QOL of patients with type 1 diabetes that cannot be controlled due to severe hypoglycemia unawareness. In Japan, following the first human islet isolation from a donor after cardiac death in 2003 and the first clinical islet transplantation in 2004, islet transplantation was performed for the improvement of type 1 diabetes as a single-center trial in several centers. Although it was discontinued due to the possibility of contamination of collagenase by bovine brain component in 2007, the phase II clinical trial of islet transplantation started using ATG induction and a TNF-α inhibition protocol in 2012. The primary endpoints of this trial were the proportion of patients with HbA1c < 7.4% and freedom from severe hypoglycemic events at one year after the first islet cell infusion. In an interim analysis, this endpoint was achieved in 75% of cases. In April 2020, clinical islet transplantation was finally covered by health insurance in Japan, thanks to these outcomes. We herein introduce more than 20 years of history of clinical islet transplantation in Japan.

National survey on deceased donor organ transplantation during the COVID-19 pandemic in Japan.

PURPOSE: We investigated the status of deceased organ donation and transplantation through a questionnaire distributed to transplant centers in Japan during the COVID-19 pandemic. METHODS: The questionnaire was distributed electronically to 206 transplant centers for heart (n = 11), lung (n = 10), liver (n = 25), kidney (n = 130), pancreas (n = 18), and small intestine (n = 12) transplantation. Organ donations and organ transplantation data were extracted from the Japan Organ Transplant Network website. RESULTS: We received questionnaire responses from 177 centers (response rate, 86%). In 2020, the number of brain-dead donors (BDDs) decreased to 68 (69% of the year-on-year average) and the number of donors after cardiac death (DCDs) decreased to 9 (32% of the year-on-year average). Eighty-five (48%) transplant centers (heart, n = 0; lung, n = 0; liver, n = 4; kidney, n = 78; pancreas, n = 22; and small intestine, n = 0) suspended transplant surgeries in response to the COVID-19 pandemic. Consequently, the number of organ transplantations from deceased donors was significantly lower in 2020 than in 2019. CONCLUSION: Although the COVID-19 pandemic has had less impact in Japan than in other countries, it has affected transplantation activity significantly, suspending transplantation surgeries in 48% of the transplantation centers, including 78% of the kidney transplantation centers, and reducing the number of organ donations to 61% of the year-on-year average.

Analysis of risk factors for donation after circulatory death kidney transplantation in Japan.

BACKGROUND: In Japan, donations after circulatory death kidney transplantation are widely performed due to legislation delays. The number of donations after brain death kidney transplantations is increasing, but the target remains unmet. We reviewed the outcomes of donation after circulatory death in Japan. METHODS: We analyzed 2923 deceased kidney transplantations (2239: donation after circulatory death (DCD), 684: donation after brain death (DBD)) performed in Japan from 2000 to 2019. The outcomes of the DCD and DBD groups were compared. We examined the risk factors for graft loss in the DCD group. RESULTS: The 5-year patient survival and death-censored graft survival rates of the DCD group, obtained by propensity score matching, were 93.6% and 95.2%, respectively, which were equivalent to 94.2% and 93.8%, respectively, obtained in the DBD group. Older donors (≥ 50 years) and prolonged cold ischemia time (≥ 12 h) were risk factors for graft loss; in the presence of these, graft survival was lower in the DCD group. CONCLUSIONS: Older donors and prolonged cold ischemia time reduced graft survival in the DCD group. Proper evaluation of donors and careful preparation for transplant surgery are, therefore, essential to ensure good transplant outcomes.

Feasibility of the automated column agglutination technique for titration of anti-A/B antibodies in ABO-incompatible living kidney transplantation.

INTRODUCTION: Quantitative measurement of anti-A/-B antibody titers is important during ABO-incompatible living kidney transplantation (ABOi-LKT). METHODS: We conducted a multi-institutional study to measure the antibody titers using the automated column agglutination technique (auto-CAT) and tube test (TT) method in ABOi-LKT recipients. Statistical analysis was performed to evaluate the two methods. RESULTS: We examined 111 samples from 35 ABOi-LKT recipients at four institutions. The correlation coefficient of the two methods was >0.9; the concordance rate and clinically acceptable concordance rate for the IgG titers were 60.4% and 88.3%, respectively. Perioperative status did not influence the statistical significance. Parallel changes were observed in the IgG antibody titers measured using the auto-CAT or TT technique by desensitizing therapy in time-course monitoring. CONCLUSION: Auto-CAT is comparable with the TT technique and is feasible for IgG anti-A/B antibody titration in ABOi-LKT recipients.

Current state of pancreas transplantation in Japan based on the nationwide registry.

In Japan, 437 pancreas transplantations (PTx) were carried out between 2000 and 2019. Clinical data for all PTx cases are registered in the Japan Pancreas Transplant Registry of the Japan Society for Pancreas and Islet Transplantation. Here we analyzed the registry data to describe the current status of PTx in Japan. The 437 PTx included 410 from deceased donors (407 from brain-dead and 3 from non-heart-beating donors) and 27 from living donors. We investigated the clinical characteristics of the 410 PTx from deceased donors. The rate of marginal donors using expanded donor criteria was higher in Japan than in other countries. At 1/5/10 years post-PTx, the overall survival rates were 95.8%/94.2%/88.7%, and the graft survival rates were 85.9%/76.2%/67.4% for pancreas and 93.2%/90.8%/78.2% for kidney (non-censored for death). These rates were comparable to those in other countries. When stratified by PTx category, survival was significantly better following simultaneous pancreas-kidney transplantation (SPK) compared to pancreas-after-kidney transplantation (PAK) or PTx alone (PTA). Immunological rejection was more frequently the cause of graft loss in PAK/PTA cases than in SPK cases, potentially contributing to the poorer survival in PAK/PTA. These outcomes highlight two main concerns: substantial incidence of pancreas graft loss, and inferior outcomes after PAK/PTA. Overall, PTx outcome is favorable in Japan, despite the high rate of marginal donors. To improve outcomes, it is important to prevent and manage each cause of pancreas graft loss. Overcoming the poorer survival in PAK/PTA may require new immunosuppressive protocols or allogenic islet transplantation.

Everolimus-facilitated calcineurin inhibitor reduction in Asian de novo kidney transplant recipients: 2-year results from the subgroup analysis of the TRANSFORM study.

OBJECTIVE: We analyzed the efficacy and safety of an everolimus with reduced-exposure calcineurin inhibitor (EVR+rCNI) versus mycophenolic acid with standard-exposure CNI (MPA+sCNI) regimen in Asian patients from the TRANSFORM study. METHODS: In this 24-month, open-label study, de novo kidney transplant recipients (KTxRs) were randomized (1:1) to receive EVR+rCNI or MPA+sCNI, along with induction therapy and corticosteroids. RESULTS: Of the 2037 patients randomized in the TRANSFORM study, 293 were Asian (EVR+rCNI, N = 136; MPA+sCNI, N = 157). At month 24, EVR+rCNI was noninferior to MPA+sCNI for the binary endpoint of estimated glomerular filtration rate (eGFR) < 50 ml/min/1.73 m2 or treated biopsy-proven acute rejection (27.0% vs. 29.2%, P = .011 for a noninferiority margin of 10%). Graft loss and death were reported for one patient each in both arms. Mean eGFR was higher in EVR+rCNI versus MPA+sCNI (72.2 vs. 66.3 ml/min/1.73 m2 , P = .0414) even after adjusting for donor type and donor age (64.3 vs. 59.3 ml/min/1.73 m2 , P = .0582). Overall incidence of adverse events was comparable. BK virus (4.4% vs. 12.1%) and cytomegalovirus (4.4% vs. 13.4%) infections were significantly lower in the EVR+rCNI arm. CONCLUSION: This subgroup analysis in Asian de novo KTxRs demonstrated that the EVR+rCNI versus MPA+sCNI regimen provides comparable antirejection efficacy, better renal function, and reduced viral infections (NCT01950819).