Normalization of impaired glucose tolerance after kidney transplantation is associated with improved ß-cell function.

Our previous study revealed that over 50% of recipients with pretransplant impaired glucose tolerance (IGT) improved to normal glucose tolerance after kidney transplantation. However, the mechanism is unclear. We aimed to investigate whether the changes in glucose tolerance are associated with ß-cell function and insulin resistance in Japanese kidney transplant recipients with pretransplant IGT. Of the 265 recipients who received kidney transplantation, 54 with pretransplant IGT were included. We divided the recipients into improvement and nonimprovement groups according to the change in the area under the curve for glucose obtained from the oral glucose tolerance test (OGTT). ß-Cell function was estimated by the insulin secretion sensitivity index-2 (ISSI-2) and the disposition index (DI). Insulin resistance was estimated by the Matsuda index (MI) and the homeostasis model assessment of insulin resistance (HOMA-IR). ISSI-2 and DI increased significantly after transplantation in the improved group (P < 0.01, P < 0.05, respectively), but not in the nonimproved group. ΔISSI-2 and ΔDI were significantly and positively associated with pretransplant 60-min OGTT plasma glucose levels (both P < 0.01). There were no differences in MI or HOMA-IR between these two groups after transplantation. In recipients not on pretransplant dialysis, a significant negative association was found between Δblood urea nitrogen (BUN) and ΔDI (correlation coefficient = -0.48, P < 0.05). In pretransplant IGT recipients, improvements in glucose tolerance after kidney transplantation were linked to improvements in ß-cell function. The higher the 60-min OGTT plasma glucose level, the greater the improvement in posttransplant ß-cell function. Improvements in BUN after transplantation were associated with improvements in ß-cell function.NEW & NOTEWORTHY In recipients with pretransplant impaired glucose tolerance, improvements in glucose tolerance after kidney transplantation were associated with improvements in ß-cell function. The higher the pretransplant 60-min OGTT plasma glucose level, the greater the improvement in posttransplant ß-cell function. Although glucose tolerance is known to be impaired after transplantation, the present study focused on the reason for the improvement in glucose tolerance rather than the development of posttransplantation diabetes mellitus.

Spin-Orbit-Lattice Entangled State in A_{2}MgReO_{6} (A=Ca, Sr, Ba) Revealed by Resonant Inelastic X-Ray Scattering.

The 5d^{1} ordered double perovskites present an exotic playground for studying novel multipolar physics due to large spin-orbit coupling. We present Re L_{3} edge resonant inelastic x-ray scattering (RIXS) results that reveal the presence of the dynamic Jahn-Teller effect in the A_{2}MgReO_{6} (A=Ca, Sr, Ba) family of 5d^{1} double perovskites. The spin-orbit excitations in these materials show a strongly asymmetric line shape and exhibit substantial temperature dependence, indicating that they are dressed with lattice vibrations. Our experimental results are explained quantitatively through a RIXS calculation based on a spin-orbit-lattice entangled electronic ground state with the dynamic Jahn-Teller effect taken into consideration. We find that the spin-orbit-lattice entangled state is robust against magnetic and structural phase transitions as well as against significant static Jahn-Teller distortions. Our results illustrate the importance of including vibronic coupling for a complete description of the ground state physics of 5d^{1} double perovskites.

Protocol biopsy of kidney allograft enables early detection of BK virus nephropathy to preserve kidney allograft function.

BACKGROUND: The Banff Working Group has updated the histological classification of BK virus nephropathy (BKVN), highlighting the importance of early detection. However, an early detection strategy for BKVN using biopsy has not yet been established. Our investigation aimed to assess the efficacy of protocol biopsy for the diagnosis of BKVN. METHODS: We performed a retrospective cohort study of 314 patients who had undergone kidney transplantation between 2006 and 2021. Kidney allograft biopsies were performed as part of a protocol biopsy at 3 months and 1 year post-transplantation. Following the diagnosis of BKVN, the immunosuppressant dose was reduced. RESULTS: Twelve patients (3.8%) were diagnosed with BKVN by biopsy. Most diagnoses are established during the early stages of BKVN (polyomavirus nephropathy class 1 in six, class 2 in five, and class 3 in one). Following the reduction in immunosuppressant dose, kidney allograft function did not deteriorate in any patients. Additionally, test for BK virus DNA in the blood was negative. All but one patient demonstrated histological resolution of BKVN, and the other had a very slight positivity for the simian virus 40 large T antigen. The median follow-up time after BKVN diagnosis was 6 years. One patient developed de novo donor-specific antibody and subclinical acute antibody-mediated rejection that was successfully cured. CONCLUSIONS: Our analysis indicates that protocol biopsy may enable the early detection of BKVN, resulting in the preservation of kidney function.

Prophylactic bilateral nephrectomy and preemptive kidney transplantation for Denys-Drash syndrome prior to development of kidney failure.

BACKGROUND  : Nephropathy in Denys-Drash syndrome (DDS) develops within a few months of birth, often progressing to kidney failure. Wilms tumors also develop at an early age with a high rate of incidence. When a patient does not have Wilms tumor but develops kidney failure, prophylactic bilateral nephrectomy, and kidney transplantation (KTX) is an optimal approach owing to the high risk of Wilms tumor development. In the case presented here, prophylactic bilateral nephrectomy and KTX were performed in a patient who had not developed Wilms tumor or kidney failure. However, the treatment option is controversial as it involves the removal of a tumor-free kidney and performing KTX in the absence of kidney failure. CASE DIAGNOSIS/TREATMENT: We present the case of a 7-year-old boy, born at 38 weeks gestation. Examinations at the age of 1 year revealed severe proteinuria and abnormal internal and external genitalia. Genetic testing identified a missense mutation in exon 9 of the WT1 gene, leading to the diagnosis of DDS. At the age of 6 years, he had not yet developed Wilms tumor and had grown to a size that allowed him to safely undergo a KTX. His kidney function was slowly deteriorating (chronic kidney disease (CKD) stage 3), but he had not yet developed kidney failure. Two treatment options were considered for this patient: observation until the development of kidney failure or prophylactic bilateral nephrectomy with KTX to avoid Wilms tumor development. After a detailed explanation of options to the patient and family, they decided to proceed with prophylactic bilateral nephrectomy and KTX. At the latest follow-up 4 months after KTX, the patient's kidney functioned well without proteinuria. CONCLUSION: We performed prophylactic bilateral nephrectomy with KTX on a DDS patient who had not developed kidney failure or Wilms tumor by the age of 7 years. Although the risk of development of Wilms tumor in such a patient is unclear, this treatment may be an optimal approach for patients who are physically able to undergo KTX, considering the potentially lethal nature of Wilms tumor in CKD patients.

Longitudinal mortality risks and kidney functional outcomes in Japanese living kidney donors.

OBJECTIVES: Previous studies suggested that living kidney donors do not have a higher risk of death or kidney failure than the general population. However, living kidney donor risk is controversial. Furthermore, only a few studies have evaluated long-term kidney function after kidney donation. METHODS: This study evaluated Japanese kidney donor' long-term outcomes, including mortality and kidney function. From 1965 to 2015, 230 donors (76 males, 154 females, and a median age of 54) were enrolled in this study. The median observation period was 11.0 (range, 0.3-41.0) years. RESULTS: In total, 215 donors were still alive, and 15 had died. Causes of death included malignancies, cardiovascular disease, pneumonia, suicide, gastrointestinal bleeding, and kidney failure. Actual donor survival rates at 10, 20, and 30 years were 95.3%, 90.7%, and 80.9%, respectively. These values were comparable to age- and gender-matched expected survival. Long-term kidney function after donation was evaluated in 211 donors with serum creatinine data. Two donors developed kidney failure 24 and 26 years post-donation, respectively. The percentage of donors whose estimated glomerular filtration rate (eGFR) remained ≥45 mL/min/1.73 m2 at 10, 20, and 30 years after donation were 84.2%, 73.0%, and 63.9%, respectively. Survival rates of donors with eGFR <45 mL/min/1.73 m2 were comparable to those in persons with eGFR >45 mL/min/1.73 m2. CONCLUSION: Our findings revealed that kidney donors did not have a higher long-term risk of death than the general population. Although some donors showed decreased kidney function after donation, kidney function did not impact their survival.

Banff Human Organ Transplant Transcripts Correlate with Renal Allograft Pathology and Outcome: Importance of Capillaritis and Subpathologic Rejection.

BACKGROUND: To seek insights into the pathogenesis of chronic active antibody-mediated rejection (CAMR), we performed mRNA analysis and correlated transcripts with pathologic component scores and graft outcomes. METHODS: We utilized the NanoString nCounter platform and the Banff Human Organ Transplant gene panel to quantify transcripts on 326 archived renal allograft biopsy samples. This system allowed correlation of transcripts with Banff pathology scores from the same tissue block and correlation with long-term outcomes. RESULTS: The only pathology score that correlated with AMR pathways in CAMR was peritubular capillaritis (ptc). C4d, cg, g, v, i, t, or ci scores did not correlate. DSA-negative CAMR had lower AMR pathway scores than DSA-positive CAMR. Transcript analysis in non-CAMR biopsies yielded evidence of increased risk of later CAMR. Among 108 patients without histologic CAMR, 23 developed overt biopsy-documented CAMR within 5 years and as a group had higher AMR pathway scores (P=3.4 × 10-5). Random forest analysis correlated 3-year graft loss with elevated damage, innate immunity, and macrophage pathway scores in CAMR and TCMR. Graft failure in CAMR was associated with TCMR transcripts but not with AMR transcripts, and graft failure in TCMR was associated with AMR transcripts but not with TCMR transcripts. CONCLUSIONS: Peritubular capillary inflammation and DSA are the primary drivers of AMR transcript elevation. Transcripts revealed subpathological evidence of AMR, which often preceded histologic CAMR and subpathological evidence of TCMR that predicted graft loss in CAMR.

[A Case of Testicular Cancer with Solitary Iliac Bone Metastasis].

A 23-year-old male was aware of pain around his left hip joint and visited a nearby orthopedic clinic. Swelling of the right testis was pointed out, and a testicular tumor was suspected. He was referred to the urology department of a local hospital. Blood analysis showed an increase of α-fetoprotein (AFP) (3,620 ng/ml). Computed tomographic (CT) -scan revealed a left iliac bone metastasis and morbid fracture. Right radical inguinal orchiectomy was performed. The pathological examination revealed mixed germ cell tumor (embryonic carcinoma and immature teratoma: 70%, seminoma: 30%). The diagnosis was non-seminomatous germ cell tumor, stage IIIc, and poor risk on the International Germ Cell Consensus Classification. After one cycle of a bleomycin, etoposide and cisplatinum (BEP) regimen, he was referred to our hospital. After a total of 4 cycles of BEP, AFP was normalized. Denosumab was also administered monthly. The CT-scan showed a reduction of bone metastasis and recovery of ossification. Bone biopsy did not show viable tumor cells. Because extirpation of the remaining mass would require resection of the left part of the pelvic bone with significant functional loss of the left limb, we performed close follow-up after an additional 2 courses of the etoposide and cisplatin regimen. The patient is currently alive without recurrence at 45 months after the last systemic chemotherapy.

Objective evaluation of laparoscopic surgical skills in wet lab training based on motion analysis and machine learning.

BACKGROUND: Our aim was to build a skill assessment system, providing objective feedback to trainees based on the motion metrics of laparoscopic surgical instruments. METHODS: Participants performed tissue dissection around the aorta (tissue dissection task) and renal parenchymal closure (parenchymal-suturing task), using swine organs in a box trainer under a motion capture (Mocap) system. Two experts assessed the recorded movies, according to the formula of global operative assessment of laparoscopic skills (GOALS: score range, 5-25), and the mean scores were utilized as objective variables in the regression analyses. The correlations between mean GOALS scores and Mocap metrics were evaluated, and potential Mocap metrics with a Spearman's rank correlation coefficient value exceeding 0.4 were selected for each GOALS item estimation. Four regression algorithms, support vector regression (SVR), principal component analysis (PCA)-SVR, ridge regression, and partial least squares regression, were utilized for automatic GOALS estimation. Model validation was conducted by nested and repeated k-fold cross validation, and the mean absolute error (MAE) was calculated to evaluate the accuracy of each regression model. RESULTS: Forty-five urologic, 9 gastroenterological, and 3 gynecologic surgeons, 4 junior residents, and 9 medical students participated in the training. In both tasks, a positive correlation was observed between the speed-related parameters (e.g., velocity, velocity range, acceleration, jerk) and mean GOALS scores, with a negative correlation between the efficiency-related parameters (e.g., task time, path length, number of opening/closing operations) and mean GOALS scores. Among the 4 algorithms, SVR showed the highest accuracy in the tissue dissection task ([Formula: see text]), and PCA-SVR in the parenchymal-suturing task ([Formula: see text]), based on 100 iterations of the validation process of automatic GOALS estimation. CONCLUSION: We developed a machine learning-based GOALS scoring system in wet lab training, with an error of approximately 1-2 points for the total score, and motion metrics that were explainable to trainees. Our future challenges are the further improvement of onsite GOALS feedback, exploring the educational benefit of our model and building an efficient training program.

Increased urinary exosomal SYT17 levels in chronic active antibody-mediated rejection after kidney transplantation via the IL-6 amplifier.

Chronic active antibody-mediated rejection (CAAMR) is a particular problem in kidney transplantation (KTx), and ~25% of grafts are lost by CAAMR. Further, the pathogenesis remains unclear, and there is no effective cure or marker. We previously found that a hyper NFκB-activating mechanism in non-immune cells, called the IL-6 amplifier, is induced by the co-activation of NFκB and STAT3, and that this activation can develop various chronic inflammatory diseases. Here, we show that synaptotagmin-17 (SYT17) is increased in an exosomal fraction of the urine from CAAMR patients, and that this increase is associated with activation of the IL-6 amplifier. Immunohistochemistry showed that SYT17 protein expression was increased in renal tubule cells of the CAAMR group. While SYT17 protein was not detectable in whole-urine samples by western blotting, urinary exosomal SYT17 levels were significantly elevated in the CAAMR group compared to three other histology groups (normal, interstitial fibrosis and tubular atrophy, and calcineurin inhibitors toxicity) after KTx. On the other hand, current clinical laboratory data could not differentiate the CAAMR group from these groups. These data suggest that urinary exosomal SYT17 is a potential diagnostic marker for CAAMR.

Motion analysis for better understanding of psychomotor skills in laparoscopy: objective assessment-based simulation training using animal organs.

BACKGROUND: Our aim was to characterize the motions of multiple laparoscopic surgical instruments among participants with different levels of surgical experience in a series of wet-lab training drills, in which participants need to perform a range of surgical procedures including grasping tissue, tissue traction and dissection, applying a Hem-o-lok clip, and suturing/knotting, and digitize the level of surgical competency. METHODS: Participants performed tissue dissection around the aorta, dividing encountered vessels after applying a Hem-o-lok (Task 1), and renal parenchymal closure (Task 2: suturing, Task 3: suturing and knot-tying), using swine cadaveric organs placed in a box trainer under a motion capture (Mocap) system. Motion-related metrics were compared according to participants' level of surgical experience (experts: 50 ≤ laparoscopic surgeries, intermediates: 10-49, novices: 0-9), using the Kruskal-Wallis test, and significant metrics were subjected to principal component analysis (PCA). RESULTS: A total of 15 experts, 12 intermediates, and 18 novices participated in the training. In Task 1, a shorter path length and faster velocity/acceleration/jerk were observed using both scissors and a Hem-o-lok applier in the experts, and Hem-o-lok-related metrics markedly contributed to the 1st principal component on PCA analysis, followed by scissors-related metrics. Higher-level skills including a shorter path length and faster velocity were observed in both hands of the experts also in tasks 2 and 3. Sub-analysis showed that, in experts with 100 ≤ cases, scissors moved more frequently in the "close zone (0 ≤ to < 2.0 cm from aorta)" than those with 50-99 cases. CONCLUSION: Our novel Mocap system recognized significant differences in several metrics in multiple instruments according to the level of surgical experience. "Applying a Hem-o-lok clip on a pedicle" strongly reflected the level of surgical experience, and zone-metrics may be a promising tool to assess surgical expertise. Our next challenge is to give completely objective feedback to trainees on-site in the wet-lab.

Development and validation of a porcine organ model for training in essential laparoscopic surgical skills.

OBJECTIVES: To develop a wet laboratory training model for learning core laparoscopic surgical skills and evaluating learners' competency level outside the operating room. METHODS: Participants completed three tasks (task 1: tissue dissection around the aorta; task 2: tissue dissection and division of the renal artery; task 3: renal parenchymal closure). Each performance was video recorded and subsequently evaluated by two experts, according to the Global Operative Assessment of Laparoscopic Skills and task-specific metrics that we developed (Assessment Sheet of Laparoscopic Skills in Wet Lab score). Mean scores were used for analyses. The subjective mental workload was also assessed (NASA Task Load Index). RESULTS: The 54 participants included 32 urologists, eight young trainees and 14 medical students. A total of 13 participants were categorized as experts (≥50 laparoscopic surgeries), eight as intermediates (10-49) and 33 as novices (0-9). There were significant differences in the Global Operative Assessment of Laparoscopic Skills and Assessment Sheet of Laparoscopic Skills in Wet Lab scores among the three groups in all three tasks. Higher NASA Task Load Index scores were observed in novices, and there were significant differences in tasks 1 (Kruskal-Wallis test, P = 0.0004) and 2 (P = 0.0002), and marginal differences in task 3 (P = 0.0745) among the three groups. CONCLUSIONS: Our training model has good construct validity, and differences in the NASA Task Load Index score reflect previous laparoscopic surgical experiences. Our findings show the ability to assess both laparoscopic surgical skills and mental workloads, which could help educators comprehend trainees' level outside the operating room. Given the decreasing opportunity to carry out pure laparoscopic surgeries because of the dissemination of robotic surgery, especially in urology, our model can offer practical training opportunities.

Magnetic Anisotropy in Divalent Lanthanide Compounds.

Complexes of trivalent lanthanides (Ln) are known to possess strong magnetic anisotropy, which enables them to be efficient single-molecule magnets. High-level ab initio calculations are reported for [LnO] (where Ln is terbium (Tb), dysprosium (Dy), or holmium (Ho)), which show that divalent lanthanides can exhibit equally strong magnetic anisotropy and magnetization blocking barriers. In particular, detailed calculations predict a multilevel magnetization blocking barrier exceeding 3000 K for a [DyO] complex deposited on a hexagonal boron nitride (h-BN) surface, bringing the expected performance of single-molecule magnets to a qualitatively new level compared to the current state-of-the art complexes.

Interplay of spin-dependent delocalization and magnetic anisotropy in the ground and excited states of [Gd2@C78]- and [Gd2@C80].

The magnetic properties and electronic structure of the ground and excited states of two recently characterized endohedral metallo-fullerenes, [Gd2@C78]- (1) and [Gd2@C80]- (2), have been studied by theoretical methods. The systems can be considered as [Gd2]5+ dimers encapsulated in a fullerene cage with the fifteen unpaired electrons ferromagnetically coupled into an S = 15/2 high-spin configuration in the ground state. The microscopic mechanisms governing the Gd-Gd interactions leading to the ferromagnetic ground state are examined by a combination of density functional and ab initio calculations and the full energy spectrum of the ground and lowest excited states is constructed by means of ab initio model Hamiltonians. The ground state is characterized by strong electron delocalization bordering on a σ type one-electron covalent bond and minor zero-field splitting (ZFS) that is successfully described as a second order spin-orbit coupling effect. We have shown that the observed ferromagnetic interaction originates from Hund's rule coupling and not from the conventional double exchange mechanism. The calculated ZFS parameters of 1 and 2 in their optimized geometries are in qualitative agreement with experimental EPR results. The higher excited states display less electron delocalization, but at the same time they possess unquenched first-order angular momentum. This leads to strong spin-orbit coupling and highly anisotropic energy spectrum. The analysis of the excited states presented here constitutes the first detailed study of the effects of spin-dependent delocalization in the presence of first order orbital angular momentum and the obtained results can be applied to other mixed valence lanthanide systems.

Neutralizing antibody responses and cellular responses against SARS-CoV-2 Omicron subvariants after mRNA SARS-CoV-2 vaccination in kidney transplant recipients.

Although the mRNA SARS-CoV-2 vaccine has improved the mortality rate in the general population, its efficacy against rapidly mutating virus strains, especially in kidney transplant recipients, remains unclear. We examined the anti-SARS-CoV-2 spike protein IgG antibody and neutralizing antibody titers and cellular immunity against B.1.1, BA.1, and BA.5 antigens in 73 uninfected kidney recipients and 16 uninfected healthy controls who received three doses of an mRNA SARS-CoV-2 vaccine. The IgG antibody titers were significantly lower in recipients than in healthy controls. Similarly, neutralizing antibody titers against three viral variants were significantly lower in recipients. When the virus was mutated, the neutralizing antibody titers decreased significantly in both groups. In cellular immunity analysis, the number of spike-specific CD8 + non-naïve T cells against three variants significantly decreased in recipients. Conversely, the frequency of spike-specific Th2 CD4 + T-cells in recipients was higher than that in healthy controls. Nineteen recipients and six healthy controls also received a bivalent omicron-containing booster vaccine, leading to increase IgG and neutralizing antibody titers in both groups. After that, eleven recipients and five healthy controls received XBB.1.5 monovalent vaccines, increasing the neutralizing antibody titers against not only XBB.1.5, but also EG.5.1 and BA.2.86 antigens in kidney recipients. Although kidney recipients did not gain sufficient immunity against Omicron BA.5 with the third dose of vaccine, humoral response against mutant SARS-CoV-2 lineages significantly increased after bivalent Omicron-containing booster vaccine and the XBB.1.5 monovalent vaccine. Therefore, it is important for kidney recipients to continue to administer updated vaccines.

A surgical instrument motion measurement system for skill evaluation in practical laparoscopic surgery training.

This study developed and validated a surgical instrument motion measurement system for skill evaluation during practical laparoscopic surgery training. Owing to the various advantages of laparoscopic surgery including minimal invasiveness, this technique has been widely used. However, expert surgeons have insufficient time for providing training to beginners due to the shortage of surgeons and limited working hours. Skill transfer efficiency has to be improved for which there is an urgent need to develop objective surgical skill evaluation methods. Therefore, a simple motion capture-based surgical instrument motion measurement system that could be easily installed in an operating room for skill assessment during practical surgical training was developed. The tip positions and orientations of the instruments were calculated based on the marker positions attached to the root of the instrument. Because the patterns of these markers are individual, this system can track multiple instruments simultaneously and detect exchanges. However due to the many obstacles in the operating room, the measurement data included noise and outliers. In this study, the effect of this decrease in measurement accuracy on feature calculation was determined. Accuracy verification experiments were conducted during wet-lab training to demonstrate the capability of this system to measure the motion of surgical instruments with practical accuracy. A surgical training experiment on a cadaver was conducted, and the motions of six surgical instruments were measured in 36 cases of laparoscopic radical nephrectomy. Outlier removal and smoothing methods were also developed and applied to remove the noise and outliers in the obtained data. The questionnaire survey conducted during the experiment confirmed that the measurement system did not interfere with the surgical operation. Thus, the proposed system was capable of making reliable measurements with minimal impact on surgery. The system will facilitate surgical education by enabling the evaluation of skill transfer of surgical skills.

Dynamical Jahn-Teller effect and antiferromagnetism in Cs3C60.

The dynamical Jahn-Teller effect on fullerene sites in insulating Cs(3)C(60) is investigated fully ab initio. The vibronic excitations of rotational type are at ≥ 65 cm(-1), while the net kinetic contribution to the Jahn-Teller stabilization energy constitutes approximately 90 meV. This means that no localization of distortions by intermolecular interactions is possible in these fullerides; therefore, free rotations of deformations take place independently on each C(60). The latter destroy the orbital ordering and establish a conventional exchange interaction between S = 1/2 on fullerene sites. The corresponding exchange model is derived and predicts the Néel temperature for A15 Cs(3)C(60) close to experiment.

Long-Term Results in Recipients of Late Conversion to a Calcineurin Inhibitor-Free Regimen with Everolimus After Kidney Transplantation.

BACKGROUND: Conversion to a calcineurin inhibitor (CNI)-free regimen in cases of CNI nephrotoxicity (CNIT) is a strategy to improve the long-term outcomes of kidney transplantation. However, the long-term results of late conversion to a CNI-free regimen using everolimus (EVR) remain uncertain. METHODS: Nine kidney transplant recipients with biopsy-confirmed CNIT were enrolled. The median time of CNIT diagnosis was 9.0 years. All recipients underwent a conversion from CNI to EVR. We evaluated the clinical outcomes, development of donor-specific antibody (DSA), the incidence of rejection, alternative arteriolar hyalinosis (aah) scores, renal function changes, and T cell responses by mixed lymphocyte reaction (MLR) assay after conversion. RESULTS: The median follow-up after conversion was 5.4 years. Currently, 7 of 9 recipients have received a CNI-free regimen for 1.6 to 9.5 years. In the other 2 recipients, one experienced graft loss due to CNIT 3.8 years after conversion, and the other had to resume CNI due to acute T cell-mediated rejection (ATMR) a year after conversion. None of the recipients developed DSA. No rejection was observed in the kidney allograft histology except for the ATMR case. Moreover, improvement in aah scores was noted in one patient. Furthermore, serum creatinine levels were stable in recipients without proteinuria before the EVR add-on. In the MLR analysis, low responses against donors were observed in stable patients. CONCLUSIONS: Late conversion to an EVR-based regimen without CNI may be a promising therapeutic strategy against CNIT, particularly for recipients without proteinuria before the EVR add-on.

Use of Mixed Lymphocyte Reaction Assay to Evaluate Immune Tolerance before Kidney Transplantation with an Immunosuppression-Free Protocol following Hematopoietic Stem Cell Transplantation from the Same Donor.

Several cases of kidney transplantation after hematopoietic stem cell transplantation (HSCT) from the same donor for end-stage renal disease have been reported. In those cases, immunosuppressive drugs were discontinued since immune tolerance was supposed to be induced. Theoretically, the recipient's immune system recognizes the kidney allograft as its own tissue with the same human leukocyte antigen (HLA) profile, and the kidney allograft will not be rejected, even without the use of immunosuppressive agents. However, almost all recipients receive immunosuppressants in the early stages after kidney transplantation owing to concerns of acute rejection. Here, we report a successful case of post-HSCT kidney transplantation without the use of immunosuppressive drugs, in which a mixed lymphocyte reaction (MLR) assay was used to evaluate immune tolerance before kidney transplantation. The patient was a 25-year-old woman. Five years prior, she developed acute myeloid leukemia and underwent HLA-half-matched peripheral blood stem cell transplantation. Thereafter, she was in remission of the acute myeloid leukemia, but 1 year later, she developed renal graft-versus-host disease. Subsequently, the patient's renal function gradually deteriorated to end-stage renal failure, and she underwent kidney transplantation with the previous stem cell donor: her mother. HLA typing of donor and recipient showed a complete chimerism in the peripheral blood. The pretransplantation complement-dependent cytotoxic crossmatch and flow cytometric T-cell crossmatch results were both negative, and HLA antibody measurements were all negative. The MLR assay revealed no T-lymphocyte reaction to the donor; therefore, immunosuppressants were not used. Two years after transplantation, the patient's serum creatinine concentration was around 0.8 mg/dL (down from 4 mg/dL before transplantation). No abnormalities were observed in a renal biopsy performed after 3 months. Our study, along with others, indicates that immune tolerance to a donor develops in post-HSCT kidney transplantation from the same donor.