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.

A Translational Investigation of IFN-α and STAT1 Signaling in Endothelial Cells during Septic Shock Provides Therapeutic Perspectives.

Septic shock and disseminated intravascular coagulation (DIC) are known to be characterized by an endothelial cell dysfunction. The molecular mechanisms underlying this relationship are, however, poorly understood. In this work, we aimed to investigate human circulating IFN-α in patients with septic shock-induced DIC and tested the potential role of endothelial Stat1 (signal transducer and activator of transcription 1) as a therapeutic target in a mouse model of sepsis. For this, circulating type I, type II, and type III IFNs and procoagulant microvesicles were quantified in a prospective cohort of patients with septic shock. Next, we used a septic shock model induced by cecal ligation and puncture in wild-type mice, in Ifnar1 (type I IFN receptor subunit 1)-knockout mice, and in Stat1 conditional knockout mice. In human samples, we observed higher concentrations of circulating IFN-α and IFN-α1 in patients with DIC compared with patients without DIC, whereas concentrations of IFN-ß, IFN-γ, IFN-λ1, IFN-λ2, and IFN-λ3 were not different. IFN-α concentration was positively correlated with CD105 microvesicle concentrations, reflecting endothelial injury. In Ifnar1-/- mice, cecal ligation and puncture did not induce septic shock and was characterized by lesser endothelial cell injury, with lower aortic inflammatory cytokine expression, endothelial inflammatory-related gene expression, and fibrinolysis. In mice in which Stat1 was specifically ablated in endothelial cells, a marked protection against sepsis was also observed, suggesting the relevance of an endothelium-targeted strategy. Our work highlights the key roles of type I IFNs as pathogenic players in septic shock-induced DIC and the potential pertinence of endothelial STAT1 as a therapeutic target.

Outcomes of pancreas transplantation in older versus younger recipients: a comparative analysis.

PURPOSE: The feasibility of pancreas transplantation (PT) in older recipients remains a matter of debate. We examined the influence of recipient age on PT outcomes and identified the prognostic factors for older recipients. METHODS: We compared the outcomes of PT in recipients aged < 50 years (younger group; n = 285) with those in recipients aged ≥ 50 years (older group; n = 94). Prognostic factors in the older group were analyzed by a logistic regression model and the influence of recipient age on survival outcomes were analyzed using propensity score matching. RESULTS: The patient survival rate was significantly worse in the older group (P < 0.001). Patient death from infection or/and multiple organ failure or cardiac/cerebrovascular events was also more frequent in the older group than in the younger group (P = 0.012 and P = 0.045, respectively). A longer duration of diabetes was an independent risk factor of 1-year mortality in the older group. In a propensity score-matched comparison, the older recipients (n = 77) had significantly poorer survival than the younger recipients (n = 77) (P = 0.026). CONCLUSIONS: PT should be considered with appropriate caution, especially for older recipients with a long duration of diabetes.

Are the outcomes of Japanese pancreas transplantation utilizing extended-criteria donors acceptable? A propensity score matching analysis for donors <50 or ≥50 years old.

In Japan, about 30% of pancreatic transplant donors are ≥50 years old, making them "extended-criteria donors (ECDs)." We analyzed 361 cases of transplantation involving donors from the Japanese pancreas transplantation registry to evaluate the acceptability of ECDs. The patient survival rates at 1, 5, and 10 years after transplantation were 96.6%, 94.9%, and 88.3%, respectively. The survival rates of pancreas and kidney grafts at 1, 5, and 10 years were 85.3%, 74.8%, and 70.6%, and 94.2%, 90.9%, and 80.9%, respectively. Multivariate analysis revealed that no particular donor factors significantly influenced the pancreatic graft survival. Patients were divided into 2 groups: donors ≥50 years old (older group) and those <50 years old (younger group). After propensity score matching, the overall pancreatic graft survival at 1, 5, and 10 years after transplantation in the older group was 82.8%, 71.8%, and 69.5%, respectively, which was almost the same as in the younger group (84.9%, 70.2%, and 67.4%, respectively). No donor factors markedly influenced the pancreatic graft survival, and the outcomes of pancreas transplantation from ECDs ≥50 years old were comparable to those from younger donors.

A harmonized immunoassay with liquid chromatography-mass spectrometry analysis in egg allergen determination.

Food allergy is a serious health issue worldwide. Implementing allergen labeling regulations is extremely challenging for regulators, food manufacturers, and analytical kit manufacturers. Here we have developed an "amino acid sequence immunoassay" approach to ELISA. The new ELISA comprises of a monoclonal antibody generated via an analyte specific peptide antigen and sodium lauryl sulfate/sulfite solution. This combination enables the antibody to access the epitope site in unfolded analyte protein. The newly developed ELISA recovered 87.1%-106.4% ovalbumin from ovalbumin-incurred model processed foods, thereby demonstrating its applicability as practical egg allergen determination. Furthermore, the comparison of LC-MS/MS and the new ELISA, which targets the amino acid sequence conforming to the LC-MS/MS detection peptide, showed a good agreement. Consequently the harmonization of two methods was demonstrated. The complementary use of the new ELISA and LC-MS analysis can offer a wide range of practical benefits in terms of easiness, cost, accuracy, and efficiency in food allergen analysis. In addition, the new assay is attractive in respect to its easy antigen preparation and predetermined specificity. Graphical abstract The ELISA composing of the monoclonal antibody targeting the amino acid sequence conformed to LC-MS detection peptide, and the protein conformation unfolding reagent was developed. In ovalbumin determination, the developed ELISA showed a good agreement with LC-MS analysis. Consequently the harmonization of immunoassay with LC-MS analysis by using common target amino acid sequence was demonstrated.

Effects of preoperative plasma exchange therapy with albumin replacement fluid on blood coagulation in patients undergoing ABO-incompatible living-donor kidney transplantation using rotational thromboelastometry.

BACKGROUND: ABO-incompatible living-donor kidney transplantation (LDKT) requires immunotherapy and plasma exchange therapy (PEX). PEX with albumin replacement fluid reportedly decreases fibrinogen levels. However, no reports have described the effects of PEX with albumin replacement fluid on blood coagulation parameters and blood loss during the perioperative period. Therefore, we investigated the effects of preoperative PEX on blood coagulation parameters and blood loss during the perioperative period in patients undergoing ABO-incompatible LDKT as measured by rotational thromboelastometry (ROTEM®). METHODS: Twenty-eight patients undergoing LDKT were divided into the PEX group (ABO incompatible with PEX, n = 13) and non-PEX group (ABO compatible without PEX, n = 15). ROTEM® parameters, standard laboratory test parameters, bleeding volume, and transfusion volume were compared between PEX and non-PEX group. MCEplatelet, which represents platelet contribution to clot strength and where "MCE" stands for maximum clot elasticity, was calculated from the difference in MCE between EXTEM and FIBTEM. RESULTS: The bleeding volume during surgery and the intensive care unit (ICU) stay was significantly higher in the PEX than non-PEX group (p < 0.01). Maximum clot firmness (MCF) of EXTEM (MCFEXTEM), MCFFIBTEM, and MCEplatelet was significantly lower in the PEX than non-PEX group (p < 0.01). In the PEX group, the bleeding volume during surgery was very strongly correlated with the baseline MCFEXTEM and MCEplatelet, and the bleeding volume during the ICU stay was strongly correlated with the postoperative MCFEXTEM and MCEplatelet. CONCLUSIONS: These results suggest that the increased blood loss in the PEX group during surgery and the ICU stay was associated with decreased platelet contribution to clot strength as measured by ROTEM®. TRIAL REGISTRATION: UMIN-Clinical Trial Registry UMIN000018355 . Registered 21 July 2015.

Improved design of hammerhead ribozyme for selective digestion of target RNA through recognition of site-specific adenosine-to-inosine RNA editing.

Adenosine-to-inosine (A-to-I) RNA editing is an endogenous regulatory mechanism involved in various biological processes. Site-specific, editing-state-dependent degradation of target RNA may be a powerful tool both for analyzing the mechanism of RNA editing and for regulating biological processes. Previously, we designed an artificial hammerhead ribozyme (HHR) for selective, site-specific RNA cleavage dependent on the A-to-I RNA editing state. In the present work, we developed an improved strategy for constructing a trans-acting HHR that specifically cleaves target editing sites in the adenosine but not the inosine state. Specificity for unedited sites was achieved by utilizing a sequence encoding the intrinsic cleavage specificity of a natural HHR. We used in vitro selection methods in an HHR library to select for an extended HHR containing a tertiary stabilization motif that facilitates HHR folding into an active conformation. By using this method, we successfully constructed highly active HHRs with unedited-specific cleavage. Moreover, using HHR cleavage followed by direct sequencing, we demonstrated that this ribozyme could cleave serotonin 2C receptor (HTR2C) mRNA extracted from mouse brain, depending on the site-specific editing state. This unedited-specific cleavage also enabled us to analyze the effect of editing state at the E and C sites on editing at other sites by using direct sequencing for the simultaneous quantification of the editing ratio at multiple sites. Our approach has the potential to elucidate the mechanism underlying the interdependencies of different editing states in substrate RNA with multiple editing sites.

Temporal serum creatinine increase and exacerbation of tubulointerstitial inflammation during the first two months in resolving polyomavirus BK nephropathy.

AIM: Polyomavirus BK nephropathy (BKVN) is an important complication in kidney transplantation. After immunosuppressive agents are reduced, some patients experience a temporal increase in serum creatinine (sCr) before viral clearance. The histological characteristics of re-biopsies were therefore investigated to evaluate the time course of remission. METHODS: sCr was measured and urinary cytology evaluated periodically in 14 patients with biopsy-proven BKVN. Remission of BKVN was defined as re-biopsies negative for SV40 large T antigen (SV40-TAg) or for decoy cells on at least three consecutive cytology tests. Early changes in sCr were correlated with re-biopsy findings. RESULTS: Mean sCr was 1.6 ± 0.6 mg/dL at diagnosis, increasing during the first 2 months to 2.6 ± 2.0 mg/dL, and decreasing thereafter, to 2.3 ± 1.2 mg/dL at 3-4 months. Two patients who experienced further increases in sCr at 3 months showed early graft loss, while the others showed clinical or histological remission. Nineteen re-biopsies were obtained from eight patients over 4 months. Banff i-scores were higher in re-biopsies obtained during the first 2 months than the index biopsies and re-biopsies at 2-4 months (P = 0.02). SV40-TAg positivity was common in re-biopsies during the first 2 months (10/11 biopsies), but rarer at 2-4 months (2/8 biopsies, P = 0.001). CONCLUSIONS: Temporal graft dysfunction and increased inflammation, called immune reconstitution, were observed at 2 months. Later sCr reversal is associated with remission.

A strategy for developing a hammerhead ribozyme for selective RNA cleavage depending on substitutional RNA editing.

Substitutional RNA editing plays a crucial role in the regulation of biological processes. Cleavage of target RNA that depends on the specific site of substitutional RNA editing is a useful tool for analyzing and regulating intracellular processes related to RNA editing. Hammerhead ribozymes have been utilized as small catalytic RNAs for cleaving target RNA at a specific site and may be used for RNA-editing-specific RNA cleavage. Here we reveal a design strategy for a hammerhead ribozyme that specifically recognizes adenosine to inosine (A-to-I) and cytosine to uracil (C-to-U) substitutional RNA-editing sites and cleaves target RNA. Because the hammerhead ribozyme cleaves one base upstream of the target-editing site, the base that pairs with the target-editing site was utilized for recognition. RNA-editing-specific ribozymes were designed such that the recognition base paired only with the edited base. These ribozymes showed A-to-I and C-to-U editing-specific cleavage activity against synthetic serotonin receptor 2C and apolipoprotein B mRNA fragments in vitro, respectively. Additionally, the ribozyme designed for recognizing A-to-I RNA editing at the Q/R site on filamin A (FLNA) showed editing-specific cleavage activity against physiologically edited FLNA mRNA extracted from cells. We demonstrated that our strategy is effective for cleaving target RNA in an editing-dependent manner. The data in this study provided an experimental basis for the RNA-editing-dependent degradation of specific target RNA in vivo.

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.

Pancreas transplantation: a single-institution experience in Japan.

PURPOSE: We herein report our experience with pancreas transplantation in 26 patients at a single institution in Japan between August 2001 and December 2011. METHODS: We reviewed the medical records of 26 pancreas transplantations performed in our institute. RESULTS: The early complications (within 2 weeks) included one graft venous thrombosis, one arterial thrombosis, and two reoperations for bleeding. Of the 26 pancreas transplant recipients, five lost pancreas graft function. Of 24 simultaneous pancreas-kidney recipients, three lost kidney graft function due to noncompliance. The patient, pancreas, and kidney survival rates were 100, 96 and 93 % at 1 year; 100, 80 and 93 % at 5 years; and 100, 67 and 68 % at 10 years, respectively. Of all these complications, venous thrombosis after pancreas transplantation was the most critical. CONCLUSIONS: As the largest series of pancreas transplantations in a single institution in Japan, our series yielded better results than the worldwide data recorded by the International Pancreas Transplant Registry. Routine postoperative anticoagulation therapy is not necessary for the prevention of graft thrombosis if sufficient fluid infusion is strictly controlled and the graft blood flow is frequently monitored. When graft thrombosis occurs, both early detection and appropriate intervention are extremely important if the pancreas graft is to survive.

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.

Pre-treatment Tumor Size and Tumor Growth Rate as Prognostic Predictors for Patients With Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck Treated With Nivolumab.

BACKGROUND/AIM: The prognosis of recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) is poor, although immune checkpoint inhibitors (ICIs), such as nivolumab, have been shown to prolong survival. We investigated the factors that predict the efficacy of nivolumab when selecting an appropriate treatment strategy for patients with R/M SCCHN. PATIENTS AND METHODS: Forty-four Japanese patients with R/M SCCHN treated with nivolumab between May 2017 and October 2021 were analyzed. The primary endpoint of the study was overall survival (OS). We defined pre-treatment tumor size (PTS) as the sum of the size of all measurable lesions, and tumor growth rate (TGR) as the total growth rate of the largest tumor diameter on CT scans taken to determine treatment response, divided by the interval between CT scans. Receiver operating characteristic (ROC) curves were used to identify the cutoff points of PTS and TGR for OS. Cox proportional hazards regression analysis was performed to examine the relationships between various factors, including patient characteristics, PTS, and TGR, as well as treatment outcomes. RESULTS: In multivariate analysis, Eastern Cooperative Oncology Group (ECOG) performance status (PS) score ≥1, progressive disease (PD) as best overall response (BOR), and TGR >0.60%/day were independent risk factors for poor OS in patients with R/M-SCCHN. CONCLUSION: Higher TGR, poor PS, and PD as BOR may be prognostic factors in patients with R/M SCCHN.

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.

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.

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.

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.

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.

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 the revision of the law on pancreatic transplants in Japan-An analysis of the Japanese Pancreas Transplants Registry.

BACKGROUND: In Japan, it has been about 10 years since the revision of the law on donating brain-dead organs. The present study compared the outcomes of pancreatic transplant before and after the revision of the law. METHODS: The 437 patients who had received pancreas transplantation were divided into two groups according to the time when pancreas transplantation was performed between era 1 (before the revision) and 2 (after the revision), and compared in the patient and pancreas graft survival. RESULTS: While the annual number of brain-dead donors was <10 in era 1, and this number significantly increased in era 2 to >50. This resulted in an increased number of pancreas transplantations: >30 cases per year. The comparison data after a propensity score-matched analysis revealed that the death-censored pancreatic graft survival at 1, 3, and 5 years after pancreas transplantation in era 2 was 94.9%, 92.0%, and 92.0%, which, while lacking significance, tended to be better than the values of 90.5%, 83.1%, and 78.2%, respectively, in era 1. CONCLUSIONS: The revision of the law on donating brain-dead organs increased the number of pancreas transplantations. Technical improvements in surgery due to increased experience with performing pancreas transplants may help improve pancreatic graft survival.