Language：English   Publishing type：Research paper (scientific journal)  

Thymic involution is associated with age-related changes of the immune system. Utilizing our innovative technique of transplantation of a thymus as an isolated vascularized graft in MHC-inbred miniature swine, we have previously demonstrated that aged thymi are rejuvenated after transplantation into juvenile swine. Here we have studied the role of insulin-like growth factor (IGF) and forkhead-box protein-N1 (FOXN1) as well as bone marrow (BM) in thymic rejuvenation and involution. We examined thymic rejuvenation and involution by means of histology and flow cytometry. Thymic function was assessed by the ability to induce tolerance of allogeneic kidneys. Aged thymi were rejuvenated in a juvenile environment, and successfully induced organ tolerance, while juvenile thymi in aged recipients involuted and had a limited ability to induce tolerance. However, juvenile BM inhibited the involution process of juvenile thymi in aged recipients. An elevated expression of both FOXN1 and IGF1 receptors (IGF-1R) was observed in juvenile thymi and rejuvenated thymi. Juvenile BM plays a role in promoting the local thymic milieu as indicated by its ability to inhibit thymic involution in aged animals. The expression of FOXN1 and IGF-1R was noted to increase under conditions that stimulated rejuvenation, suggesting that these factors are involved in thymic recovery.

DOI： 10.1111/ajt.13855

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Previous attempts of α-1,3-galactocyltransferase knockout (GalTKO) pig bone marrow (BM) transplantation (Tx) into baboons have demonstrated a loss of macro-chimerism within 24 h in most cases. In order to achieve improved engraftment with persistence of peripheral chimerism, we have developed a new strategy of intra-bone BM (IBBM) Tx. Six baboons received GalTKO BM cells, with one-half of the cells transplanted into the bilateral tibiae directly and the remaining cells injected intravenously (IBBM/BM-Tx) with a conditioning immunosuppressive regimen. In order to assess immune responses induced by the combined IBBM/BM-Tx, three recipients received donor SLA-matched GalTKO kidneys in the peri-operative period of IBBM/BM-Tx (Group 1), and the others received kidneys 2 months after IBBM/BM-Tx (Group 2). Peripheral macro-chimerism was continuously detectable for up to 13 days (mean 7.7 days; range 3-13) post-IBBM/BM-Tx and in three animals, macro-chimerism reappeared at days 10, 14 and 21. Pig CFUs, indicating porcine progenitor cell engraftment, were detected in the host BM in four of six recipients on days 14, 15, 19 and 28. In addition, anti-pig unresponsiveness was observed by in vitro assays. GalTKO/pCMV-kidneys survived for extended periods (47 and 60 days). This strategy may provide a potent adjunct for inducing xenogeneic tolerance through BM-Tx.

DOI： 10.1111/ajt.13070

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The phenomenon of accommodation in recipients of blood group ABO incompatible kidney transplantation (iKTx), in which grafts survive despite the presence of blood group A or B antigen in the graft and the presence of corresponding antibodies in the recipient's blood, is not uncommon. alpha1,3-N-Acetylgalactosaminyltransferase and alpha1,3galactosyltransferase associated with the synthesis of blood group A and B antigen (A and B enzymes), respectively, were measured by a highly specific enzyme-linked immunosorbent assay in the sera and transplanted tissues of patients who underwent an ABO iKTx. Allogeneic A and B enzymes were present in the sera and tissues as well as A and B antigens in the tissues for a long period, which hitherto have never been seen in recipients prior to an iKTx. However, activities of these enzymes in the sera after an iKTx decreased in patients who experienced a serious acute antibody-mediated rejection and disappeared in patients who had an unrepairable rejection, leading to graft loss without establishment of accommodation. Our observations on the presence of allogeneic A and B enzymes in the recipients' sera should have implications in decision making for a successful iKTx.

DOI： 10.1093/glycob/cwq086

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BACKGROUND: It is generally admitted that ABO(H) blood group antigens are linked to lipids and proteins. Although glycolipids carrying ABO antigens have been well characterized in human kidneys, glycoproteins carrying ABO antigens are largely unknown, and their molecular properties remain to be elucidated. METHODS: All the blood group A antigen-linked proteins in human kidney could be solubilized and captured on immobilized Helix pomatia lectin that recognizes A antigens. These proteins were separated on SDS-PAGE gels. The gel pieces containing protein bands immunoreactive with anti-A antibody were excised, in-gel digested with trypsin, and analyzed by nanoLC tandem mass spectrometer. Protein candidates that carry ABO antigens were confirmed by immunoprecipitation and double-labeled immunofluorescense microscopy. RESULTS: All the glycoproteins carrying ABO antigens were found to be Asn-linked glycoproteins, and presented as multiple bands on SDS-PAGE with molecular masses ranging from 60 to 270 kDa. The protein bands were subjected for mass spectrometric analysis, which identified 121 distinct proteins with high confidence. Of the identified proteins, 55 N-glycosylated, membrane proteins were selected as glycoprotein candidates that carry ABO antigens. Among them, most abundantly expressed proteins as estimated by the number of peptide matches in the MS spectrometric analysis, such as platelet endothelial cell adhesion molecule 1, plasmalemmal vesicle-associated protein, and von Willebrand factor, were further characterized. CONCLUSIONS: Several glycoproteins were identified that represented major glycoproteins carrying ABO antigens in the human kidney, which exhibited distinct features in localization to most of vascular endothelial cells.

DOI： 10.1097/TP.0b013e31819e0054

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OBJECTIVES: Regarding the relationship between donor kidney quality and renal graft function after deceased kidney transplantation (KTx) following donation after cardiac death (DCD), the evaluation timing varies depending on the study. Evaluation of histology and changes in long-term renal graft function is limited. METHODS: A retrospective single-center study included 71 recipients who underwent 0-hour biopsy for KTx from DCD. The recipients were divided into two groups to evaluate factors related to renal graft function (study1). The two groups were categorized as stable graft function and poor graft function with the change of estimated glomerular filtration rate (eGFR) after KTx. The recipients were then divided into four groups to assess whether the factors identified in study1 were related to the change in long-term renal graft function (study2). They were categorized as follows: Improved, Stable, Deteriorated, and Primary non-function with the change of eGFR after KTx. RESULTS: In study1, donor age ≥ 50 years (29.5% vs. 65.2%; p = 0.09), banff arteriolar hyalinosis (ah) score (0.66 ± 0.78 vs. 1.2 ± 1.0; p = 0.018), and presence of glomerulosclerosis (43.2% vs. 76.2%; p = 0.017) were significant risk factors for poor long-term graft function. When the recipients were divided into four groups, the severity of ah correlated well with changes in long-term renal function. CONCLUSIONS: We can predict the shift in long-term renal graft function after KTx from DCD according to the severity of ah by 0-hour biopsy.

DOI： 10.1111/iju.15357

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Language：Japanese   Publisher：(一社)日本移植学会  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J00083&link_issn=&doc_id=20240118250002&doc_link_id=10.11386%2Fjst.58.3_189&url=https%3A%2F%2Fdoi.org%2F10.11386%2Fjst.58.3_189&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：(一社)日本泌尿器内視鏡・ロボティクス学会  

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The prognosis of patients with advanced renal cell carcinoma (RCC) has improved with newer therapies, including molecular-targeted therapies and immuno-oncology agents. Despite these therapeutic advances, many patients with metastatic disease remain uncured. Inhibition of glycogen synthase kinase-3β (GSK-3β) is a promising new therapeutic strategy for RCC; however, the precise regulatory mechanism has not yet been fully elucidated. MicroRNAs (miRNAs) act as post-translational regulators of target genes, and we investigated the potential regulation of miRNAs on GSK-3β in RCC. We selected nine candidate miRNAs from three databases that could potentially regulate GSK-3β. Among these, hsa-miR-4465 (miR-4465) was downregulated in RCC cell lines and renal cancer tissues. Furthermore, luciferase assays revealed that miR-4465 directly interacted with the 3' untranslated region of GSK-3β, and Western blot analysis showed that overexpression of miR-4465 significantly decreased GSK-3β protein expression. Functional assays showed that miR-4465 overexpression significantly suppressed cell invasion of A498 and Caki-1 cells; however, cell proliferation and migration were suppressed only in Caki-1 and A498 cells, respectively, with no effect on cell cycle and apoptosis. In conclusion, miR-4465 regulates GSK-3β expression but does not consistently affect RCC cell function as a single molecule. Further comprehensive investigation of regulatory networks is required in this field.

DOI： 10.3390/cimb45090470

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Language：Japanese   Publisher：(一社)腎癌研究会  

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Language：Japanese   Publisher：(一社)腎癌研究会  

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Language：Japanese   Publisher：(一社)腎癌研究会  

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Language：Japanese   Publisher：(一社)腎癌研究会  

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Language：Japanese   Publisher：(一社)腎癌研究会  

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Language：Japanese   Publisher：(一社)腎癌研究会  

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BACKGROUND: Cytomegalovirus (CMV) infection is one of the most important infectious diseases affecting recipients of kidney transplantation (KTx). However, the timing of seroconversion for CMV infection in seronegative recipients remains unclear. We evaluated CMV infections in CMV-seronegative recipients and the time to acquire antibodies against CMV. METHODS: We conducted a retrospective study of 228 recipients who underwent KTx between March 1988 and February 2018 at the Niigata University Hospital. The anti-CMV IgG antibody profile before and after transplantation was analyzed. Oral acyclovir or valganciclovir was used as prophylactic therapy for at least 6 months after transplantation. Cytomegalovirus infection was defined as CMV viremia detected using the CMV pp65 antigenemia assay. RESULTS: In this study, 50 cases (21.9%) were CMV-seronegative recipients. Over a median follow-up period of 126.7 months, 68% (34/50) of CMV-seronegative recipients experienced CMV viremia or overt disease symptoms as the first episode of CMV infection. The median duration from transplant to CMV infection was 69.0 days (range, 22-7426). All the recipients who experienced CMV infections acquired seroconversion. The median duration from KTx to seroconversion was 7.2 months (range, 2.8-252.3). Almost all CMV-seronegative recipients could acquire anti-CMV IgG antibodies within 2.5 years. In seronegative recipients whose donors were seronegative, no CMV viremia was found, and none developed anti-CMV IgG antibodies. CONCLUSIONS: In the clinical practice of CMV-seronegative recipients, we should consider that physicians must closely monitor the occurrence of CMV infection up until 2.5 years after KTx.

DOI： 10.1016/j.transproceed.2023.03.007

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Language：English   Publisher：(一社)日本泌尿器科学会総会事務局  

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INTRODUCTION: Cytomegalovirus (CMV) is well established to be an independent risk factor for graft loss after kidney transplantation (KTx). Monitoring for CMV in the chronic phase is not defined in the current guideline. The effects of CMV infection, including asymptomatic CMV viremia, in the chronic phase are unclear. METHODS: We performed a single-center retrospective study to investigate incidence of CMV infection in the chronic phase, defined as more than 1 year after KTx. We included 205 patients who received KTx between April 2004 and December 2017. The CMV pp65 antigenemia assays to detect CMV viremia were continuously performed every 1-3 months. RESULTS: The median duration of the follow-up was 80.6 (13.1-172.1) months. Asymptomatic CMV infection and CMV disease were observed in 30.7% and 2.9% in the chronic phase, respectively. We found that 10-20% of patients had CMV infections in each year after KTx which did not change over 10 years. The history of CMV infection in the early phase (within 1 year after KTx) and chronic rejection were significantly associated with CMV viremia in the chronic phase. CMV viremia in the chronic phase was significantly associated with graft loss. DISCUSSION: This is the first study to examine the incidence of CMV viremia for 10 years post KTx. Preventing latent CMV infection may decrease chronic rejection and graft loss after KTx.

DOI： 10.3389/fcimb.2023.1190794

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BACKGROUND: The aim of this study was to determine the appropriate body mass index (BMI) in Japanese kidney transplant (KTx) recipients. We analyzed the effects of pre- and post-transplant (Tx) obesity on graft and patient survival, perioperative complications, post-transplant diabetes mellitus (PTDM), and cardiovascular disease (CVD) in Japanese KTx recipients. METHODS: This retrospective study included 269 recipients who underwent KTx from 2008 through 2020 at Niigata University Hospital. Obesity was defined as a body mass index (BMI) ≥25 kg/m2. We examined the association between pre- and post-Tx obesity and graft survival, patient survival, the incidence of PTDM and CVD, and perioperative surgical complications. RESULTS: The graft survival rate was lower in the pre-Tx BMI ≥25 kg/m2 group, although there was no significant difference in patient survival. There was no difference in graft and patient survival between the post-Tx BMI ≥25 kg/m2 group and the <25 kg/m2 group. A pre-Tx BMI ≥25 kg/m2 was an independent risk factor for biopsy-proven allograft rejection. New-onset DM after transplantation was significantly more common in the BMI ≥25 kg/m2 group than in the BMI <25 kg/m2 group (36% vs 13%; P = .002). The incidence of CVD was significantly higher in the post-Tx BMI ≥30 kg/m2 group than in the BMI <30 kg/m2 group (50% vs 11%; P = .023). There were no differences in surgical operating time, intraoperative blood loss, or perioperative complications between the obese and non-obese groups. CONCLUSION: Pre-Tx BMI ≥25 kg/m2 may be a risk factor for allograft rejection and graft loss. Post-Tx BMI should be <25 kg/m2 to reduce the risk for PTDM.

DOI： 10.1016/j.transproceed.2022.10.058

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Immune checkpoint inhibitors (ICI) have dramatically changed the treatment of metastatic renal cell carcinoma (mRCC). Although many studies have reported biomarkers as predicting the efficacy of ICI in mRCC, they remain controversial and have challenges to apply in real-world practice. We evaluated prognostic significance of multiple molecules associated with tumor immunity in patients treated with ICI. The molecules were detected in tumor tissues by immunohistochemical staining. We identified CD8-positive T cells and CD68-positive macrophages infiltrating into the tumor tissue as significant favorable prognostic factors for ICI treatment. Conversely, high expression of CD4-positive T cells was associated with poor response to ICI. Furthermore, we demonstrated that scoring for the expression status of these three molecules provides a remarkably accurate biomarker in patients with mRCC. Even the classical approach of immunohistochemistry could predict the outcome of ICI treatment by assessing the combined status of tumor-infiltrating immune cells.

DOI： 10.1038/s41598-022-24437-6

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Language：Japanese   Publisher：(一社)日本移植学会  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J00083&link_issn=&doc_id=20221028010394&doc_link_id=%2Fcl8isoke%2F2022%2Fs057s1%2F157%2F0324-0324%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcl8isoke%2F2022%2Fs057s1%2F157%2F0324-0324%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(一社)日本移植学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一社)腎癌研究会  

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Language：Japanese   Publisher：(一社)腎癌研究会  

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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BACKGROUND: As the number of long-term survivors after organ transplantation increases, malignancy has become a problem as a late complication. We herein report a case of endometrial cancer during the follow-up of pancreas transplantation after kidney transplantation. CASE PRESENTATION: A 49-year-old woman was diagnosed with endometrial cancer. The patient had developed type 1 diabetes at 8 years old and started insulin treatment, and at 29 years old, she started hemodialysis for diabetic nephropathy. At 31 years old, she received living donor kidney transplantation and withdrew from dialysis. Hypoglycemia unawareness began to occur frequently from around 36 years old, and at 48 years old, the patient underwent deceased donor pancreas transplantation after kidney transplantation and achieved insulin independence. At 49 years old, she was diagnosed with endometrial cancer. Surgical treatment (total abdominal hysterectomy with left salpingo-oophorectomy) was performed. The pathologic diagnosis was confirmed as stage 1A uterine endometrioid carcinoma grade 1. The postoperative course was uneventful. She was discharged from our hospital on postoperative day 8. There has been no evidence of recurrence and/or metastasis of endometrial cancer for 16 months since the surgery. CONCLUSIONS: Carcinogenesis after pancreas transplantation may be a lethal late complication. It is important to carry out regular screening examinations with carcinogenesis in mind.

DOI： 10.1016/j.transproceed.2021.12.021

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BACKGROUND: Although monofilament mesh-based repair is a safe and effective procedure for incisional hernia (IH) in organ transplant patients, there is no definite evidence of IH treatment for patients with graft rejection and enhanced immunosuppressive therapy. We report a successful case of large IH repair using an autologous thigh muscle fascia sheet in a kidney transplant patient. CASE PRESENTATION: A 69-year-old man had IH from the incision of kidney transplantation, which was performed 6 years ago. He had a large right lower abdominal distension hanging down to the inguinal portion. A computed tomography scan revealed a large IH with a maximum abdominal defect diameter of 15 cm. The hernia sac contained the intestine, colon, and transplanted kidney, which had pulled out along with the retroperitoneum and protruded into the abdominal wall. He had chronic active acute antibody-mediated rejection, which required frequent steroid pulse therapy and additional or adjusted immunosuppressive drugs. After total circumferential exposure of the hernia sac and abdominal fascia, the abdominal wall defect was closed using a horizontal mattress suture. The sutured line was covered with a thigh muscle fascia sheet harvested from the patient's right femur and attached to the closed fascia. He was discharged on postoperative day 13 without any complications, and no IH recurrence was observed 10 months after surgery. CONCLUSIONS: Hernia repair using autologous tissue could be a treatment option for post-transplant IH with a higher risk of infection.

DOI： 10.1016/j.transproceed.2021.09.076

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Language：Japanese   Publisher：(一社)日本臓器保存生物医学会  

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We herein report the case of a 20 year-old-man who developed bronchiolitis obliterans after living-donor renal transplantation. The patient presented with dyspnea on exertion and wheezing two years after renal transplantation, and spirometry showed an obstructive pattern. Surgical lung biopsy revealed subepithelial fibrosis that constricted and obstructed the intrabronchiolar space. Based on these findings, the patient was diagnosed with bronchiolitis obliterans. He was prescribed bronchodilators and azithromycin, and he achieved stable respiratory function for two years. The differential diagnosis of respiratory symptoms after renal transplantation includes opportunistic infection and drug-induced lung injury; however, bronchiolitis obliterans should also be considered.

DOI： 10.1016/j.resinv.2020.12.003

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会  

(背景)アルドステロンは高血圧のみならず,心機能障害や腎機能障害の原因になるとされる.慢性血液透析患者の中に著明な高アルドステロン血症を呈する症例が存在し,移植腎への影響が懸念される.腎移植後のアルドステロンの長期的な変化や移植患者への影響は不明な点が多い.(対象と方法)当院で1996年から2018年に施行された210名の患者の腎移植前後の血漿レニン活性(PRA)と血漿アルドステロン濃度(PAC)を後方視的に評価した.(結果)腎移植前は60%の症例でPRAは基準値より高値を示し,腎移植後も60%の症例が高レニン血症だった.腎移植後の高レニン血症は,アンギオテンシン受容体阻害薬(ARB)やアンギオテンシン変換酵素阻害薬(ACEI)を使用していた患者で有意に多かった.また,60%の症例で腎移植前のPACが基準値より高かったが,そのほとんどが腎移植後に自然に改善していた.腎移植後のPRA,PACの値と移植腎機能,年齢,収縮期および拡張期血圧に有意な相関はなかった.腎移植後PAC基準範囲内と高値の2群比較を行い,PAC高値群(n=29)は,拡張期血圧が有意に高く,レニン-アンギオテンシン-アルドステロン(RAAS)系阻害薬の使用が有意に少なかった.(結語)腎移植後に高アルドステロン血症が持続する患者にはRAAS系阻害薬の使用を考慮し,長期的な移植腎や心血管系への影響を観察する必要はある.(著者抄録)

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BACKGROUND: Our initial studies utilizing a galactosyl-α1-3-galactosyltransferase gene knockout (GalTKO) pig-to-baboon renal transplant model demonstrated that the early development of nephrotic syndrome has been a significant obstacle to the long-term survival of baboon recipients. We have recently documented that sphingomyelin phosphodiesterase-3 (SMPDL3b) and CD80 expressed on podocytes in porcine kidney grafts contribute to this complication. We have hypothesized that one regulator of immune function is CD47 and that incompatibilities in CD47 between pig and baboon could potentially affect macrophage function, increasing the susceptibility of the kidney grafts to immunologically induced injury. METHODS: In order to address this hypothesis in vitro, we isolated and cultured porcine podocytes and ECs from GalTKO alone, human CD47 (hCD47)/hCD55 expressing transgenic (Tg) GalTKO swine, and GalTKO hCD46/hCD55 Tg swine along with baboon or human macrophages. RESULTS: We found that baboon macrophages phagocytosed porcine ECs in a similar manner to human macrophages, and this response was significantly reduced when porcine ECs and podocytes expressed hCD47/hCD55 but not hCD46/hCD55 without hCD47. Furthermore, masking hCD47 by anti-hCD47 antibody on hCD47/hCD55Tg ECs restored phagocytosis. These results are consistent with the hypothesis that CD47 incompatibility plays an important role in promoting macrophage phagocytosis of endogenous cells from the transplanted kidney. CONCLUSIONS: The similar levels of phagocytosis of porcine cells by baboon and human macrophages suggest that the expression of hCD47Tg on glomerular cells in donor porcine kidneys may prove to be a key strategy for preventing proteinuria following kidney xenotransplantation in a pig-to-human as well as a pig-to-baboon model.

DOI： 10.1111/xen.12549

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Language：Japanese   Publishing type：Research paper (scientific journal)  

(Background) It has become evident in recent year that aldosterone has a pathogenic role in hypertension, heart failure and renal disease. Elevation of aldosterone occurs in a certain fraction of hemodialysis patients, and the adverse effects of hyperaldosteronism could pose a problem after kidney transplantation. Long-term effects of aldosterone level in renal transplant recipients remain unknown. (Materials and methods) All recipients underwent transplantation between 1996 and 2018 in Niigata university hospital were included in the study. Plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were retrospectively analyzed in 210 recipients before and after kidney transplantation. (Results) Sixty percent of recipients had higher PRA than normal upper limit before and after transplantation. The use of angiotensin receptor blocker (ARB) or angiotensin-converting-enzyme inhibitor (ACEI) was significantly more frequent in the patients with hyperreninemia than those without one after transplantation. Sixty percent of recipients had higher PAC than normal upper limit before transplantation and it spontaneously decreased to normal level after transplantation in most of them. There was no significant correlation between PAC and blood pressure, recipient age, and renal graft function after transplantation. We divided the patients into two groups, with and without post-transplant hyperaldosteronemia. The patients with post-transplant hyperaldosteronemia (n=29) had higher diastolic blood pressure and less use of renin-angiotensin-aldosterone system (RAAS) inhibitors than those with normal PAC level. (Conclusions) The use of RAAS inhibitors should be considered in post-transplant hyperaldosteronemia patients to control blood pressure and to save their long-term renal graft and heart function.

DOI： 10.5980/jpnjurol.111.74

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A 68-year-old male patient received a living donor kidney transplantation 8 years earlier for end-stage kidney disease secondary to IgA nephropathy. His post-transplantation follow-up had been routinely performed with laboratory examinations, ultrasound, and computed tomography (CT). His kidney graft function had been excellent and stable, as shown by a baseline serum creatinine level of 1.0 mg/dL. At referral, regular follow-up ultrasound and CT showed allograft hydroureteronephrosis. He did not have any complaints, but his physical examination revealed right inguinal bulging that was 3.5 × 3.5 cm. Abdominal enhanced CT revealed transplant allograft hydroureteronephrosis due to ipsilateral herniation of ureteroneocystostomy into the right inguinal canal. His serum creatinine level was slightly elevated (1.1 mg/dL). Then, he underwent an open right inguinal hernia repair. Paraperitoneal allograft hydroureteronephrosis and bladder herniation was confirmed at surgery, and hernioplasty with polypropylene mesh reinforcement was successfully performed. The postoperative course was uneventful. He was discharged on the seventh day after surgery. Six weeks after surgery, CT revealed disappearance of allograft hydroureteronephrosis and no sign of inguinal hernia recurrence with the serum creatinine stable at 1.0 mg/dL. Transplant ureteral obstruction due to inguinal hernia is a rare complication after kidney transplantation. However, transplant ureter or bladder herniation should be considered in the differential diagnosis of graft hydroureteronephrosis for preventing allograft loss.

DOI： 10.1016/j.transproceed.2020.02.131

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Glycogen synthase kinase-3 beta (GSK-3β), a serine/threonine kinase, has been identified as a potential therapeutic target in human bladder cancer. In the present study, we investigated the antitumor effect of a small molecule GSK-3β inhibitor, 9-ING-41, currently in clinical studies in patients with advanced cancer, in bladder cancer cell lines. We found that treatment with 9-ING-41 leads to cell cycle arrest, autophagy and apoptosis in bladder cancer cells. The autophagy inhibitor chloroquine potentiated the antitumor effects of 9-ING-41 when tested in combination studies. Our findings also demonstrate that 9-ING-41 enhanced the growth inhibitory effects of gemcitabine or cisplatin when used in combination in bladder cancer cells. Finally, we found that 9-ING-41 sensitized bladder cancer cells to the cytotoxic effects of human immune effector cells. Our results provide a rationale for the inclusion of patients with advanced bladder cancer in clinical studies of 9-ING-41.

DOI： 10.1038/s41598-019-56461-4

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Language：Japanese   Publisher：日本尿路結石症学会  

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Hepatitis E virus (HEV) infection has been recognized as an acute condition. However, recent reports have shown that immunocompromised patients, such as those receiving solid-organ transplantation, can develop chronic hepatitis with HEV infection. We report two cases of chronic hepatitis E after kidney transplantation (KT) who were successfully treated with ribavirin monotherapy. Several years after KT, both patients had sustained elevations in the levels of liver enzymes for a period of more than 6 months. Both patients had HEV infection, genotype 3a. Histological studies showed infiltration of inflammatory cells without fibrosis. Treatment included ribavirin monotherapy at a dosage of 600 mg daily for 3 months. One month after therapy initiation, HEV-RNA turned to negative, and remained negative at 24 weeks after ribavirin therapy without severe complications. Although the treatment of chronic hepatitis E is not fully established, ribavirin therapy can be a safe and effective treatment for chronic hepatitis E.

DOI： 10.1111/hepr.13363

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Plasma cell-rich acute rejection (PCAR) and antibody-mediated rejection (ABMR), for which a standard treatment has not yet been established, are associated with poor graft survival after kidney transplantation. Here, we report a case series of 3 Japanese patients diagnosed with PCAR accompanied by ABMR. Steroid pulse therapy and rabbit antithymocyte globulin, plasma exchange, intravenous immunoglobulin, and rituximab therapies were sequentially performed in the first case. A graft biopsy after each treatment showed that plasma cell infiltration persisted. Five months after the initiation of rejection therapy, the patient was subjected to bortezomib therapy, which led to the partial elimination of plasma cells from the graft. However, the graft function gradually deteriorated, and hemodialysis treatment was warranted. In the other 2 cases, the patients received the same combination of therapy including bortezomib within a short period. Graft biopsies performed subsequently showed a marked decrease in the number of infiltrated plasma cells, and stabilization of renal graft function was achieved in both cases. Bortezomib, which targets plasma cells, is a potent drug that eliminates infiltrated plasma cells from the graft in PCAR. Thus, in addition to conventional therapy comprising plasma exchange, intravenous immunoglobulin, and rituximab against ABMR, bortezomib may be necessary to administer without any delay to control PCAR.

DOI： 10.1016/j.transproceed.2019.02.038

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BACKGROUND: Brachytherapy is one of the standard treatments for localized prostate cancer (CaP). However, the feasibility of brachytherapy for renal transplant recipients (RTRs) is still uncertain. MATERIALS AND METHODS: Between August 2007 and March 2018, all patients who had undergone low-dose-rate (LDR) brachytherapy or high-dose-rate (HDR) brachytherapy for clinically localized CaP at our institution were retrospectively identified (n = 394). Of these patients, 3 had a history of renal transplantation. We reviewed all available clinical data retrospectively. RESULTS: All of the RTRs received ABO-incompatible renal grafts from their spouses and had stable renal graft function before the diagnosis of CaP. The median age at diagnosis of CaP was 65 years (range, 60-67 years). The median time between transplantation and brachytherapy was 7 years (range, 4-10 years). In all of the patients, clinical stage was cT1cN0M0. Two patients received 125I LDR-brachytherapy (dose, 145 Gy) and 1 patient was treated by 192Ir HDR brachytherapy (dose, 19 Gy in 2 fractions) combined with external beam radiation therapy of 39 Gy in 13 fractions. The median follow-up period after brachytherapy was 44 months (range, 34-50 months). During the follow-up period, none of the patients developed disease progression including biochemical recurrence or clinically significant adverse events associated with radiation therapy. CONCLUSIONS: LDR brachytherapy and HDR brachytherapy are safe and technically feasible in RTRs with CaP, and oncological outcomes in RTRs do not appear to be inferior to those of patients who did not receive renal transplant.

DOI： 10.1016/j.transproceed.2018.10.027

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BACKGROUND: The management of febrile urinary tract infection (fUTI) in patients with vesicoureteral reflux (VUR) is crucial to prevent renal scarring. Continuous antibiotic prophylaxis (CAP) is the most widely used initial treatment for VUR. However, the optimal duration of CAP is still unclear. We aimed to clarify an appropriate patient population and the optimal timing to discontinue CAP. METHODS: We reviewed the records of 247 patients with primary VUR between January 2000 and December 2015. Seventy-two patients who discontinued CAP despite persistent VUR were enrolled. Kaplan-Meier method and Cox proportional hazard model was used in statistical analysis. RESULTS: Following the discontinuation of CAP, fUTI developed in 25 patients after a median of 9 months (range 0-81). VUR resolved spontaneously in 9 out of 47 patients without recurrence during follow-up. Multivariate analysis showed bilateral VUR and duration of CAP of less than 1 year after the last fUTI were significant risk factors for recurrence. CONCLUSION: Among the risk factors examined, patients administered CAP for less than 1 year after the last fUTI and those with bilateral VUR had significantly more frequent recurrence. Our study suggests that the administration of CAP for more than 1 year after the last fUTI is beneficial in avoiding recurrent fUTI.

DOI： 10.1159/000497312

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Language：Japanese   Publishing type：Research paper (scientific journal)  

(Background) The standard treatment for recurrent immunoglobulin A nephropathy (rIgAN) after kidney transplantation (KTx) has not been established. (Methods) The results of treatment consisting of tonsillectomy and steroid pulse therapy in 20 recipients who were diagnosed as rIgAN were retrospectively analyzed. (Results) The level of proteinuria significantly decreased from 0.84±0.81 g/day to 0.27±0.31 g/day after treatment (P=0.007). Microscopic hematuria disappeared or improved in 58.3% and 66.6% of recipients 6 and 12 months after treatment, respectively. Serum creatinine levels remained stable for 5 years by the treatment, except for 3 cases of graft loss. Sixteen recipients received renal graft biopsies before and after treatment. Mesangial IgA deposition were dramatically decreased in 7 recipients (43.75%). The degree of mesangial hypercellularity, endocapillary hypercellularity, and crescents formation improved in 3 (18.8%), 6 (37.5%), and 4 (25%) recipients after treatment. (Conclusion) Steroid pulse therapy combined with tonsillectomy may be clinically and histopathologically effective treatment for rIgAN after KTx.

DOI： 10.5980/jpnjurol.110.92

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PURPOSE: The purposes of the present study were to evaluate growth rate of nonfunctioning adrenal incidentalomas (AIs) and their development to hormonal hypersecretion on follow-up. MATERIALS AND METHODS: A retrospective study was conducted from the electronic medical records. A total of 314 patients were diagnosed with adrenal tumors between 2000 and 2016. After excluding patients who had overt adrenal endocrine disorders or whose adrenal tumors were clinically diagnosed as metastatic malignancies, we investigated 108 patients with nonfunctioning AIs including characteristics, the treatment, the way of follow-up and pathology. RESULTS: Fifteen patients received immediate adrenalectomy because of the initial tumor size or patient's preference. Pathological examination revealed malignancy in 2 patients. In the remaining 93 patients, radiological examinations were performed periodically. Tumor enlargement of ≥ 1.0cm was observed in 8.6% of the patients who were followed up as nonfunctioning AIs with a median follow-up period of 61.5 months (range: 4-192). Eleven patients underwent adrenalectomy. On the pathological examinations, all of the tumors, which showed a size increase, were diagnosed as benign tumors. Regarding the followed up patients without adrenalectomy, only 2.4% of the patients had tumor enlargement during the prolonged follow-up. Furthermore, none of the patients developed hormonal hypersecretion or clinical signs such as obesity, glucose intolerance or poorly controlled hypertension. CONCLUSIONS: Tumor enlargement of AIs did not correlate with malignancy. The value of repeat radiological and hormonal examinations may be limited in the long-term follow-up of patients whose AIs are not enlarged.

DOI： 10.1590/S1677-5538.IBJU.2018.0235

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We have previously reported that co-transplantation of the kidney with vascularized donor thymus from α-1,3-galactosyltransferase gene knockout pigs with an anti-CD154 with rituximab-based regimen led to improved xenograft survival in baboons with donor-specific unresponsiveness. However, nephrotic syndrome emerged as a complication in which the glomeruli showed mild mesangial expansion with similarities to minimal change disease (MCD) in humans. Since MCD is associated with CD80 expression in glomeruli and elevated urinary excretion, we evaluated a potential role for CD80 in xenograft nephropathy. Study 1 confirmed high urinary CD80 excretion in nephrotic animals with renal xenografts showing CD80 expression in glomeruli. In Study 2, baboons receiving xenografts received CTLA4-Ig once a week from the second postoperative week or no CTLA4-Ig. The non-CTLA4-Ig group developed severe proteinuria with modest mesangial expansion with high urinary excretion of CD80 and documented CD80 expression in glomerular podocytes. All of the recipients in non-CTLA4-Ig groups had to be euthanized before POD 60. In contrast, CTLA4-Ig group showed a marked reduction in proteinuria and survived significantly longer, up to 193 days. These results demonstrate that anti-CD80 targeted therapy represents a promising strategy for reduction of proteinuria following renal xeno-transplantation with improved survival.

DOI： 10.1111/tri.13273

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DOI： 10.1097/01.tp.0000543158.20137.b0

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A 74-year-old Japanese man with a history of chronic hepatitis C and kidney transplant (KT) was administered pegylated-interferon plus ribavirin therapy. However, this therapy was ineffective. The patient was then hospitalized to receive ombitasvir (OBV) plus paritaprevir (PTV) plus ritonavir (r) antiviral combination therapy. He tested negative for the virus after 4 weeks, and completed 12 weeks of treatment. The patient ultimately achieved a sustained virological response after the 12 weeks of treatment. Cyclosporine (CyA) trough levels, during the OBV-PTV-r therapy, reached a peak within 5 days of initiating therapy, and increases in serum creatinine and total bilirubin were also observed. However, onset of irreversible nephropathy and hepatopathy were avoided by reducing the CyA dosage. The OBV-PTV-r therapy demonstrated a sufficient antiviral effect and could be safely administered postoperatively to patients having undergone KT. When a combination therapy with interferon-free, direct-acting antivirals is used in patients post-transplantation, consideration of drug-drug interactions with and monitoring CyA are of vital importance.

DOI： 10.1016/j.transproceed.2018.01.006

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DOI： 10.1016/j.transproceed.2017.12.052

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Language：Japanese   Publishing type：Research paper (scientific journal)  

(Backgrounds) The efficacy of bortezomib for chronic antibody mediated rejection (CAMR) after kidney transplantation is still obscure. (Materials and methods) CAMR were persisted in 5 recipients who were treated with plasma exchange, low dose of IVIG, steroid pulse therapy, and rituximab. 1.3 mg/m2 of bortezomib was administered on days 1, 4, 8, 11. Serum creatinine (sCr) levels, anti-HLA antibodies, and histology were analyzed. (Results) Stable sCr levels were obtained in 3 out of 5 recipients. No one lost renal graft function during follow-up periods. Anti-HLA class I antibodies were significantly decreased after bortezomib treatment, however anti-HLA class II antibodies were not changed. Histology showed no improvement at 6 months after bortezomib administration. Two recipients whose sCr levels increased during follow-up had already had interstitial fibrosis and tubular atrophy (IF/TA) in histology before bortezomib treatment. (Conclusions) The use of bortezomib after IF/TA could be detected in histology may not contribute to stabilize renal graft function in CAMR.

DOI： 10.5980/jpnjurol.109.68

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(Background) Long-term care is necessary for normal growth and development of pediatric recipients of kidney transplants. We report on our experience with pediatric kidney transplantation (KTx) during the past 19 years. (Methods) We retrospectively analyzed the data from 26 recipients who received KTx between 1996 and 2014 at Niigata University Hospital (one patient underwent two consecutive KTx during the designated period). All recipients were 16 years old or younger at the time of KTx. (Results) The graft survival rates at 1, 5, and 10 years after transplantation were 96%, 96%, and 88%, respectively. Three recipients lost the renal graft function due to graft thrombosis, antibody mediated rejection and steroid resistant rejection. Drug non-adherence was associated with rejection episodes, which led to the increasing of estimated glomerular filtration rate (eGFR) level. In addition, renal graft function was related to the growth after KTx. Eighteen recipients graduated from high school during follow-up periods and 17 recipients obtained employment. (Conclusion) Interventions promoting adherence should be implemented among pediatric recipients and parents to optimize graft survival and growth after KTx. Successful KTx contributed the high rate of social participation and employment after pediatric KTx.

DOI： 10.5980/jpnjurol.109.14

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Language：English   Publisher：WILEY  

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BACKGROUND: Successful xenotransplantation will likely depend, in part, on the induction of immunological tolerance, because the high levels of immunosuppression otherwise required would likely have unacceptable side effects. Rapid clearance of administered porcine hematopoietic stem cells by primate macrophages has hampered previous attempts to induce tolerance through mixed hematopoietic chimerism across a pig-to-primate barrier. Phagocytosis is normally inhibited by binding of cell surface protein CD47 to macrophage signal regulatory protein α receptors. However, pig CD47 has previously been shown to be ineffective in transducing signals through primate signal regulatory protein α. METHODS: Mobilized peripheral blood hematopoietic cells from transgenic swine expressing high or low levels of human CD47 were infused into conditioned baboons at 3 time points over a 9-week period. Xenogeneic peripheral blood chimerism was assessed after each infusion. Split thickness skin grafts from the hematopoietic cell donor swine were placed on recipients 5 weeks after the last cell infusion and 7 weeks after the discontinuation of all immunosuppression to test immune response. RESULTS: The level and duration of transient chimerism were substantially greater in baboons receiving hematopoietic cells from a pig expressing high levels of human CD47. Skin graft survival on high CD47 recipients was prolonged as well, in 1 case showing no signs of rejection at least 53 days after placement. CONCLUSIONS: Prolongation of transient porcine chimerism via transgenic expression of human CD47 in a primate model is associated with an immune modulating effect, leading to markedly prolonged survival of donor swine skin xenografts that may be applicable to clinical solid organ xenotransplantation.

DOI： 10.1097/TP.0000000000001267

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Background A shortage of donors poses a serious problem for organ transplantation around the world. In response, the concept of the expanded criteria donor (ECD) has been defined to include donors with traditionally less favorable characteristics. That definition has now been accepted and is being applied in kidney transplantation in the United States and Europe. However, the ECD has not yet been defined for deceased donor kidney transplantation in Japan. Patients and Methods We analyzed data on graft survival and relevant risk factors in patients who received deceased donor kidney transplants through the East Japan Branch of the Japan Organ Transplant network (n = 1051). Recipients were divided into two groups: the standard-function group (estimated glomerular filtration rate [eGFR] ≥20 mL/min/1.73 m2
n = 906) and the poor-function group (eGFR &lt
20 mL/min/1.73 m2
n = 145
Cox proportional hazards regression analysis
P &lt
.0001). Results The 10-year survival rate was significantly lower in the poor-function group than in the standard-function group (85.5% vs 22.5%
P &lt
.0001). The two groups differed significantly in recipient and donor risk for graft failure. Recipient risk factors were length of time on dialysis before renal transplantation and incidence of acute rejection after transplantation. Donor risk factors were donor category (heart death), age, history of hypertension, presence of cerebrovascular disease, mean urine output, and donor creatinine level immediately before donor nephrectomy, total ischemic time, and warm ischemic time. Conclusion Data from deceased donor transplantation should be analyzed in depth to determine which factors influence renal function after transplantation. In addition, ECD standards should be reconsidered for use in a Japanese context.

DOI： 10.1016/j.transproceed.2016.11.016

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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There have been few reports on allogeneic stem cell transplantation in patients who have previously undergone solid organ transplantation. The clinical course of such patients is not yet well recognized. Therefore, appropriate immunosuppressive prophylaxis for the rejection of a solid organ graft or for graft-versus-host disease has not yet been established. We present the case of a successful allogeneic stem cell transplantation in a patient who relapsed after a first allogeneic stem cell transplantation for myelodysplastic syndrome and who had previously undergone renal transplantation. The prophylaxis in this case for graft-versus-host disease and rejection of the transplanted kidney was mycophenolate mofetil and tacrolimus. No hyperacute rejection of the transplanted kidney was observed. However, the patient's renal function deteriorated after the cessation of the mycophenolate mofetil and the reduction of the tacrolimus. This deterioration seemed to be due to rejection with humoral immunity of donor lymphocytes, and we were able to control it by resuming the mycophenolate mofetil and local graft irradiation.

DOI： 10.1016/j.transproceed.2016.03.033

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BACKGROUND: Recruitment of cofactors in the interaction of the androgen receptor (AR) and AR ligands plays a critical role in determining androgenic/antiandrogenic effects of the AR ligand on signaling, but the functions of key cofactors, including nuclear receptor coactivator (NCOA), remain poorly understood in prostate cancer cells treated with AR ligands. METHODS: We examined prostate cancer cell lines LNCaP and VCaP expressing mutated and wild-type ARs, respectively, to clarify the significance of NCOAs in the effect of antiandrogens. Hydroxyflutamide showed antagonistic activity against VCaP and an agonistic effect on LNCaP. Bicalutamide served as an antagonist for both. We analyzed mRNA transcription and protein expression of NCOAs in these cells pretreated with dihydrotestosterone and thereafter treated with the mentioned antiandrogens. Transcriptional silencing of candidate NCOAs and AR was performed using small interfering RNA (siRNA). Cell proliferation was evaluated with MTT assay. RESULTS: LNCaP treated with bicalutamide showed an about four-fold increase in the expression of NCOA2 mRNA compared to those pretreated with dihydrotestosterone alone (P <0.01). In VCaP pretreated with dihydrotestosterone, transcriptions of NCOA2 and NCOA7 were slightly increased with bicalutamide (1.96- and 2.42-fold, respectively) and hydroxyflutamide (1.33-fold in both). With Western blotting, the expression of NCOA2 protein also increased in LNCaP cells treated with bicalutamide compared with that in control cells pretreated with dihydrotestosterone alone. Following silencing with siRNA for NCOA2, PSA levels in media with LNCaP receiving bicalutamide were elevated compared with those in non-silencing controls (101.6 ± 4.2 vs. 87.8 ± 1.4 ng/mL, respectively, P =0.0495). In LNCaP cells treated with dihydrotestosterone and bicalutamide, NCOA2-silencing was associated with a higher proliferation activity compared with non-silencing control and AR-silencing. CONCLUSION: NCOA2, which has been thought to be recruited as a coactivator, possibly plays a corepressive role in AR of prostate cancer cells when treated with antiandrogens, suggesting its potential as a therapeutic target.

DOI： 10.1186/s12885-016-2378-y

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Human glomeruli with intermediate (i-GS) and advanced (GS) sclerotic lesions as well as the normal control (Nor) were captured from laser microdissection, digested by trypsin and subjected to shotgun LC-MS/MS analysis (LTQ-Orbitrap XL). The label-free quantification was performed using the Normalized Spectral Index (SI N ) to assess the relative molar concentration of each protein identified in a sample. All the experimental data are shown in this article. The data is associated to the research article submitted to Journal of Proteomics [1].

DOI： 10.1016/j.dib.2015.05.013

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UNLABELLED: Since glomerular sclerosis frequently accompanies various glomerular diseases at the end stages, it is challenging to differentiate ubiquitous biological processes underlying this pathology from those critically involved in specific diseases. Furthermore, in-depth proteomic profile of human glomerular sclerosis remains limited. In this study, human glomeruli with intermediate (i-GS) and advanced (GS) sclerotic lesions, which were excluded from specific renal diseases and assumed to be aging-related, were laser captured from macroscopically normal cortex distant from urological carcinoma, and subjected to label-free quantitative proteomic analysis. We explicate an evident increase of membrane attack complex in i-GS and GS with an up-going tendency, which is accompanied by increasing of inhibitory regulators of alternative and terminal pathways. GO annotation and IPA pathway analysis agree to these results. Proteomic findings are validated by immunohistochemical studies which indicate that alternative and terminal pathways are positively involved in the glomerular sclerosis seen in distinct renal diseases. Furthermore, proteomic analysis also demonstrates remarkable increases of complement factor B in GS and TGF-ß1 in both GS and i-GS. Identification of complement factor B implicates that on-site activation of alternative pathway may occur in injured glomeruli and stepwise increase of TGF-ß1 suggests its contribution to the progression of glomerulosclerosis. BIOLOGICAL SIGNIFICANCE: This study provides in-depth quantitative proteomic profiles of human glomeruli with intermediate and advanced sclerotic lesions. It reveals that the over-expression of alternative and terminal pathway components is significantly involved in human glomerulosclerosis seen in distinct renal diseases. Proteomic identification of the increased TGF-ß1 provides supporting evidence for the role of podocyte apoptosis leading to human glomerulosclerosis.

DOI： 10.1016/j.jprot.2015.03.024

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UNLABELLED: Since α-1,3-galactosyltransferase knockout (GalT-KO) pigs became available, there has been an increasing interest in non-Gal natural antibody (nAb)-mediated xenograft rejection. To better understand mechanisms of non-Gal nAb-mediated rejection, a simple small animal model without gene manipulation would be extremely valuable. Here, we tested whether the Chinese tree shrew (CTS), which is a small-sized mammal that is phylogenetically close to primates, could serve as a model for discordant xenograft rejection. METHODS: Study 1: Expression of α-Gal antigens in hearts and kidneys of CTSs and rats was assessed by IB4 lectin binding. Presence of anti-Gal and anti-non-Gal IgM and IgG nAb in CTS sera was tested by FACS using Gal+ and GalTKO PBMC as well as BSA-ELISA. Study 2: Rat hearts were transplanted into CTS recipients (group 1, n = 7), and CTS hearts were transplanted in rats [n = 10; seven received no immunosuppression (group 2) and three received FK506 + leflunomide (group 3)]. RESULTS: Study 1: Both CTSs and rats had α-Gal expression in hearts and kidneys. ELISA showed CTSs do not have anti-Gal nAb, and flow cytometry indicated CTSs have anti-non-Gal IgM and IgG nAb in serum. Study 2: Rat hearts in CTSs were uniformly rejected within 35 mins, while CTS hearts in rats continued beating until day 5 without immunosuppression, and up to day 8 with immunosuppression. CONCLUSION: Rat-to-CTS heart transplantation is a discordant xenotransplant model, CTS-to-Rat heart transplantation is a concordant xenotransplant model. CTSs are valuable small animals to study mechanisms and strategies to avoid non-Gal nAb-mediated xenograft rejection.

DOI： 10.1111/xen.12211

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BACKGROUND: We have previously demonstrated that the juvenile thymus plays an essential role in tolerance induced by both renal transplantation and a short course of calcineurin inhibitors. Aged thymi have a decreased ability to induce tolerance. Luteinizing hormone-releasing hormone (LHRH) is known to pharmacologically rejuvenate the thymus in rodents. In order to develop a clinically applicable regimen of transplantation tolerance in adults, we sought to determine if thymic rejuvenation would occur with LHRH agonism in non-human primates. METHODS AND RESULTS: Thymic rejuvenation was evaluated by magnetic resonance imaging (MRI), histology, as well as in-vitro cellular and molecular tests. Four aged male hamadryas baboons underwent subcutaneous injection of a 3-month depot of Lupron (11.25mg; LI) and were followed for 3 months. Thymi increased volumetrically by MRI. After LI, thymic cellularity markedly increased within the cortical and medullary thymus. Additionally, a significant increase in the CD4(+)/CD45RA(hi+) population in the peripheral blood occurred for 50 days after LI, and flow cytometry of thymic tissue revealed a large increase in the percentage of CD4(+)/CD8(+) cells. TREC assay corroborated enhancement in thymic function. CONCLUSION: These data indicate that LI is associated with thymic rejuvenation in baboons, and further confirm that extrinsic factors play an important role in thymic rejuvenation in a non-human primate model.

DOI： 10.1016/j.trim.2014.09.001

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BACKGROUND: Various durations of survival have been observed in the xenotransplantation of life-supporting α-1,3-galactosyltransferase knockout (GalT-KO) porcine kidneys into nonhuman primates. Although others have demonstrated loss of GalT-KO-transplanted kidneys within 2 weeks, we have reported an average survival of 51 days with the cotransplantation of the kidney and vascularized thymus and an average of 29 days with the kidney alone. To determine the factors responsible for this difference in survival time, we performed xenogeneic kidney transplantations into cynomolgus monkeys with an anti-CD40L-based regimen using two different strains of GalT-KO swine, one derived from MGH miniature swine and the other obtained from Meji University. MATERIALS AND METHODS: Eight cynomolgus moneys received GalT-KO kidneys. Three kidney grafts were from Massachusetts General Hospital (MGH)-Nippon Institute for Biological Science (NIBS) GalT-KO pigs and five GalT-KO grafts were from MEIJI GalT-KO swine. All cynomolgus recipients were treated identically. RESULTS: Recipients of kidneys from the MGH GalT-KO kidneys swine, produced by nuclear transfer in Japan, survived an average of 28.7 days, whereas recipients of MEIJI GalT-KO kidneys swine survived an average of 9.2 days. Among the differences between these two groups, one potentially revealing disparity was that the MEIJI swine were positive for porcine cytomegalovirus, whereas the MGH-derived swine were negative. CONCLUSION: This is the first study comparing renal xenotransplantation from two different sources of GalT-KO swine into nonhuman primates at a single center. The results demonstrate that porcine cytomegalovirus may be responsible for early loss of GalT-KO swine kidney xenografts.

DOI： 10.1097/TP.0000000000000314

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BACKGROUND: Recent survivals of our pig-to-baboon kidney xenotransplants have been markedly shorter than the graft survivals we previously reported. The discovery of high levels of porcine cytomegalovirus (pCMV) in one of the rejected xenografts led us to evaluate whether this reduction in graft survival might be because of the inadvertent introduction of pCMV into our α1,3-galactosyltransferase gene knockout swine herd. METHODS: Archived frozen sections of xeno-kidney grafts over the past 10 years were analyzed for the presence of pCMV, using real-time polymerase chain reaction. Three prospective pig-to-baboon renal transplants using kidneys from swine delivered by cesarean section (C-section) and raised in isolation were likewise analyzed. RESULTS: Kidney grafts, from which 8 of the 18 archived samples were derived were found to be pCMV-negative, showed a mean graft survival of 48.3 days and were from transplants performed before 2008. None showed signs of disseminated intravascular coagulopathy and were lost because of proteinuria or infectious complications. In contrast, 10 of the archived samples were pCMV positive, were from kidney transplants with a mean graft survival of 14.1 days, had been performed after 2008, and demonstrated early vascular changes and decreased platelet counts. Three prospective xenografts from swine delivered by C-section were pCMV negative and survived an average of 53.0 days. CONCLUSIONS: Decreased survivals of α1,3-galactosyltransferase gene knockout renal xenografts in this laboratory correlate temporally with latent pCMV in the donor animals and pCMV in the rejected xeno-kidneys. Transmission of pCMV to swine offspring may be avoided by C-section delivery and scrupulous isolation of donor animals.

DOI： 10.1097/TP.0000000000000232

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Language：Japanese   Publishing type：Research paper (scientific journal)  

A 36-year-old female received protocol biopsy at 1 month after living donor kidney transplantation. At 3 months post-transplantation, presence of a growing cystic mass in the kidney graft which had not been detected preoperatively, was demonstrated by ultrasound and computed tomography. The patient had an abdominal pain around the graft. Percutaneous drainage and sclerotherapy with minocyclin were performed twice, but the cystic mass, nevertheless, became enlarged and the abdominal pain recurred again. Laparoscopic fenestration was then performed. Immunohistochemistry of the cystic mass wall showed that it was CD34 (-), EMA (-), Megalin (-), but D2-40 (+). These results suggested that the cystic mass was derived from lymphatic vessels, which developed into lymphocele in the graft. We concluded that lymphatic vessels could have been injured and obstructed by the protocol biopsy. This is the first report of successful laparoscopic fenestration for lymphocele in the kidney graft.

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PURPOSE: We aimed to examine the influence of donor age on living-donor kidney transplantation (KTx), particularly with regard to long-term graft survival in young recipients with aged kidney grafts. METHODS: Between 1988 and 2012, 287 living-donor KTxs were performed in our center. The recipients were divided into 3 groups according to age in years: under 30 (young), 30-49 (middle-aged), and over 50 (old). The data regarding the influence of kidneys from donors aged over 50 years were retrospectively analyzed. RESULTS: Graft survival at 1, 5, 10, and 15 years was 94.7, 94.7, 90.2, and 75.2%, respectively, in young recipients who received grafts from donors aged under 50 years, and 96.4, 91.9, 65.4, and 41.4%, respectively, in young recipients who received grafts from donors aged over 50 years (P = 0.023). In contrast, there were no significant differences regarding graft survival and donor age in the middle-aged and old recipient groups. Multivariate analysis revealed that young recipient and rejection episode were significant predictors of graft loss in transplantation from older donors. Histological examination revealed significant age-related changes in the grafts before transplant and a significant higher rate of glomerular hypertrophy at the 1-month protocol biopsy in young recipients with aged kidney grafts. CONCLUSIONS: Kidney grafts from older living donors affected long-term graft survival in young recipients. In addition to the damage from rejection, aged kidney grafts, which have less nephron mass, may have a limited capacity to appropriately respond to increases in physiological or metabolic demands of young recipients, leading to a greater reduction in renal function.

DOI： 10.1007/s11255-014-0655-8

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We previously reported life-supporting α1,3-galactosyltransferase knockout (GalTKO) thymokidney xenograft survival of >2 months in baboons. However, despite otherwise normal renal function, recipients developed proteinuria with morphologic changes (podocyte effacement), a condition that presents a major obstacle to long-term studies in this model. A recent clinical study showed that rituximab therapy after allogeneic transplant prevented proteinuria possibly associated with loss of sphingomyelin phosphodiesterase acid-like 3b (SMPDL-3b). Here, we demonstrate that rituximab prevents the disruption of pig podocytes in an SMPDL-3b-dependent manner in vitro and the early development of proteinuria after xenogeneic kidney transplantation in baboons. Immunofluorescence showed SMPDL-3b expression in pig glomerular epithelium; immunoprecipitation demonstrated rituximab binding to SMPDL-3b in glomeruli. Culture of isolated pig podocytes with naive baboon sera, which has preformed antipig natural antibodies, reduced SMPDL-3b expression, disrupted podocyte morphology, and decreased podocyte proliferation, whereas pretreatment with rituximab prevented these effects. Six baboons received rituximab before transplantation to deplete B cells and again in the peri-transplant period; 18 baboons treated only before transplantation served as historical controls. The onset of post-transplant proteinuria was significantly delayed in a B cell-independent manner in the animals that received peri-transplant rituximab treatment. Although further optimization of this protocol is required, these data provide intriguing clues to the mechanisms of post-transplant proteinuria in xenogeneic kidney transplantation and a potential strategy for its prevention.

DOI： 10.1681/ASN.2013040363

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Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：Elsevier USA  

Background Patient and graft survival after successful kidney transplantation (KT) have improved despite an increase in the number of challenging cases. Various factors have evolved during the long history of kidney transplantation. Methods Between 1988 and 2012, a total of 292 living donor and 56 deceased donor KTs were performed at Niigata University Hospital. Long-term patient and graft survival and changes in background during a 20-year period in a single center were retrospectively analyzed. Results Excellent patient survival rates of 95.1% at 20 years for living donor KT and 96.2% at 15 years for deceased donor KT were observed. Graft survival rates at 1, 5, 10, 15, and 20 years were 96.8%, 95.4%, 83.1%, 61.8%, and 56.2% in living donor KT, respectively. In contrast, graft survival rates at 1, 5, 10, and 15 years in deceased donor KT were 89.0%, 80.3%, 77.3%, and 33.8%, respectively. These survival rates have dramatically improved since 2002 (91.7% for living and 80.9% for deceased donor KT at 10 years post-transplantation). The number of elderly recipients (older than 60 years) and the percentage of grafts donated from spouses have increased. The rejection rate decreased and the cytomegalovirus antigenemia-positive rate increased during the 20-year period assessed. The percentage of pre-emptive KTs progressively increased, with graft survival in this group tending to be better than non-preemptive KTs. The causes of graft loss were chronic allograft dysfunction (54.7%), acute rejection (11.1%), and malignancies (9.4%). After living donor KT, the principal predictors of graft loss were if the recipient was younger than 30 years, if the donor was older than 50 years, and if the rejection episodes occurred after living donor KT. In contrast, the only risk factor in the case of deceased donor KT occurred after transplantation from donors who were older than 50 years. Conclusions A summary of the long-term outcome of KT over 20 years in a single center has been reported. Along with the changes in patient backgrounds, immunosuppressive drugs, and our knowledge of transplantation, patient and graft survival outcomes have also changed. Investigation into such outcomes during a different transplantation era is required to fully appreciate advances in KT. © 2014 by Elsevier Inc. All rights reserved.

DOI： 10.1016/j.transproceed.2013.10.052

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BACKGROUND: We have previously reported that Massachusetts General Hospital miniature swine, which had accepted class I-mismatched kidneys long-term after 12 days of high-dose cyclosporine A, uniformly accepted donor-major histocompatibility complex (MHC)-matched kidneys without immunosuppression but rejected donor MHC-matched split-thickness skin grafts by day 25, without changes in renal graft function or antidonor in vitro responses. We have now tested whether this "split tolerance" would also be observed for the primarily vascularized skin of vascularized composite allografts (VCAs). METHODS: Group 1 animals (n=3) received donor MHC-matched VCAs less than 70 days after primary kidney transplant (KTx). Group 2 animals (n=3) received a second donor-matched kidney transplant followed by a donor-matched VCA more than 200 days after primary KTx. RESULTS: Animals in Group 1 lost the epidermis on days 28, 30, and 40, with all other components of the VCAs remaining viable. Histology showed cellular infiltration localized to dermal-epidermal junction. One of three recipients of VCAs in Group 2, accepted all components of the VCA, including epidermis (>200 days). The other two recipients lost only the epidermis on days 45 and 85, with survival of the remainder of the VCA long-term. CONCLUSIONS: All tissues of a VCA are accepted long-term on animals tolerant of class I-mismatched kidneys, with the exception of epidermis, the survival of which is markedly prolonged compared with split-thickness skin grafts but not indefinite. Exposure of tolerant animals to second donor-matched kidneys before VCA increases the longevity of the VCA epidermis, suggesting an increase in the immunomodulatory mechanisms associated with tolerance of the kidney.

DOI： 10.1097/TP.0b013e3182a579d0

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We have previously shown that tolerance of kidney allografts across a full major histocompatibility complex (MHC) barrier can be induced in miniature swine by a 12-day course of high-dose tacrolimus. However, that treatment did not prolong survival of heart allografts across the same barrier. We have now tested the effect of cotransplanting an allogeneic heart and kidney from the same MHC-mismatched donor using the same treatment regimen. Heart allografts (n = 3) or heart plus kidney allografts (n = 5) were transplanted into MHC-mismatched recipients treated with high-dose tacrolimus for 12 days. As expected, all isolated heart allografts rejected by postoperative day 40. In contrast, heart and kidney allografts survived for >200 days with no evidence of rejection on serial cardiac biopsies. Heart/kidney recipients lost donor-specific responsiveness in cell-mediated lympholysis and mixed-lymphocyte reaction assays, were free of alloantibody and exhibited prolonged survival of donor, but not third-party skin grafts. Late (>100 days) removal of the kidney allografts did not cause acute rejection of the heart allografts (n = 2) and did not abrogate donor-specific unresponsiveness in vitro. While kidney-induced cardiac allograft tolerance (KICAT) has previously been demonstrated across a Class I disparity, these data demonstrate that this phenomenon can also be observed across the more clinically relevant full MHC mismatch. Elucidating the renal element(s) responsible for KICAT could provide mechanistic information relevant to the induction of tolerance in recipients of isolated heart allografts as well as other tolerance-resistant organs.

DOI： 10.1111/ajt.12423

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BACKGROUND: Vascular endothelial cells (VECs) play crucial roles in physiological and pathologic conditions in tissues and organs. Most of these roles are related to VEC plasma membrane proteins. In the kidney, VECs are closely associated with structures and functions; however, plasma membrane proteins in kidney VECs remain to be fully elucidated. METHODS: Rat kidneys were perfused with cationic colloidal silica nanoparticles (CCSN) to label the VEC plasma membrane. The CCSN-labeled plasma membrane fraction was collected by gradient ultracentrifugation. The VEC plasma membrane or whole-kidney lysate proteins were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis and digested with trypsin in gels for liquid chromatography-tandem mass spectrometry. Enrichment analysis was then performed. RESULTS: The VEC plasma membrane proteins were purified by the CCSN method with high yield (approximately 20 μg from 1 g of rat kidney). By Mascot search, 582 proteins were identified in the VEC plasma membrane fraction, and 1,205 proteins were identified in the kidney lysate. In addition to 16 VEC marker proteins such as integrin beta-1 and intercellular adhesion molecule-2 (ICAM-2), 8 novel proteins such as Deltex 3-like protein and phosphatidylinositol binding clathrin assembly protein (PICALM) were identified. As expected, many key functions of plasma membranes in general and of endothelial cells in particular (i.e., leukocyte adhesion) were significantly overrepresented in the proteome of CCSN-labeled kidney VEC fraction. CONCLUSIONS: The CCSN method is a reliable technique for isolation of VEC plasma membrane from the kidney, and proteomic analysis followed by bioinformatics revealed the characteristics of in vivo VECs in the kidney.

DOI： 10.1007/s10157-012-0708-1

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Language：Japanese   Publishing type：Research paper (scientific journal)  

PubMed

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Diphtheria toxin (DT)-based anti-CD3 immunotoxins have clinical relevance in numerous applications including autoimmune disease therapies and organ transplantation tolerance protocols. Pre-existing anti-DT antibodies acquired either by vaccination against diphtheria toxin or infections with C. diphtheriae may interfere or inhibit the function of these anti-CD3 immunotoxins. Previously, a full-length anti-rhesus monkey CD3 immunotoxin, FN18-CRM9, was shown to be less effective at depleting circulating T cells in animals with pre-existing anti-DT antibody titers than in animals without antibodies, and subsequent doses were ineffective. In this study, the T cell depletion function of a truncated DT based recombinant anti-monkey CD3 immunotoxin, A-dmDT390-scfbDb (C207), as part of a reduced intensity conditioning regimen prior to hematopoietic cell transplantation, was compared between two groups of monkeys: those with and without pre-existing anti-diphtheria titers. T cell depletion was comparable in both groups of monkeys, and therefore appeared to be unaffected by the presence of moderate levels of pre-existing anti-diphtheria antibodies.

DOI： 10.1016/j.trim.2012.05.003

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The lymphocyte immunosuppressant sensitivity test (LIST) with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay procedure can predict the pharmacological efficacy of immunosuppressive agents. A previous study reported the pharmacological efficacy of tacrolimus evaluated by LIST just before renal transplantation significantly correlated with the incidence of acute rejection episodes. However, the pharmacological efficacy of tacrolimus has not been estimated after renal transplantation. Therefore, the present study evaluated the pharmacological efficacy of tacrolimus by LIST using the MTT assay procedure before and 1, 3, and 12 months after transplantation in 17 renal transplant recipients that received tacrolimus-based immunosuppressive therapy. The tacrolimus pharmacological efficacies before and after the procedure were also compared with incidence of acute rejection and cytomegalovirus (CMV) infection episodes. The individual values of tacrolimus 50% inhibition of lymphocyte proliferation (IC50) varied widely before transplantation, and the mean value of the IC50 was 126.4 ± 337.7 ng/ml. The patients were divided into two groups according to the tacrolimus IC50 values evaluated before transplantation. The rate of acute rejection episodes in the tacrolimus high-sensitivity group was significantly lower than that in the tacrolimus low-sensitivity group (p = 0.005). The tacrolimus IC50 deviation between patients expanded further at one and three months after surgery. However, the sensitivity deviation almost converged at 1 year after surgery. Moreover, the pharmacological efficacy of tacrolimus evaluated at 1, 3, and 12 months after transplantation did not significantly correlate with the incidence of acute rejection episodes. The pharmacological efficacies of tacrolimus evaluated at both before and after surgery were not significantly correlated with the episodes of CMV infection. These findings suggest that the pharmacological efficacy of tacrolimus evaluated with LIST before surgery is a useful biomarker for predicting the occurrence of acute allograft rejection in renal transplantation.

DOI： 10.3727/215517912X639360

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Basiliximab is a recently developed immunosuppressive agent for the prevention of acute allograft rejection in renal transplant recipients. The combination use of basiliximab and a calcineurin inhibitor was suggested to be more effective in comparison to immunosuppressive therapy using calcineurin inhibitor without basiliximab. Cyclosporine has been generally administered with basiliximab for renal transplant recipients. However, in cases of tacrolimus-based immunosuppressive regimen, the clinical efficacy and safety of combined use of tacrolimus and basiliximab remains to be elucidated. This study evaluated the tacrolimus pharmacological efficacy using a lymphocyte immunosuppressant sensitivity test (LIST) with MTT assay procedures in 16 cases of renal transplant recipients treated by tacrolimus without basiliximab and in 13 cases treated by tacrolimus in combination with basiliximab. The rate of acute rejection episodes in the recipients treated with tacrolimus plus basiliximab was 1/13 (7.7%), whereas the rate in the recipients treated with tacrolimus without basiliximab was 6/16 (37.5%). The recipients were divided into two groups according to their peripheral blood mononuclear cell (PBMC) sensitivity to tacrolimus [i.e., including a tacrolimus high sensitivity group (IC(50) <1.0 ng/ml) and a low sensitivity group (IC(50) >1.0 ng/ml). In the recipients treated with tacrolimus without basiliximab, the rate of acute rejection episodes in the tacrolimus high sensitivity group was 1/10 (10.0%), which was significantly lower than the rate in the low sensitivity group of 5/6 (83.3%; p = 0.008). The incidence of cytomegalovirus infection was not significantly different between the tacrolimus high and the low sensitivity groups of the recipients treated with tacrolimus with and without basiliximab. Therefore, in the case of selected tacrolimus-based immunosuppressive therapy for renal transplant recipients, the tacrolimus pharmacological efficacy should be evaluated using LIST at a time just before the transplant procedure in order to accurately predict allograft rejection. The data also suggested that low tacrolimus sensitivity recipients should be treated with tacrolimus-based immunosuppressive therapy in combination with basiliximab.

DOI： 10.3727/096368911X605493

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OBJECTIVES: Cyclosporine and tacrolimus are calcineurin inhibitors that are used to prevent acute rejection in renal transplant recipients. The lymphocyte immunosuppressant sensitivity test (LIST) can predict the pharmacological efficacy of these immunosuppressive agents for renal transplant recipients. There is a correlation between cyclosporine and tacrolimus pharmacological efficacy as evaluated by LIST by the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay procedure prior to renal transplantation. However, the LIST can also evaluate patients before and after the transplantation. MATERIALS AND METHODS: The present study examined the relationship between cyclosporine and tacrolimus pharmacological efficacy by LIST using the MTT assay in 16 renal transplant recipients at 1, 3 and 12 months after transplantation, as well as before the operation. RESULTS: The relationship of cyclosporine and tacrolimus pharmacological efficacy gave a significant Kendall and Spearman's coefficient correlation in these transplant recipients by the LIST using the MTT assay procedure immediately prior to renal transplantation (rk = 0.711, rs = 0.877, p < 0.01). Furthermore, correlations between the cyclosporine and tacrolimus IC50 values were also observed with a significant Kendall and Spearman's coefficient correlation at 1 and 12 months after transplantation (rk1month = 0.65, rs1month = 0.829, p < 0.01, and k12month = 0.433, rs12month = 0.603, p < 0.01, respectively). However, no statistically significant relationship was observed between the pharmacological efficacies of the calcineurin inhibitors at 3 months after transplantation (rk3month = 0.117, rs3month = 0.1, p > 0.05). CONCLUSIONS: Both cyclosporine and tacrolimus exhibit pharmacological efficacy by the inhibition of calcineurin. However, the correlation between cyclosporine and tacrolimus pharmacological efficacies may be altered, due to immunosuppressive therapy or clinical events at 3 months after renal transplantation.

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Language：Japanese   Publisher：一般社団法人 日本泌尿器科学会  

DOI： 10.5980/jpnjurol.102.125_1

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BACKGROUND: We have recently reported that perioperative low-dose carbon monoxide (CO) inhalation decreases lung ischemia-reperfusion injury in miniature swine. The aims of this study were to establish a large animal model of pulmonary allograft rejection using polymerase chain reaction-typed major histocompatibility complex (MHC)-inbred CLAWN miniature swine and to examine the effects of CO on allograft survival. METHODS: Eleven CLAWN miniature swines received fully MHC-mismatched lungs followed by 12 days of tacrolimus (days 0-11; blood level 35-45 ng/mL). Six recipients received tacrolimus alone (control group). Five recipients were additionally treated with inhaled CO (180 min for donors until graft harvest; 390 min for recipients until 2 hr after reperfusion). RESULTS: All recipients treated with tacrolimus alone uniformly rejected their grafts by postoperative day 63 with development of cytotoxic antidonor antibodies. CO treatment was effective in prolonging allograft survival from a mean of 47±7 to 82±13 days (P=0.017), with one CO-treated animal maintaining function until postoperative day 120. Development of antidonor antibodies and donor-specific responsiveness by cell-mediated lympholysis and mixed lymphocyte reaction assays was delayed in animals that received CO therapy. Furthermore, serum concentrations of proinflammatory cytokines (interleukin-1β and -6) 1 day after transplant were significantly decreased in the CO-treated group. CONCLUSIONS: Fully MHC-mismatched lungs in CLAWN miniature swine were consistently rejected within 63 days, suggesting that this is a robust large animal model ideal for investigating mechanisms and treatment of lung rejection. Perioperative low-dose CO inhalation prolonged graft survival and inhibited antidonor antibody production and was associated with decreased proinflammatory mediators in this model.

DOI： 10.1097/TP.0b013e3181ff8730

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The lymphocyte immunosuppressant sensitivity test (LIST) can predict the pharmacological efficacy of immunosuppressive agents. We herein estimated the mycophenolic acid efficacy using LIST before and 1, 3, and 12 months after the operation in 15 renal transplant recipients. The pharmacological efficacy of mycophenolic acid as assessed before transplantation showed small individual variations, whereas the variability greatly increased at 1 and 3 months after transplantation. Furthermore, the individual IC50 variation among these subjects at 1-year after operation was closely similar to that observed before surgery. No significant implications of these individual differences in the mycophenolic acid sensitivity were noted in regard to the clinical courses of these recipients.

DOI： 10.3109/08923970903490478

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At the age of three yr, a male patient had surgical treatment for bilateral vesicoureteral reflux (VUR), and at the age of 19 yr, he developed nephrotic syndrome because of focal segmental glomerulosclerosis (FSGS). His renal function deteriorated despite treatment with temocapril and aspirin, and dialysis treatment was started when he was 19. After nine yr of dialysis, he received a living kidney transplantation from his 58-yr-old father, who had a long history of hypertension. A graft biopsy before perfusion showed moderate arteriolosclerosis. As urine protein increased to 2.15 g/d at 16 months after kidney transplantation, the graft biopsy was performed again. FSGS lesion with severe arteriosclerosis was recognized under light microscope, while the effacement of podocyte foot processes was seldom observed. The alteration of calcineurin inhibitor from cyclosporine to tacrolimus, combined with the new administration of angiotensin receptor antagonist (valsartan) and aldosterone receptor blocker, successfully decreased the amount of urine protein to 0.8 g/d within two wk. We considered that the present case showed two distinct types of FSGS lesions--one because of VUR and the other because of cyclosporine arteriolopathy--in each native kidney and transplanted kidney.

DOI： 10.1111/j.1399-0012.2010.01267.x

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Nonocclusive mesenteric ischemia (NOMI) is an infrequent and fatal disorder. We describe a 54-year-old man who developed NOMI during the peritransplant period following ABO-incompatible living-donor kidney transplantation, but who was successfully treated with his renal graft function unimpaired. Abdominal pain appeared on the sixth postoperative day (POD), and emergency surgery was performed on POD 8. Discontinuous segmental necrosis extended throughout the small intestine, and the necrotic segments were entirely removed. He thereafter had ischemia of the ascending colon, which was treated with colectomy, and prostaglandin E1 delivered through the related artery prevented advanced necrosis. Temporary colostomy was closed 20 months after surgery. He maintains excellent graft function at present without secondary disorder. There has been no ABO-incompatible kidney transplant recipient complicated with NOMI. However, patients with end-stage renal disease are at the highest risk for this lethal condition, and physicians and urologists should correctly recognize its diagnostics and therapeutics.

DOI： 10.1007/s10157-009-0232-0

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DOI： 10.1097/TP.0b013e3181c89307

PubMed

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OBJECTIVE: Lymphocyte immunosuppressant sensitivity test (LIST) is useful for predicting the pharmacological efficacy of immunosuppressive agents. In this study, the pharmacological efficacy of cyclosporine was estimated by LIST before and after renal transplantation. METHODS: Lymphocyte immunosuppressant sensitivity test was performed by the 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide (MTT) assay before and at 1, 3, and 12 months after transplantation in 19 consecutive renal transplant recipients. RESULTS: There was wide intersubject variability in cyclosporine IC50 before transplantation [Mean (SD) of 593.9 (1067.6) ng/mL]. This variability worsened 1 month after transplantation [525.7 (1532.7) ng/mL] but decreased at 3 months (193.5 (347.9) ng/mL) and 12 months (75.4 (95.4) ng/mL). In this small study, observed differences in IC50 values for the individual subjects at various time intervals was not associated with the occurrence of rejection, graft loss, and infection episodes. CONCLUSION: Lymphocyte sensitivity to cyclosporine assessed by the LIST assay showed a high level of inter-subject variability particularly before and 1 month after transplantation. The observed difference in IC50 values was not associated with clinical outcome in this small study.

DOI： 10.1111/j.1365-2710.2009.01036.x

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AIM: To find novel genes abundantly and preferentially expressed in human glomerulus, we constructed a glomerular cDNA library and verified the reliability of our database by comparison with the Stanford Microarray Database (SMD), followed by reverse transcription polymerase chain reaction (RT-PCR) and in situ hybridization (ISH). METHODS: RNA was extracted from normal human glomeruli, and the cDNA library was constructed by plasmid cloning. Out of 5 x 10(3) clones from the library, 91 UniGene clusters of more than three clones were identified as 'glomerular-abundant genes'. All these genes were referred to the SMD, and 18 genes were defined as 'glomerular preferential genes'. Four unknown genes -IFI27, CRHBP, FLJ10154 and SEMA5B- were selected for RT-PCR to compare expression in the glomerulus with that in the cortex and medulla, and for ISH to examine glomerular localization. Also, three unknown genes that were glomerular abundant but not listed in the SMD -DDX5, HSPC138, and MGC10940- were selected for RT-PCR and ISH. Finally, a kidney biopsy specimen of crescentic glomerulonephritis was used for ISH to examine glomerular expression for CRHBP mRNA. RESULTS: Among the selected seven glomerular-abundant genes, six were confirmed as 'glomerular preferential genes' by RT-PCR. By ISH, all these genes were demonstrated in podocytes. The expression of CRHBP mRNA in a single living podocyte was not changed between normal and crescentic glomerulus. CONCLUSION: Glomerular preferential expression and podocyte localization of these novel genes have been demonstrated for the first time. Because some of these genes were not listed in SMD, our database can be a useful tool to find novel human glomerular genes.

DOI： 10.1111/j.1440-1797.2008.01009.x

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The lymphocyte immunosuppressant-sensitivity test (LIST) has been reported extensively as being able to estimate the pharmacological efficacy of immunosuppressive drugs in individual patients. This study measured the IC50 values for 6 drugs, cyclosporine, tacrolimus, methylprednisolone, 6-mercaptopurine, mycophenolic acid, and mizoribine, against mitogen-induced proliferation of peripheral-blood lymphocytes in 29 renal transplant recipients. We also examined relationship between the IC50 values and 4 factors; age, duration of dialysis, percentage of lymphocytes in total white blood cells, and blastogenesis stimulation index by mitogen. There were no significant correlations between the IC50 values and these factors, except that the tacrolimus IC50 value was correlated weakly with the stimulation index (p<0.05, r=-0.429). It was concluded that the pharmacological efficacy of immunosuppressive drugs cannot be inferred from the patient characteristics or their laboratory data. LIST is an effective method to elucidate the pharmacodynamic properties of immunosuppressive agents in individual renal transplant recipients without being influenced by the recipient clinical data.

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The kidney glomerulus plays a pivotal role in ultrafiltration of plasma into urine and also is the locus of kidney disease progressing to chronic renal failure. We have focused proteomic analysis on the glomerulus that is most proximal to the disease locus. In the present study, we aimed to provide a confident, in-depth profiling of the glomerulus proteome. The glomeruli were highly purified from the kidney cortex from a male, 68-year-old patient who underwent nephroureterectomy due to ureter carcinoma. The patient was normal in clinical examinations including serum creatinine and urea levels and liver function, and did not receive any chemotherapy and radiotherapy. The cortical tissue was histologically normal, and no significant deposition of immunoglobulins and complement C3 was observed. We employed a novel strategy of protein separation using 1D (SDS-PAGE) and 2D (solution-phase IEF in combination with SDS-PAGE) prefractionation prior to the shotgun analysis with LC-MS/MS. The protein prefractionation produced 90 fractions, and eventually provided a confident set of identified proteins consisting of 6686 unique proteins (3679 proteins with two or more peptide matches and 3007 proteins with one peptide match), representing 2966 distinct genes. All the identified proteins were annotated and classified in terms of molecular function and biological process, compiled into 1D and 2D protein arrays, consisting of 15 and 75 sections, corresponding to the protein fractions which were defined by MW and pI range, and deposited on a Web-based database (http://www.hkupp.org). The most remarkable feature of the glomerulus proteome was a high incidence of identification of cytoskeleton-related proteins, presumably reflecting the well-developed, cytoskeletal organization of glomerular cells related to their physiological functions.

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Endometriosis of the urinary tract is uncommon. We report a case of bilateral ureteral endometriosis. A 46-years-old woman was presented with facial edema. The level of blood urea nitrogen and creatinine were 52 and 4.83 mg/dl respectively at the first examination. Retrograde urography demonstrated bilateral hydronephrosis with distal ureteral obstruction and MRI (magnetic resonance imaging) showed left ovarian cyst. CA125 level was 93 U/ml. We diagnosed the case as ureteral endometriosis by exploratory laparotomy. After 16 month of gonadotropin-releasing hormone analogue therapy and ureteral dilation with catheter, she underwent end-to-side uretero-ureterostomy with ureteral reimplantation (psoas hitch). Bilateral hydronephrosis and renal function were improved after the operation. The case was suspected of extrinsic type ureteral endometriosis.

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We report a case of retroperitoneal gas gangrene, which was caused by cecal diverticulitis with perforation. A-57-year-old male was admitted to the Sado General Hospital with the chief complaint of right lateral abdominal pain. Roentogenogram and Computelized Tomography (CT) showed gas accumulation in the retroperitoneal space behind the ascending colon. Based on the clinical, labolatory, and instrumental examination findings gas gangrene was diagnosed. Since urolithiasis or urinary tract infection was suspected to be the cause of the lesion at that time, the patient was transferred to our department immediately. CT scan done on day 3 at our inpatient department provided data suspicious for the cecal perforation into retroperitoneal space due to appendicitis or diverticulitis. We performed an acute drainage of the abscess and intensive care including continuous hemodiafiltration (CHDF), oxygen under high pressure (OHP), and chemotherapy with antibiotics was carried out. However, in spite of the above mentioned measures, the patient's condition deteriorated and he died due to progression of gangrene and multiple organ failure in 23 days. The autopsy revealed that the cause of perforation was cecal diverticulitis. Retroperitoneal gas gangrene is an uncommon entity and has been rarely reported. It is supposed that laparotomy with diagnostic and therapeutic purpose should have been performed in this case.

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Language：Japanese   Publisher：(一社)日本移植学会  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J00083&link_issn=&doc_id=20220106290002&doc_link_id=10.11386%2Fjst.56.3_195&url=https%3A%2F%2Fdoi.org%2F10.11386%2Fjst.56.3_195&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：(一社)日本臨床腎移植学会  

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Language：Japanese   Publisher：(一社)日本臨床腎移植学会  

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Language：Japanese   Publisher：日本腎泌尿器疾患予防医学研究会  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会  

(背景)アルドステロンは高血圧のみならず,心機能障害や腎機能障害の原因になるとされる.慢性血液透析患者の中に著明な高アルドステロン血症を呈する症例が存在し,移植腎への影響が懸念される.腎移植後のアルドステロンの長期的な変化や移植患者への影響は不明な点が多い.(対象と方法)当院で1996年から2018年に施行された210名の患者の腎移植前後の血漿レニン活性(PRA)と血漿アルドステロン濃度(PAC)を後方視的に評価した.(結果)腎移植前は60%の症例でPRAは基準値より高値を示し,腎移植後も60%の症例が高レニン血症だった.腎移植後の高レニン血症は,アンギオテンシン受容体阻害薬(ARB)やアンギオテンシン変換酵素阻害薬(ACEI)を使用していた患者で有意に多かった.また,60%の症例で腎移植前のPACが基準値より高かったが,そのほとんどが腎移植後に自然に改善していた.腎移植後のPRA,PACの値と移植腎機能,年齢,収縮期および拡張期血圧に有意な相関はなかった.腎移植後PAC基準範囲内と高値の2群比較を行い,PAC高値群(n=29)は,拡張期血圧が有意に高く,レニン-アンギオテンシン-アルドステロン(RAAS)系阻害薬の使用が有意に少なかった.(結語)腎移植後に高アルドステロン血症が持続する患者にはRAAS系阻害薬の使用を考慮し,長期的な移植腎や心血管系への影響を観察する必要はある.(著者抄録)

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Language：Japanese   Publisher：(一社)日本腎臓学会  

移植後に起こる移植関連血栓性微小血管症(transplantation associated thrombotic microangiopathy:TA-TMA)は、移植腎機能を喪失する可能性がある疾息として認識する必要があり、ときに早期の治療介入が必要である。腎移植後のTA-TMAに特異的かつ統一された診断基準はなく、過去の報告は造血幹細胞移植の診断基準の一部を使用しているにすぎない。腎移植後のTA-TMAは、移植腎機能障害、血小板減少や溶血性貧血を伴うsystemic TA-TMAと、それらを伴わないlocalized TA-TMAに大きく分類される。前者は進行が急速で予後不良とされるため、これらを含む報告では移植腎予後は30〜50%程度とされる。後者は進行が緩徐であるが、TMAのない群と比較すると移植腎生着率は有意に低いとされる。腎移植後TA-TMAの病因による分類として、再発性TA-TMAとそれ以外のde novo TMAとに分けられる。再発性TA-TMAに大きく関係しているのが補体遺伝子異常を原因とする非典型溶血性尿毒症症候群(aHUS)である。De novo TA-TMAの原因として、薬剤(カルシニューリン阻害薬やmTOR阻害薬)、抗体関連型拒絶反応、ABO血液型不適合移植、ウイルス感染症、虚血再潅流障害、補体遺伝子異常などがTMAのトリガーとなる可能性が報告されている。治療として、aHUSの場合は血漿交換とエクリズマブの使用、抗体関連型拒絶反応の場合は血漿交換、ステロイドパルス療法、大量免疫グロブリン静注療法やリツキシマブの使用などが行われる。それ以外の場含は、関連がある薬剤の減量や中止、ウイルス感染症の治療(免疫抑制薬の減量、中止)などを検討する。腎移植後TA-TMAは迅速な対応が必要であるため、診断、治療の決定に必要な検査や治療の院内体制を確認しておくことが重要である。(著者抄録)

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Language：Japanese   Publisher：(一社)日本臨床腎移植学会  

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Language：Japanese   Publisher：(一社)日本臨床腎移植学会  

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Language：Japanese   Publisher：(一社)日本臨床腎移植学会  

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Language：Japanese   Publisher：(一社)日本臨床腎移植学会  

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Language：Japanese   Publisher：(一社)日本臨床腎移植学会  

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Language：Japanese   Publisher：(一社)日本臨床腎移植学会  

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Language：Japanese   Publisher：新潟医学会  

終末期医療の中で臓器提供はその一部に過ぎないが、最近は臓器提供そのものがグリーフケアの一環として考えられ、位置づけられつつある。移植外科医は脳死下臓器摘出からドナーの終末期医療に直接関与し、ドナーの尊い意志、それを尊重しようとする家族の思いを直接レシピエントに届ける直接的な役割を担っている。移植を成功させ臓器の生着を得ることがレシピエント救命のための最大の目的であるが、ドナー家族にとっても移植の成否は重要である。後日送られるレシピエント本人からのサンクスレターを通して、臓器提供への感謝や、移植の成功がドナー家族に直接伝達されることのグリーフケアとしての意義は大きい。脳死下臓器摘出とその後の搬送、レシピエント手術のそれぞれの過程において、現場での細かい注意点や遵守すべきルールがある。移植外科医は医学的な判断のみならず、礼位の保持をはじめ、その場に応じた適切な対応と果たすべき役割を認識して行動する必要がある。(著者抄録)

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Language：Japanese   Publisher：新潟医学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY  

DOI： 10.5687/iscie.32.294

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞ポイント ・ABO不適合腎移植において術前の脱感作療法は非常に重要である.・脱感作療法の内容は患者ごとに個別化できる可能性が示唆される.・免疫学的順応のメカニズムは,補体制御蛋白の変化と抗体産生の抑制機構が関与している可能性がある.

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本補体学会  

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Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会  

(背景)腎移植後の再発性IgA腎症(recurrent IgA nephropathy:以下rIgAN)の標準的治療法は未だ確立していない。(対象と方法)原発性IgA腎症による末期腎不全に対して腎移植術を施行されたレシピエントのうち、移植腎生検にてrIgANと診断された20症例を対象とし、扁桃腺摘出術とステロイドパルス併用療法の効果について後方視的に解析を行った。(結果)尿蛋白については、治療前が0.84±0.81g/day、治療後が0.27±0.31g/dayと治療により有意に尿蛋白は改善していた(P=0.007)。顕微鏡的血尿は治療半年後、1年後でそれぞれ58.3%、66.6%の患者が消失もしくは改善していた。血清クレアチニン値は、移植腎機能喪失した3症例を除いて、治療後5年間で有意な変化は見られず安定していた。治療前後で移植腎生検を施行し得た16症例のうち、7例(43.75%)の患者でメサンギウム領域のIgAの沈着が消失もしくは著明に減弱していた。また、メサンギウム細胞増多、管内細胞増多、半月体形成などの急性期病変は治療によりそれぞれ3例(18.8%)、6例(37.5%)、4例(25%)の患者で改善していた。(結論)移植後rIgANに対する扁桃腺摘出術とステロイドパルス併用療法は臨床的にも組織学的にも有用である可能性が示唆された。(著者抄録)

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本臨床腎移植学会  

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Language：Japanese   Publisher：(一社)日本臨床腎移植学会  

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Language：Japanese   Publisher：(一社)日本臨床腎移植学会  

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Language：Japanese   Publisher：医学図書出版(株)  

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J-GLOBAL

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Language：Japanese   Publisher：(一社)日本臨床腎移植学会  

ABO式血液型不適合腎移植(以下、ABO不適合腎移植)は、減感作療法の開発・発展に伴って成績向上してきたと言っても過言ではない。血漿交換が抗体関連型拒絶反応に効果的だったことが報告されてから、ABO不適合腎移植前に抗体除去を行い、脾臓を摘出することで成績が向上することがAlexandreらにより1987年に報告されたのが減感作療法の始まりと言える。それ以来、抗体除去法の検討、リツキシマブによる脾摘の回避やカルシニューリン阻害薬のB-1 B細胞の抑制などが報告され、減感作療法は少しずつ変遷していった。2000年以前は、抗体価が64倍以上の症例は移植腎生着率が有意に悪かったが、2001年以降、抗体価による移植腎生着率の差はなくなった。これも、減感作療法の発達によるものと言える。近年では、超高抗体価に対するABO不適合腎移植の成功症例の報告や、減感作療法を症例により省略する報告も散見されるようになった。これからの課題は高抗体価症例に対する減感作療法の安全性の基準や、低抗体価症例に対する減感作療法の省略の基準を明確にすることである。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J06262&link_issn=&doc_id=20181213470003&doc_link_id=%2Fem0sfcrt%2F2018%2F000602%2F003%2F0139-0145%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fem0sfcrt%2F2018%2F000602%2F003%2F0139-0145%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：長岡赤十字病院  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本補体学会  

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Language：Japanese   Publisher：(一社)腎癌研究会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

DOI： 10.1097/01.tp.0000543276.46991.4b

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

DOI： 10.1097/01.tp.0000543287.07980.0b

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

DOI： 10.1097/01.tp.0000543456.88760.cc

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

DOI： 10.1097/01.tp.0000543594.62792.27

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Language：Japanese   Publisher：(株)東京医学社  

腎移植の成績と悪性腫瘍の発生について検討した。1988〜2015年末に当施設で腎移植を実施した416例(生体腎移植320例、献腎移植96例)を対象とした。レシピエントの移植時年齢中央値は38.5歳、男性272例、女性144例、ドナー年齢の中央値は55.0歳であった。1・5・10・15・20年後の患者生存率は生体腎99.4、97.8、95.6、93.4、82.0%、献腎97.1、92.6、87.4、84.1、84.1%、死亡症例は24例(5.8%)であった。全416例中29例(7%)に32件の悪性腫瘍が発生した。悪性腫瘍あり群29例と非悪性腫瘍群387例を比較検討したところ、移植時年齢、性別、透析期間、生体腎移植の比率、ABO血液型不適合の比率、ドナー年齢に有意差は認められなかった。しかし、癌なし群は癌あり群と比較して有意差をもって生存・生着率が良好であった。

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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Language：Japanese   Publisher：腎移植・血管外科研究会  

【背景】移植後リンパ増殖性疾患(post-transplant lymphoproliferative desorder:PTLD)は、近年増加傾向にある。【対象と方法】当院で1988-2015年の間に行われた413症例を対象に、PTLDを発症した5症例を後方視的に検討した。【結果】男性3例、女性2例で、移植時の年齢の中央値は51歳、PTLD診断時の年齢の中央値は55歳、腎移植後にPTLDと診断されるまでの期間の中央値は142ヵ月だった。5例のうち1例は死亡、3例は透析再導入となった。死亡した症例を除き、全例で免疫抑制薬の減量・中止が行われ、1例で外科的切除術、1例で化学療法、1例で両者併用が行われた。【結論】5人のPTLDのうち、4人がLate onsetであり、腎移植後の継続的なスクリーニングが必要であると考えられた。(著者抄録)

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Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(公社)日本臨床工学技士会  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会  

(目的)腎移植後の慢性抗体関連型拒絶反応(Chronic antibody mediated rejection;CAMR)に対するボルテゾミブの効果については報告が少なく、今回5症例に使用したためその結果を報告する。(対象と方法)5名の腎移植後CAMR患者に対し、初期治療として血漿交換、ガンマグロブリン静注療法、ステロイドパルス治療、リツキシマブ投与が全例で施行された。初期治療後、抗ドナーHLA抗体が陰性化せず、組織学的にCAMR残存があったため、ボルテゾミブ1.3mg/m2をday1、4、8、11の4回静脈内投与した。ボルテゾミブ投与3ヵ月後に抗HLA抗体検査、6ヵ月後に抗HLA抗体検査と移植腎生検を行い、治療効果を判定した。(結果)ボルテゾミブ投与後の移植腎機能は5例中3例で安定していたが、2例において血清クレアチニン(sCr)の継時的な上昇を認めた。ボルテゾミブ投与により抗HLA class I抗体は有意な減少を示したが、抗HLA class II抗体に関しては経過を通して有意な減少を示さなかった。また、ボルテゾミブ投与による組織学的な改善は認めなかった。移植腎機能が悪化した2症例は、治療前のsCrが高く、組織所見ですでに間質の線維化や尿細管の萎縮が存在した症例であった。(結論)臨床的、組織学的に悪化したCAMRに対し1コースのボルテゾミブ投与は、移植腎機能の安定化に寄与しない。(著者抄録)

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Language：Japanese   Publisher：(一社)日本泌尿器科学会  

(目的)小児腎不全の治療目標は生命予後の改善のみならず患児を健常児と遜色なく心身ともに健やかに成長、自立させることである。腎不全患児が安心して成人を迎えるためには5〜15年以上にわたって移植腎機能が保たれる必要がある。我々が1995年から2014年までに経験した症例につき検討し、報告する。(対象と方法)1995年12月から2014年8月までに腎移植を行い、移植時に16歳以下であった26名、27症例を対象として後方視的に検討した(1例のみ期間中に2回の移植を経験)。(結果)当院での移植腎生着率は1年、5年、10年でそれぞれ96%、96%、88%であり諸家の報告と遜色のない成績であった。腎廃絶は3例に認められ、廃絶の原因は移植腎血栓症、ステロイド抵抗性拒絶反応、抗体関連型拒絶反応だった。Drug non-adherenceは拒絶反応を高率に誘発し、その後の移植腎機能悪化に関連していた。また移植腎機能悪化は、その後の成長にも悪影響を及ぼした。移植後の就職状況は、経過観察中に18歳以上となった18例(69%)中、作業所勤務やアルバイトも含めれば17例が職に就いていた。(結論)小児腎移植において服薬指導を徹底しdrug non-adherenceを防ぎ、拒絶反応を防ぐことが長期の移植腎機能温存と移植後身長の改善に寄与すると考えられた。腎移植の成功により、患児の就職状況は良好であった。(著者抄録)

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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Language：Japanese   Publisher：(一社)日本移植学会  

症例1は20歳男性で、両側性低形成腎にて慢性腎不全のため16歳時に母親をドナーにpreemptiveでABO血液型不一致移植を行った。導入期、免疫抑制療法としてタクロリムス(FK)、メトトレキサートモフェチル(MMF)、メチルプレドニゾロン(MP)、バシリキシマブ(Bax)の4剤を用いた。移植早期、FKによる白質脳症を認めシクロスポリン(CYA)に変更した。移植後4年急激な肝酵素上昇を認め、家族がイノシシ料理を摂取し患者は摂取しなかったが同じ調理器具で調理した料理を摂取していた。4ヵ月後、肝機能は正常化しHEV RNAも陰性化した。症例2は40歳男性で、原因疾患不明の慢性腎不全で25歳時に透析導入、37歳時に母親をドナーにABO血液型不一致移植を行った。免疫抑制療法はCYA、MMF、MPの3剤で行った。移植後感染症の合併も拒絶反応も認められず、移植腎機能は良好であったが、全身倦怠感を認め、急激な肝酵素上昇を認め緊急入院した。焼肉屋で半生肉摂取の経験があり、輸液と利胆剤で肝胆道系酵素は速やかに改善し2ヵ月後に正常化し、HEV RNAも陰性化した。症例3は25歳男性で、8歳時に両側尿細管逆流症で逆流防止術を行ったが腎機能が低下し、18歳時に慢性腎不全のため、父親をドナーとしてpreemptiveでABO血液型不一致移植を行った。FTY720の治験対象症例で導入期免疫抑制療法はCYA、MMF、MP、FTY720の4剤で、移植後早期にBanff Iaの拒絶反応を認めたがステロイドパルス療法で改善した。治験中止後はFTY720以外の3剤で維持した。複数のウイルス感染症合併でMMF中止、2剤で維持した。肝逸脱酵素の急激な上昇を認め、利胆剤で経過観察したがHEV抗体陽性となり、肝生検を行いアクティブな肝炎所見を認めた。リバビリン投与で改善傾向となった。症例4は33歳男性で、26歳時に原因疾患不明の慢性腎不全で、母親をドナーにABO血液型不一致移植を行った。移植後4年、肝逸脱酵素の軽度上昇を認め、HEV RNA陽性であった。利胆剤で経過観察したが、6ヵ月後、IgG-HEV抗体/IgM-HEV抗体が陽性で、治療について検討する予定となっている。

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J00083&link_issn=&doc_id=20171214250012&doc_link_id=%2Fcl8isoke%2F2017%2F005204%2F012%2F0390-0396%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcl8isoke%2F2017%2F005204%2F012%2F0390-0396%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：(一社)日本臓器保存生物医学会  

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Language：English   Publisher：(一社)日本癌学会  

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Language：Japanese   Publisher：(一社)日本癌学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY  

Web of Science

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)腎癌研究会  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：腎移植・血管外科研究会  

移植医療におけるドナー不足は大きな問題であり、高齢者ドナーや心停止後摘出臓器の利用が世界的にも増加している。移植後の腎機能に影響する因子を検討することは以前より行われてきた。当院における59例の心停止下献腎移植の移植腎機能にかかわるレシピエント因子、ドナー因子、graft因子をそれぞれ後方視的に解析した。その結果、UNOSの定義するExpanded criteria donor(ECD)とgraft hyalinosisの程度が移植後腎機能に大きく影響する因子であることが分かった。(著者抄録)

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ELSEVIER SCIENCE INC  

DOI： 10.1016/j.juro.2017.02.251

Web of Science

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ELSEVIER SCIENCE INC  

DOI： 10.1016/j.juro.2017.02.2169

Web of Science

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J-GLOBAL

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Language：Japanese   Publisher：(株)メディカル・サイエンス・インターナショナル  

腎腫瘍の診断において、ダイナミックCTがゴールドスタンダードである。予後不良の患者を見極め、早急に専門医へ紹介する必要がある。充実性腫瘍の膨張性発育型で、ダイナミックCTの造影早期相で不均一な濃染を呈する腫瘍は、まず淡明細胞癌であると言い当てることができる。CT所見である程度の組織型まで判別できる。一方で、オンコサイトーマやfat-poor AMLなどの診断は今後の課題である。(著者抄録)

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Language：Japanese   Publisher：(一社)日本臓器保存生物医学会  

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Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Web of Science

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Web of Science

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Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：(一社)日本外科学会  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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J-GLOBAL

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Language：Japanese   Publisher：(一社)日本臨床腎移植学会  

【研究目的】世界的にドナー不足は深刻な問題となっており、欧米でも条件の悪いExpanded Criteria Donor(ECD)を定義しルールに基づき配分している。しかし、日本における献腎移植のECDの明確な指標はいまだにない。【方法】日本臓器移植ネットワーク(JOT)東日本支部における献腎移植症例を対象に、移植1年後の移植腎機能が良好に発現維持されているstandard群(Cr<2.0mg/dL、n=802)と不良であるpoor群(Cr≧2.0mg/dL、n=220)の2群に分け、生着率、そのリスクファクターを検討した。【結果】10年移植腎生着率は、standard群に比べpoor群は有意に低下していた(87.9% vs 47.2%、P<0.0001)。レシピエント要因としては、性別(男性)、透析期間、ドナー要因としては、ドナータイプ(心停止下)、年齢、高血圧の既往歴、ドナーの脳血管障害の有無、ドナー腎摘出前尿量・血圧、TIT、WITで、2群間で有意な差を認めた。【結論】献腎移植の成績を通じて、移植腎機能に影響する因子を詳細に解析するとともに日本のECDの基準を検討する必要性がある。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2015&ichushi_jid=J06262&link_issn=&doc_id=20160106350010&doc_link_id=%2Fem0sfcrt%2F2015%2F000302%2F010%2F0189-0194%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fem0sfcrt%2F2015%2F000302%2F010%2F0189-0194%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(株)医学書院  

近年,2010年7月に改正臓器移植法が施行されてから脳死下多臓器提供症例は増加している。心停止下の腎臓単独での摘出とは異なり,多臓器摘出専門チームと協力して腎臓を摘出するため,腹部内臓全般の解剖学的知識,肝臓,膵臓,小腸の摘出術式にも精通している必要性がある。本稿では,これらを踏まえた脳死下腎摘出術について,実際の現場での手順について述べる。また,脳死下献腎移植は,心停止下献腎移植と比べて温阻血時間(warm ischemic time:WIT)や総阻血時間(total ischemic time:TIT)が短いため提供腎の状態もよく,生体腎移植に比べても遜色ない成績である。しかし,その一方でgraft lossの要因にDWFG(death with functioning graft)も少なくない。東日本の脳死下献腎移植のデータから献腎移植の問題点について検討し概説する。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2015&ichushi_jid=J01561&link_issn=&doc_id=20151211080008&doc_link_id=10.11477%2Fmf.1413205505&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1413205505&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本臨床腎移植学会  

Pentraxin 3(PTX3)は炎症局所産生性の急性期炎症蛋白で、拒絶反応時に腎間質で発現が増加する。傍尿細管毛細血管のC4d沈着(C4d on PTC)は抗体関連型拒絶反応(ABMR)診断の条件だが、ABO血液型不適合(ABO-I)移植では非特異的に観察される。今回、PTX3発現が、ABO-I移植腎での組織学的ABMRの新規指標となるかを検討した。ABO-I腎移植20例(ABMR発症4例、非発症16例)を対象に、PTX3発現増加およびC4d on PTCによりABMRを診断する場合の感度・特異度を求めた。陽性所見は、PTX3はABMR群3例、非発症群0例、C4d on PTCはABMR群全例と非発症群12例でみられた。診断感度と特異度はそれぞれ、PTX3は75%と100%、C4d on PTCは100%と25%であった。PTX3発現増加は、ABO-IでのABMRの新規組織学的指標になり得ると思われた。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2015&ichushi_jid=J06262&link_issn=&doc_id=20150812480010&doc_link_id=%2Fem0sfcrt%2F2015%2F000301%2F010%2F0062-0067%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fem0sfcrt%2F2015%2F000301%2F010%2F0062-0067%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：(株)日本医学館  

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Language：Japanese   Publisher：(株)日本医学館  

ABO血液型不適合腎移植におけるaccommodationのメカニズムはいまだに解明されていない。移植腎に発現するABO血液型抗原や、抗ドナー血液型抗体の移植腎血管内皮細胞に対する親和性を解析することが、accommodationのメカニズムの解明につながるのではないかと、近年当科でも基礎研究を行っている。質量分析計を用いた解析により、腎臓に発現するABO血液型糖鎖抗原が結合する蛋白質をほぼすべて同定できた。また、ヒト由来の抗A、抗B抗体を精製し、それらの抗体の赤血球に対する凝集反応と腎臓への結合を解析している。さらに、ヒトリンパ球を培養しin vitroで抗A・抗B抗体が産生される条件を追究し、ABO不適合腎移植後の抗ドナー血液型抗体産生能の解析を行っている。(著者抄録)

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Language：Japanese   Publisher：(株)中外医学社  

透析導入年齢の高齢化が進み,腎移植を受ける患者も徐々に高齢化している.臓器不足は移植医療における最大の問題であり,高齢者を含むマージナルドナーからの移植も増加傾向にある.しかし,ドナー年齢は腎移植後の移植腎生着率に大きく影響することが知られており,レシピエントの年齢との組み合わせにより,その影響は複雑化する.近年の報告では,高齢ドナー(移植腎の加齢)は,若年層レシピエントの移植腎生着率低下に大きく影響することが生体腎移植,献腎移植双方において認められた.若いレシピエントに拒絶反応が多いとされ,また機能的ネフロン数が減少した高齢ドナーの腎臓では,期待余命の長い若いレシピエントの移植腎生着率に大きく影響していることが示唆される.期待余命の短い高齢レシピエントは,移植腎が機能したまま死亡することが多く(Death with functioning graft),"移植腎の寿命"を有効活用できていない問題もある.ドナー,レシピエントの年齢差が移植腎生着率にどのように影響するかを知ることは,腎移植の適応,ドナーの選択や移植後の管理の点で非常に重要なことである.(著者抄録)

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J-GLOBAL

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J-GLOBAL

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Language：Japanese   Publisher：(株)日本医学館  

糖尿病性腎症の腎移植における免疫抑制療法について検討した。腎移植を施行した374例中、原疾患が糖尿病性腎症(DMN)の23例を対象とした。1型DMNは9例中4例に拒絶反応を認め、3例はデオキシスパガリン(DSG)、1例はDSGに加えSTパルス療法を行った。2型DMNは14例中3例が拒絶反応を認め、DSGで治療した。DMN全体の生存率は、1年100%、5年90%、10年80%、生着率は、1年100%、5年90%、10年72%であった。導入免疫抑制療法は、2001年以降は、膵腎同時移植症例以外はシクロスポリン(CyA)+ミコフェノール酸モフェチル(MMF)+ST+バシリキシマブを導入した。維持免疫抑制療法は10例がSTを中止し、CyA+MMFの2剤で行った。13例はSTを継続した。

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Language：Japanese   Publisher：(一社)日本泌尿器内視鏡学会  

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Language：Japanese   Publisher：新潟医学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J00990&link_issn=&doc_id=20141225170038&doc_link_id=http%3A%2F%2Fhdl.handle.net%2F10191%2F43938&url=http%3A%2F%2Fhdl.handle.net%2F10191%2F43938&type=%90V%8A%83%91%E5%8Aw%81F%90V%8A%83%91%E5%8Aw%8Aw%8Fp%83%8A%83%7C%83W%83g%83%8A_Nuar&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F80230_3.gif

Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：新潟医学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J00990&link_issn=&doc_id=20141225160022&doc_link_id=%2Fdg3nigta%2F2014%2Fs12808%2F014%2F0408-0408%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdg3nigta%2F2014%2Fs12808%2F014%2F0408-0408%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会  

症例は36歳女性。母をドナーとする生体腎移植術1ヵ月後に、プロトコール移植腎生検を受けた。移植3ヵ月後の超音波検査で移植腎に嚢胞性病変を指摘され、そのサイズは徐々に増大を認めた。移植腎部を中心とする腹痛を度々訴えるようになり、嚢胞穿刺排液およびminocycline注入療法を2回施行したが、嚢胞液が再貯留するとともに腹痛が増悪・持続するため、当院にて腹腔鏡下移植腎嚢胞開窓術を施行した。摘出した嚢胞壁の免疫染色では、リンパ管のマーカーであるD2-40が陽性であった。経過から、移植後に行ったプロトコール生検により移植腎内のリンパ管を損傷・閉塞したために発生したリンパ嚢胞と診断された。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J01175&link_issn=&doc_id=20140806420010&doc_link_id=130005093153&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F130005093153&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：腎移植・血管外科研究会  

【目的】献腎提供の少ない日本では、長い待機期間を有しないとレシピエントとして選定されることが少ない。そのため高齢者、長期透析患者が選定される事が非常に多い。そこで、このようなマージナルなレシピエントに若年者の提供腎がどのような影響をうけるのか、また高齢者の提供腎が、若年者のレシピエントの予後にどのような影響をうけるのか検討した。【対象と方法】われわれの施設における献腎移植55症例に対してドナー・レシピエントを50歳未満・50歳以上でそれぞれ分類し、その予後を検討した。【結果】10年生着率はG1 84.2%、G2 54.4%、G3 83.3%、G4 53.8%で若年者のレシピエントにおいて若年者ドナー(G1)に比べ高齢者ドナー(G2)では有意に生着率は低かった(P=0.014)。しかし高齢者レシピエントではドナー年齢で生着率に有意差を認めなかった(G3:G4 P=0.409)。【結語】若年者のレシピエントに高齢者の提供腎を移植する事は、その予後を不良とする可能性が高い。余命の長い若年者のレシピエントに対しては、年齢による振り分け選定を検討する必要性がある。(著者抄録)

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：(株)日本医学館  

献腎提供の少ないわが国では、長い待機期間を有しないと献腎移植のレシピエントとして選択されることが少ない。2002年1月にレピエント選択基準が変更となってから、さらに高齢者、長期透析患者が選択されることが多い。しかし、このようなマージナルなレシピエントに若年からの提供腎がどのような影響を受けるのか、また高齢者からの提供腎が若年のレシピエントの予後にどのような影響を受けるのか検討された報告はない。そこで、新潟大学、日本臓器移植ネットワーク東日本支部における献腎移植のドナー・レシピエントを50歳未満と50歳以上でそれぞれ分類し、その予後を検討した。(著者抄録)

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Language：Japanese   Publisher：新潟医学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J00990&link_issn=&doc_id=20140603160014&doc_link_id=%2Fdg3nigta%2F2014%2Fs12802%2F010%2F0094-0095%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdg3nigta%2F2014%2Fs12802%2F010%2F0094-0095%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(株)日本メディカルセンター  

腎移植は免疫抑制薬の進歩などにより成績が向上しており,優れた腎代替療法として有用性が確立している.糖尿病性腎症(DM腎症)の慢性腎不全患者は,心血管疾患(CVD)による死亡リスクが高く,透析導入後の予後は非常に悪い.一方,腎移植では透析に比べて生命予後の改善が望める.さらに透析による合併症を避けて腎移植を行うことが,移植腎生着率・生存率の上昇につながる.DM腎症患者ではとくにCVDを含む合併症の評価が重要であり,術前に十分な精査を行う.術後は手術侵襲,免疫抑制薬などにより糖尿病が悪化することが多く,厳密な血糖コントロールが必要となる.またDM腎症の再発が腎生着率を低下させるため,移植後も長期にわたり糖尿病の治療が必要である.(著者抄録)

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J-GLOBAL

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Language：Japanese   Publisher：(一社)日本泌尿器内視鏡学会  

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Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：(一社)日本泌尿器内視鏡学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY-BLACKWELL  

DOI： 10.1111/xen.12060_19

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY-BLACKWELL  

Web of Science

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(株)日本メディカルセンター  

新規透析導入患者の高齢化を迎えるわが国では,高齢者に対する腎移植について真剣に考えなければならない.当科でも,高齢者に対する腎移植の割合は年々増加しており,生着率(death censored graft survival)は,若年レシピエントと比較しても有意差はなかった.しかし,高齢者レシピエントは移植腎が生着したまま,他の要因で死亡する症例(death with functioning graft)が多かった.高齢者からの腎提供も安全に行われており,夫婦間の移植も増加している.高齢者に対する腎移植レシピエントもしくは,ドナーに関する適応,成績を含め文献を加えて考察した.(著者抄録)

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(株)日本医学館  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2013&ichushi_jid=J01126&link_issn=&doc_id=20130327320004&doc_link_id=10031164081&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F10031164081&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

Language：Japanese   Publisher：(株)日本医学館  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：日本小児腎不全学会  

症例1(総排泄腔遺残症を合併した11歳女児)。今回、小児ドナーからの献腎移植目的で入院となった。頻回の腹部手術による癒着と複雑な血管形成と総排泄腔遺残のために尿路再建などを必要としたため、腎移植手術時間は7時間25分と通常の腎移植の2倍の時間を要した。移植腎は1次腎移植の母親の提供腎に比べると小さく、レシピエントの体格には丁度よい大きさであった。尚、移植後はタクロリムス、ミコフェノール酸モフェチル、メチルプレドニゾロンほか、バシリキシマブによる免疫抑制療法を導入することで、拒絶反応や感染症もなく、良好な経過が得られた。症例2(総排泄遺残症を合併した10歳女児)。今回、父親をドナーとする生体腎移植目的で入院となった。症例1に比べ腹部手術歴が少な癒着も少なかったこと、ドナー腎も成人男性にしてはやや小さめだったことなどから腎移植手術時間は4時間20分であった。尚、移植後は症例1と同様に免疫抑制療法が導入されたが、移植後5日目にプログラフ脳症が疑われたためネオーラルに変更した。その結果、経過は良好であった。

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Language：Japanese   Publisher：腎移植・血管外科研究会  

ABO血液型不適合腎移植では、抗血液型抗体によって抗体関連型拒絶反応(AMR:antibody mediated rejection)を引き起こす可能性があるため、抗血液型抗体価が高い症例は、いままでは移植困難とされてきた。今回我々は、抗血液型抗体価が高い症例に対し脱感作療法、抗体除去療法を行うことでAMRを発症することなく経過良好な血液型不適合腎移植を3症例経験したので報告する。(著者抄録)

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Language：Japanese   Publisher：(一社)日本臓器保存生物医学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2011&ichushi_jid=J03926&link_issn=&doc_id=20111122150009&doc_link_id=10.11378%2Forganbio.18.207&url=https%3A%2F%2Fdoi.org%2F10.11378%2Forganbio.18.207&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY-BLACKWELL  

Web of Science

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Language：Japanese   Publisher：日本小児腎不全学会  

33歳女性。12歳時に巣状分節性糸球体硬化症(FSGS)と診断され、ステロイド、シクロスポリン、ヘパリン、血漿交換(PEX)にて加療されていた。だが、急速に腎不全が進行し、15歳時に血液透析導入となった。今回、母親をドナーとして血液型一致生体腎移植が施行されたものの、移植後の翌日に高度の蛋白尿、尿量低下が認められた。精査の結果、移植後FSGS再発と診断され、PEXやLDL吸着、リツキシマブ投与を行ったところ、尿蛋白は減少した。目下、移植後1年の時点で尿蛋白0.2g/日、Cr0.98g/dlと良好に経過している。

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Language：Japanese   Publisher：(一社)日本臓器保存生物医学会  

ドナー由来のABO血液型抗原を合成する糖転位酵素の測定について検討した。2006年4月〜2008年7月迄のABO不適合腎移植20例、ABO適合腎移植5例を対象に、血清中・移植腎生検試料中に存在するドナー血液型転移酵素活性を検討した。全てのポイントでドナー血液型転移酵素活性を測定できたが、一定の傾向はなく、不適合例と適合例で大きな違いはなかった。

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Language：Japanese   Publisher：(一社)日本臓器保存生物医学会  

新潟大学医歯学総合病院薬剤部では、腎移植患者に対して服薬指導や薬力学的な薬効評価のための免疫抑制薬の感受性試験を実施している。また、テーラーメード医療進展のために、新たな免疫能の評価法であるImmuKnowの実施も検討している。腎移植後の免疫抑制療法は、複数からなる免疫抑制薬から構成されており、移植時期によって投与量も変化することから、腎移植患者に対する服薬指導は移植に対して専門的な知識を持つ薬剤師が担当すべきである。

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Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：(NPO)日本法医学会  

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Language：Japanese   Publisher：(NPO)日本呼吸器外科学会  

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Language：Japanese   Publisher：(株)日本医学館  

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Language：Japanese   Publisher：(株)日本医学館  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2011&ichushi_jid=J01175&link_issn=&doc_id=20110328480369&doc_link_id=10.5980%2Fjpnjurol.102.343_5&url=https%3A%2F%2Fdoi.org%2F10.5980%2Fjpnjurol.102.343_5&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：(株)日本医学館  

33歳女。12歳の時に巣状分節性糸球体硬化症(FSGS)と診断され、透析歴18年を経てABO血液型一致生体腎移植を行った。術前に2回の血漿交換療法(PE)を行ったが術後2日目に無尿となり、急性拒絶反応を疑いステロイドパルス療法を施行した。連日のPEを行うも無尿が術後6日まで続いたため、リツキシマブを投与した。移植腎生検の電子顕微鏡所見で早期のFSGS再発と診断された。術後9回のPE、リツキシマブ投与およびアルブミンの連日投与により、18日目より利尿を得て20日目に透析離脱となった。PEをLDL吸着療法に切り替え移植腎機能は安定したが、術後50日目頃より尿蛋白量が増加したため、アンギオテンシン受容体拮抗薬を投与したが尿蛋白はさらに増加した。リンパ球表面マーカ(CD19、20、21)の軽度上昇で、68日目にリツキシマブを再投与したところ、CD19は速やかに低下し、尿蛋白量は減少している。

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Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本臓器保存生物医学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(株)日本医学館  

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Language：Japanese   Publisher：新潟医学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2010&ichushi_jid=J00990&link_issn=&doc_id=20101228030013&doc_link_id=%2Fdg3nigta%2F2010%2F012408%2F013%2F0475-0475%26dl%3D2&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdg3nigta%2F2010%2F012408%2F013%2F0475-0475%26dl%3D2&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_5.gif

Language：Japanese   Publisher：日本小児腎不全学会  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(株)日本医学館  

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Language：Japanese   Publisher：(NPO)日本呼吸器外科学会  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2010&ichushi_jid=J01175&link_issn=&doc_id=20100323480651&doc_link_id=10.5980%2Fjpnjurol.101.326_4&url=https%3A%2F%2Fdoi.org%2F10.5980%2Fjpnjurol.101.326_4&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：(一社)日本泌尿器科学会  

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Language：Japanese   Publisher：(株)医薬ジャーナル社  

臓器移植で用いられる免疫抑制薬において、CD25やCD20を標的とするバシリキシマブやリツキシマブなどがわが国でも使用されるようになり、移植臓器の生着率が向上しただけでなく、より困難な移植も可能になってきている。さらに最近、特定の分子やシグナルを標的とした免疫抑制薬の開発が進み、bortezomibが治療困難であった抗体関連型の拒絶反応に、また、anti-thymocyte gulobulinがステロイド抵抗性の拒絶反応などに効果があると考えられている。その他、細胞周期を調節するeverolimusや副刺激を阻害するbelataseptなど、近い将来、臓器移植の分野で活躍する免疫抑制薬を中心に解説したい。(著者抄録)

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Language：Japanese   Publisher：医薬ジャ-ナル社  

CiNii Article

CiNii Books

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Language：Japanese   Publisher：腎移植・血管外科研究会  

移植腎の管理をするためには、移植腎生検は簡便で安全な検査であるが、時として腎出血、腎血腫など重大な合併症を発症する恐れがある。今回我々は、移植腎生検後腎血腫を併発し、それによって急性腎不全におちいった2症例を経験した。移植腎生検によって発症した血腫は、その容量が小さくても腎被膜下や筋膜内において、移植腎を圧迫し腎血流が低下すると急性腎不全を併発してしまう。出血が増大してこない場合は保存的に経過をみて血腫が吸収されるのをまったほうがよい場合と、早期に止血、血腫除去術をするほうがよい場合とある。判断に難渋した場合、どのようにして治療方針を立てるべきか、文献的考察をまじえて報告する。(著者抄録)

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Language：Japanese   Publisher：(株)メジカルビュー社  

腎機能障害患者の術後管理では、術前の補正が非常に重要である。術後の腎不全で最も多いのは腎前性腎機能障害であり、その防御のための術後管理においては、水分・電解質管理、栄養の補給が必要である。使用薬剤、透析に関しても注意が必要であり、造影剤は必要最小限の量にとどめ、また、鎮痛に関しては非ステロイド性消炎鎮痛剤使用は避け術後の硬膜外麻酔にて管理する。利尿薬、抗菌薬等においてもその特性を理解し、腎機能に合わせて使用すべきである。

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Language：Japanese   Publisher：(株)日本医学館  

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Language：Japanese   Publisher：(株)日本医学館  

ABO血液型不適合移植が盛んに行われるようになったいま、再度ABO血液型糖鎖抗原について見直すことは重要であると考える。そもそも糖鎖抗原は多様性に富み、構成する単糖の配列や種類、分岐などによりその種類は幾通りにもなる。ABO血液型糖鎖抗原の糖鎖構造も5種類あるとされ、過去にType 4の糖脂質であるglobo属が特徴的であると報告された。しかし、Type 4はA型の集合管にしか発現しておらず、移植免疫を考えた場合、血管内皮細胞に発現するABO血液型糖鎖抗原の構造や分布を考えなければならないが、いまだ報告はない。筆者らは、ABO血液型糖鎖抗原を持つプロテオーム解析で、いくつかの特徴的な蛋白質が腎臓の血管内皮細胞でABO血液型糖鎖抗原を持つことを報告した。それらを踏まえて、過去のデータとともに腎臓とABO血液型糖鎖抗原について考えたい。(著者抄録)

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Language：Japanese   Publisher：(株)日本医学館  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(株)日本医学館  

ABO血液型不適合腎移植においては、抗A抗B抗体による抗体関連型急性拒絶反応による移植腎喪失を防ぐことが最大の課題であり悲願であった。近年、B細胞表面に発現する機能分子であるCD20に対するヒトマウスキメラ型モノクローナル抗体であるリツキシマブを脱感作療法に用いることにより、多くの症例で脾摘を行うことなく安全に抗体関連型急性拒絶反応を回避し、"免疫学的順応"を誘導することが可能となった。(著者抄録)

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Language：Japanese   Publisher：(一社)日本泌尿器科学会  

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J-GLOBAL

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Language：Japanese   Publisher：(株)メディカルレビュー社  

[1]一般的に腎移植患者は血栓症を引き起こしやすい状態(hypercoagulable state)にある。[2]腎移植後血栓症は、様々な因子が複雑に絡み合い発症すると考えられ、統一した予防法は未だ確立していない。[3]移植腎に発生する血栓症においては大きくグラフト側の因子、レシピエント側の因子に分けられる。[4]抗凝固療法により血栓症の発生を抑制できたとする報告もあるが、出血などの合併症も同時に報告されている。[5]EBMに基づいた予防法の確立が望まれる。(著者抄録)

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(株)東京医学社  

腎移植にかかわる腎臓の画像診断について中心的役割を果たすのは、術前のCT(computed tomography)と術後の超音波検査である。術前のドナーの腎血管に関する情報は、安全な手術を行ううえで非常に重要であり、従来行われていた侵襲的な血管造影法に代わってCT angiography(CTA)やmagnetic resonance angiography(MRA)が普及してきた。術後検査で重要なのは、拒絶反応や合併症の有無を迅速に判断することであり、簡便かつリアルタイムに情報を得られる超音波検査はいまだ中心的役割を果たす。腎移植に関して大きな問題となる拒絶反応や感染症以外に、腎移植後に起こりうる合併症として腎血管性高血圧、悪性腫瘍、尿路合併症などが重要である。(著者抄録)

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：(株)東京医学社  

ABO血液不適合腎移植術を行った13例を対象に、術前にミコフェノール酸モフェチル(MMF)/低用量ステロイドによる脱感作療法と抗CDモノクローナル抗体(リツキシマブ)の併用と脾摘を行わない移植術について検討した。その結果、全例生存し、生着を12例に認め、血清クレアチニン値も良好で、抗体関連型拒絶反応は見られなかった。細胞性拒絶反応は6例に見られたが全例軽快し、合併症も、アデノウイルス出血性膀胱炎、肺うっ血、溶血症、十二指腸潰瘍、移植後糖尿病が見られたが改善した。生着を認めなかった1例は、腎機能は順調であったが、感染のコントロールのため移植腎摘除術を施行した。又、白血球減少症によりMMFの中止とG-CSF投与を行った症例も散見された。

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：English   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会  

尿路に発生する子宮内膜症は稀である.今回,我々は両側に発生した尿管子宮内膜症を経験したので報告する.症例は46歳,女性,顔面浮腫を主訴に来院した.初診時,BUNは52.0mg/dl,Creは4.83mg/dlと腎不全を認めCTにて両側水腎症を指摘され当科初診となった.逆行性腎盂造影では両側尿管下部の閉塞を伴った水腎症を認め,MRIにて左卵巣嚢腫を認めた.CA125は93U/mlと上昇しており試験開腹にて子宮内膜症による尿管狭窄と判断した.Gn-RHアナログによるホルモン治療と尿管拡張術,尿管カテーテル留置を繰り返すが水腎症は改善されず,一側合流尿管-尿管端側吻合・尿管膀胱新吻合術(psoas hitch)が施行された.術後,両側水腎症と腎機能は改善した.症例はextrinsic type尿管子宮内膜症と考えられた(著者抄録)

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：新潟医学会  

59歳男.S状結腸穿孔による汎発性腹膜炎で緊急手術を行った.その後ショック,呼吸困難などを繰り返し,人工呼吸管理,カテコラミン投与から離脱困難となった.高カルシウム血症,見当識障害なども見られ,ACTH低値,cortisol低値から続発性副腎不全と診断し,hydrocortisoneの内服を開始したところ,速やかに全身状態が改善した.後に長期にわたり皮膚掻痒症に対し,Celestamineが投与されていたことが判明した.Celestamineは一錠中betamethasone 0.25mgを含んでおり,そのために続発性副腎不全をきたしたと考えられた.問診と薬歴聴取の重要性を再認識するとともに,続発性副腎不全には特異的な症状がなく,同様の症状が消化器外科手術後にも見られることから,見過ごされている可能性があり注意が必要であると考えられた

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会  

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Language：Japanese   Publisher：(株)日本医学館  

52歳女.妊娠中毒症の後に慢性腎不全となり34歳で血液透析を導入した.血液型一致,HLA1MMの伯母をドナーとする生体腎移植を希望し,陳旧性肺結核再燃予防目的の3剤併用療法を6ヵ月施行した.全経過を通じて白血球減少症が認められたことが,アスペルギルス,ノカルジア感染症のrisk factorとなっていた.組織適合性が良好であること,感染症予防の為に免疫抑制療法は代謝拮抗薬を外していたにも拘わらずアスペルギルス感染症が発症し,治療の過程でノカルジア感染症も認められた.感染症のrisk factorが存在する場合は胸部CT等による厳重な管理が必要である

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Language：Japanese   Publisher：(一社)日本泌尿器科学会  

57歳男.間欠的右側腹部痛と肉眼的血尿を主訴に受診した.腹部X線で尿管結石と診断し,内服薬を処方しかたが改善しなかった.高尿酸血症の存在よりX線透過性の尿酸結石として診断し,入院となった.腹部膨満が出現し緊急腹部X線で右側腹部にガス像,緊急腹部CTで後腹膜脂肪組織に同様にガス像を認めガス壊疽を疑い,右側腹部腹壁切開による緊急ドレナージを施行した.術後ショック状態となり,ICUに緊急入院となった.抗生剤はクリンダマイシン,イミペネム,塩酸バンコマイシンなどを使用した.無尿状態であったためCHDFを開始し,併せてエンドトキシン吸着を施行した.膿培養でガス壊疽と診断した.高圧酸素療法を試みたが全身状態は改善しなかった.入院後3日目よりDICを併発し急速に病変は拡大したため開腹手術が不可能となり,感染源が特定できないまま,死亡した.剖検の結果,回盲部に多数の細かい憩室があり,その一つが後腹膜に穿孔していたことが判明した

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：新潟医学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会  

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