岩見 大基

Donors with resolved hepatitis B virus (HBV) infection may be a solution for the organ shortage for kidney transplantation (KT). The purpose of this study was to clarify the current state of HBV markers after KT from donors with resolved HBV infection to HBV naïve recipients and the rate of HBV reactivation in recipients with resolved HBV infection. Furthermore, we investigated HBV covalently closed circular DNA (cccDNA) in transplanted organs from donors with resolved HBV infection and the capability of HBV replication in kidney cell lines. We retrospectively analysed the HBV status of 340 consecutive donors and recipients who underwent KT in a single centre. We prospectively measured cccDNA by real-time polymerase chain reaction in kidney biopsy specimens of 32 donors with resolved HBV infection. HBV reactivation was found in three recipients with resolved HBV infection (4.8%, 3/63) after KT. We analysed 45 cases of transplantation from donors with resolved HBV infection to HBV-naive recipients. One case (2.2%, 1/45) became seropositive for hepatitis B core antibody (anti-HBc) and in another case (2.2%, 1/45), HBV-DNA was detected qualitatively in an HBV naive recipient with a donor with resolved HBV infection. In the latter case, cccDNA was measured in the donor kidney during KT. HBV replication was observed in kidney cell lines with HBV plasmid transfection. In conclusion, the risk of reactivation in anti-HBc-positive donors is relatively low. However, post-transplant HBV monitoring should be conducted in all at-risk cases.

Introduction: We present a case of urothelial carcinoma in a renal allograft successfully treated with pembrolizumab. Case presentation: A 39-year-old woman presented with nausea and anorexia 9 years after a renal transplantation. Positron emission tomography revealed a neoplasm of the renal pelvis of the allograft and multiple lymph nodes with peritoneal metastasis. A diagnosis of a non-muscle-invasive bladder tumor with peritoneal dissemination and jejunal metastasis of urothelial carcinoma was made. After five cycles of gemcitabine and carboplatin, the tumor progressed and pembrolizumab was administered. One week after the first dose, the allograft was rejected, necessitating arterial embolization. After the second cycle, the patient developed Stevens-Johnson syndrome. After discontinuing pembrolizumab, positron emission tomography revealed no increased tumor activity. A complete response was achieved for 21 months without additional treatment. Conclusion: Pembrolizumab was effective in treating urothelial carcinoma of the renal allograft; however, allograft rejection and loss should be considered.

症例は54歳女性,原疾患不明の慢性腎不全に対して献腎移植を施行され腎機能は安定していた.移植後6年で膀胱刺激症状を契機に膀胱右側の筋層浸潤性膀胱癌が判明し肺転移も伴っていた.StageIV膀胱癌として免疫抑制剤を減量しゲムシタビン・シスプラチン療法を開始したところ,4コース後に転移巣が消失した.新規病変を認めなかったため開放手術にて右腎尿管膀胱全摘術および回腸導管造設を行った.摘出標本で左尿管断端に上皮内癌病変を認めたため,2ヵ月後に残存した左固有腎尿管に対して鏡視下で腎尿管全摘術を施行したが,悪性所見は認めなかった.Surgical CRとして無治療経過観察としたが,術後半年で多発肺転移が出現した.ゲムシタビン・カルボプラチン療法を導入し,4コース終了までは肺転移がやや縮小したが,5コース終了後は増悪を認めていた.追加治療を希望せず緩和治療へ移行となり膀胱全摘後1年9ヵ月で癌死した.腎移植後であっても膀胱全摘および尿路変向手術は可能で,免疫抑制剤の調整により化学療法も完遂できた.腎移植後の進行性膀胱癌にエビデンスのある治療方針はなく,腎機能障害を有し免疫抑制状態であることを認識し,個々の症例で適切な薬物治療や外科的治療の選択をする必要がある.(著者抄録)

Background: A positive flow-cytometry T cell crossmatch (FTXM) has important prognostic implications, even when the complement-dependent cytotoxicity crossmatch is negative. Recent studies have shown that ABO incompatibility is associated with positive FTXM, but the underlying mechanism remains poorly understood. Cases: In five ABO blood type O recipients of kidneys from wives with type B, FTXM was positive but complement-dependent cytotoxicity crossmatch was negative. Application of a solid-phase technique (LABScreen) revealed no case with antibodies to donor-specific human leukocyte antigen. After removal of type B antibodies from patient sera, FTXM was negative for all five patients. In one tested case, the eluate prepared from the donor's T lymphocyte agglutinated only type B red blood cells, implying the existence of blood type B substances on donor T lymphocytes. Discussion: False-positive FTXM reflects blood type B substrates bound to T lymphocytes. Repeat FTXM after incubation with donor-type red blood cells (to adsorb anti-ABO antibodies) was negative. This phenomenon explains the discrepancy between FTXM and solid-phase bead assays. Demonstration of type B substances on donor T lymphocytes is necessary before absolute test validity is confirmed. Conclusion: False-positive FTXM may be associated with type B antibodies bound to T lymphocytes when a blood type O recipient receives tissue from a type B donor. This phenomenon explains the false-positive FTXM observed in the setting of ABO-incompatible kidney transplantation.

Surgical training using live animals such as pigs is one of the best ways of achieving skilled techniques and fostering confidence in preclinical medical students and surgeon trainees. However, due to animal welfare ethics, laboratory animals' usage for training should be kept to a minimum. We have developed a novel kidney organ model utilizing a simple procedure in which the kidney is first refluxed with N-vinyl-2-pyrrolidone (NVP) solution for 1 hour in its bath, followed by permeation for 23 hours, with a subsequent freshwater refluxed for 48 hours in the washing step. Surgical simulation of the prepared kidney model (NVP-fixed kidney) was compared with three types of other basic known simulation models (fresh kidney, freeze-thaw kidney, and FA-fixed kidney) by various evaluations. We found the NVP-fixed kidney to mimicked fresh kidney function the most, pertaining to the hardness, and strength of the renal parenchyma. Moreover, the NVP-fixed kidney demonstrated successful blood-like fluids perfusion and electrocautery. Further, we confirmed that surgical training could be performed under conditions closer to actual clinical practice. Our findings suggest that our model does not only contribute to improving surgical skills but also inspires the utilization of otherwise, discarded inedible livestock organs as models for surgical training.

Background: Removal of anti-blood group antibodies is important for successful ABO-incompatible kidney transplantation (ABOi-KTx). Double-filtration plasmapheresis (DFPP) using albumin solution removes antibodies effectively. However, fibrinogen is largely removed resulting in hemostatic failure. Herein, we designed an altered combination of plasma membranes in DFPP (novel DFPP, nDFPP) to retain more fibrinogen while removing IgG, and assessed its efficacy and safety compared with conventional DFPP (cDFPP). Methods: Consecutive ABOi-KTx recipients (from 2015 to 2018) were enrolled. For the first membrane, we used Cascadeflo EC-50W in nDFPP and Plasmaflo OP-08W in cDFPP, and Cascadeflo EC-20W as the second membrane in both modalities. Removal rates (RR) of IgG, IgM and fibrinogen per DFPP session, and adverse events were compared with historical control patients who underwent cDFPP before ABOi-KTx, between 2006 and 2015. Results: nDFPP and cDFPP groups included 12 and 23 cases, respectively. nDFPP was inferior to cDFPP in RR of IgG and IgM. nDFPP was also inferior to cDFPP in the decline in anti-blood group IgG and IgM antibody titers. However, fibrinogen was more preserved in nDFPP compared with cDFPP, indicating that nDFPP has more selective removal properties (median RR of IgG, IgM, and fibrinogen: 62.1%, 15.7% and 37.6%, respectively, in nDFPP; and 74.5%, 85.0% and 76.6%, respectively, in cDFPP). In the comparison of hemostatic function among the patients who had arteriovenous fistula for hemodialysis, prolonged hemostasis (> 20 min) at the cannulation site was significantly less frequently observed in nDFPP group (1 in 9 cases, 9.1%) than in cDFPP group (all 18 cases, 10%, p < 0.0001). Conclusions: nDFPP preserves fibrinogen while removing anti-blood type IgG antibodies before ABOi-KTx.

<title>Abstract</title><sec> <title>Background</title> Simultaneous pancreas and kidney transplantation (SPK) is a treatment option for patients with end-stage renal disease due to type 1 diabetes mellitus. We report a patient with a refractory fistula due to leakage from the duodenal stump of the pancreas graft after an SPK with bladder drainage who was successfully treated with a percutaneous direct injection of <italic>N</italic>-butyl-2-cyanoacrylate (NBCA). </sec><sec> <title>Case presentation</title> A 60-year-old female with a 33-year history of type 1 diabetes mellitus and a 10-year history of renal replacement therapy underwent an SPK in 2015. At the time of transplantation, an abdominal aortic aneurysm with a high risk of rupture was treated by a Y-graft replacement prior to the SPK. Bladder drainage of the pancreas graft was chosen to avoid a vessel graft infection. The patient’s postoperative course was uneventful. The patient was discharged on postoperative day 93 with good-functioning pancreas and kidney grafts. One and a half years after the operation, the patient was found to have acute graft pancreatitis and a leak from the duodenal stump of the pancreas graft due to a paralytic neurogenic bladder. The insertion of an indwelling catheter into the bladder and the endoscopic-guided insertion of a catheter into the graft pancreatic duct through the duodenum/bladder anastomosis did not result in the closure of the fistula. Therefore, NBCA was injected at the site of the leak point using CT-guided technique. The fistula was completely closed immediately after the injection, with no recurrences of leaks. </sec><sec> <title>Conclusions</title> A percutaneous direct injection of NBCA is one of the treatment options to treat intractable fistulas. </sec>

Herein we report the case of a 37-year-old woman with recurrence of lupus nephritis (LN) in a renal allograft during pregnancy. She had developed end-stage renal disease due to LN and was put on hemodialysis at the age of 26 years. She underwent kidney transplantation at the age 28 years. Maintenance immunosuppressants included methylprednisolone, tacrolimus, and mycophenolate mofetil, which were changed to azathioprine when she desired pregnancy. The renal allograft function remained stable and seemingly disease-free until proteinuria and functional decline occurred during the pregnancy (age: 34 years). The baby was delivered by performing a cesarean section at 33 weeks of gestation. Renal allograft biopsy revealed crescent formation. Light microscopy revealed tuft necrosis and endocapillary proliferation. Immunofluorescence microscopy revealed the deposition of immunoglobulin G and C1q. A recurrence of LN (ISN/RPS class IV-G [A/C]) was diagnosed, and the patient was treated with pulse steroid therapy and azathioprine was replaced with mycophenolate mofetil. This treatment improved acute or active lesions of LN and temporarily benefited the renal allograft function. Unfortunately, there were irreversible chronic changes and a gradual decline in the renal allograft function.

OBJECTIVES: To evaluate the relationship between the creatinine reduction ratio between postoperative days 1 and 2 and post-transplantation clinical outcomes after living donor kidney transplantation. METHODS: Clinical data of patients who underwent living donor kidney transplantation at Jichi Medical University Hospital, Tochigi, Japan, between 2006 and 2019 were retrieved. The creatinine reduction ratio between postoperative days 1 and 2 was calculated based on the formula: (Cre1 - Cre2) × 100/Cre1; patients were then classified into either the slow graft function (creatinine reduction ratio between postoperative days 1 and 2 ≤30%) or immediate graft function (creatinine reduction ratio between postoperative days 1 and 2 >30%) group. We carried out the log-rank test and multivariate Cox proportional hazards regression analyses to assess graft survival and rejection-free survival, and the unpaired t-test and multivariate linear regression to assess post-transplantation estimated glomerular filtration rates. Multivariate analyses used age, sex, dialysis duration, ABO compatibility, donor-specific antibody positivity and medically complex living donors as explanatory variables. RESULTS: Of the 272 patients, 30 and 242 were in the slow graft function and immediate graft function groups, respectively. Multivariate Cox proportional hazards regression analyses showed a significantly higher incidence of overall and death-censored graft loss in the slow graft function group than the immediate graft function group. The frequency of rejection after 1 week post-transplantation did not differ within the groups. Post-transplantation estimated glomerular filtration rates tended to decline earlier in the slow graft function group than in the immediate graft function group; however, the difference was not statistically significant. CONCLUSIONS: The creatinine reduction ratio between postoperative days 1 and 2 could potentially predict long-term outcomes after living donor kidney transplantation. Using the creatinine reduction ratio between postoperative days 1 and 2 and other conventional indicators might allow accurate risk classification and appropriate therapeutic interventions.

Introduction: After kidney transplantation, patients should be treated with caution and monitored for surgical complications. Among the possible surgical complications, strangulation ileus after kidney transplantation is rare. Case presentation: A 59-year-old woman who had undergone kidney transplantation at 41 years of age presented to our hospital with lower abdominal pain. She was diagnosed with strangulation ileus and underwent emergency surgery. In the lower right abdomen, the small intestine was compressed by cord-like tissue running from the intraperitoneal space to the retroperitoneal space. We confirmed that the cord-like tissue was the ureter of the transplanted kidney. The necrotic small intestine was resected, and ureter-ureteral anastomosis of the ureter of the transplanted kidney was performed. Conclusion: All surgical procedures, including ureteroneocystostomy, require careful attention. The occurrence of some postoperative surgical complications can be prevented by carefully performing the kidney transplantation procedure.

Anemia and vitamin D deficiency are associated with allograft failure, and hence, are potential therapeutic targets among kidney transplant recipients (KTRs). We conducted a multicenter, two-by-two factorial, open-label, randomized clinical trial to examine the effects of anemia correction and vitamin D supplementation on 2-year change in eGFR among KTRs (CANDLE-KIT). We enrolled 153 patients with anemia and >1-year history of transplantation across 23 facilities in Japan, and randomly assigned them to either a high or low hemoglobin target (>12.5 vs. <10.5 g/dl) and to either cholecalciferol 1000 IU/day or control. This trial was terminated early based on the planned interim intention-to-treat analyses (α = 0.034). Among 125 patients who completed the study, 2-year decline in eGFR was smaller in the high vs. low hemoglobin group (i.e., -1.6 ± 4.5 vs. -4.0 ± 6.9 ml/min/1.73 m2 ; P = 0.021), but did not differ between the cholecalciferol and control groups. These findings were supported by the fully adjusted mixed effects model evaluating the rate of eGFR decline among all 153 participants. There were no significant between-group differences in all-cause death or the renal composite outcome in either arm. In conclusion, aggressive anemia correction showed a potential to preserve allograft kidney function.

PURPOSE: Although transplanting two kidneys from a single donor to two recipients has some advantages, the right and left kidneys are not anatomically identical; thus, a surgical procedure considering the anatomical features of the donor kidneys is needed when transplanting them into the opposite renal fossae. Based on vast experience, the surgical details of pig orthotopic kidney transplantation from one donor to two recipients was reported. METHODS: When the right kidney was transplanted to the left renal fossa, the graft was inverted upside down, not backwards, thus ensuring that the anteroposterior relationship of the renal vessels was maintained and anatomically natural vascular anastomosis could be performed. RESULTS: Using this technique, we could have developed a pig experimental model that is safe and has a high success rate, even for researchers in the middle of their training. This technique of inverting the graft upside down was reported in human kidney transplantation to make vascular anastomosis easier. CONCLUSIONS: In pig orthotopic kidney transplantation from one donor to two recipients, an anatomically natural vascular anastomosis could be performed via inverted grafting when the right kidney was transplanted into the left renal fossa.

Introduction: Femoral nerve palsy is a rare but serious complication of kidney transplantation. We report a case of femoral nerve palsy following kidney transplantation and conduct a review of the literature on this complication. Case presentation: A 35-year-old woman with end-stage kidney disease, underwent kidney transplantation in the right iliac fossa. The day after the transplantation, she could not straighten her right leg. Physical examination revealed a paresis of her right quadriceps muscle. The patient's sensation of her right thigh was also impaired. We diagnosed her with femoral nerve palsy caused by inappropriate compression from a self-retaining retractor. Rehabilitation was started immediately. The patient's motor weakness gradually improved, and the patient became able to walk independently 4 weeks later. However, the patient's neuropathic pain sustained 6 months after her kidney transplantation. Conclusion: The improper use of self-retaining retractors can lead to femoral nerve palsy in patients undergoing kidney transplantation.

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

【研究目的】小児献腎移植の臨床経過につき検討する。【対象】北海道大学病院にて小児献腎移植を行った6例(男4、女2)。【結果】年齢は中央値13.4歳(6.2〜17.1)、待機期間は中央値0.9年(0.2〜12)、ドナーは心停止1例、脳死5例であった。3例が2次移植であり、術前透析は血液透析1例、腹膜透析4例、未透析1例であった。1例は下大静脈閉塞による静脈灌流不全で術当日に移植腎摘出となった。他の5例の総阻血時間は中央値494分(356〜616)で、全例術後透析を要さなかった。術後中央値23日(16〜73)で退院し、退院時のクレアチニンは中央値0.5mg/dL(0.4〜2.1)であった。現在術後中央値32ヵ月(10〜100)が経過し、4例は経過良好であるが、1例は術後25ヵ月目に服薬不全にて移植腎機能喪失となった。【結論】小児献腎移植は待機期間が短く、小児腎不全患者の治療法として考慮すべきである。(著者抄録)

症例は18歳、男性。ネフロン癆による腎不全に対し、11歳時に母をドナーとする血液型不一致生体腎移植を施行した。移植1年目、2年目の定期生検で異常所見は認めなかったが、3年目の定期生検で傍尿細管毛細血管(PTC)炎と糸球体炎を認め、PTCにC4dの沈着を認めた。また、HLA Class I、IIのde novoドナー特異的抗体(DSA)が検出されたが、血清クレアチニンの上昇はなくsubclinical antibody-mediated rejection(AMR)と診断した。タクロリムスとミコフェノール酸モフェチルの増量、ステロイドパルス治療、リツキシマブの投与を行った。4年目生検では病理所見の改善とDSAの陰転化を認めた。現在移植後6年11ヵ月経過し、腎機能に悪化はなくDSAの陰転化を維持している。Subclinical AMRに対する治療介入は有効である可能性があり早期診断が重要である。(著者抄録)

【研究目的】移植腎障害(KGI)を非侵襲的に診断しうるバイオマーカーの探索を尿中のエクソソーム・微小嚢胞(EV)中のmRNA解析により行った。【方法】全国11施設にて計127症例の腎移植後の尿検体を集めた。各尿検体からEV RNAを抽出し定量RT-PCR測定を行い、腎生検を含む病理診断結果と比較しマーカー候補遺伝子ならびに複数候補による診断式の診断性能を検証した。【結果】拒絶反応の鑑別では以前に報告したANXA1の上昇は確認できなかったものの、CXCL9、CXCL10、UMODがT細胞性拒絶反応(TCMR)で上昇し、慢性抗体関連拒絶反応(cABMR)ではSPNS2の上昇が確認された。Sparse Logistic Regression(SLR)解析による複数マーカー候補からなる診断式にてcABMRと他のKGI群とAUC 0.875で鑑別できることを確認した。また、臨床上判定が困難な慢性カルシニューリン毒性に比しても、SLR解析でAUC 0.886でcABMRの鑑別が可能であった。加えて、間質線維化・尿細管萎縮や慢性腎障害重症度と相関がみられるマーカー候補POTEMを確認し、SLR解析による診断式でおのおのAUC 0.830、0.850で鑑別できた。【結論】尿中EV RNA解析によりKGIを非侵襲的に診断できうる可能性を示した。(著者抄録)

【研究目的】先天性下部尿路通過障害に起因する慢性腎不全(ESKD)に対する腎移植の成績を検討する。【方法】先天性下部尿路通過障害に起因するESKDにより腎移植を行った男児4症例を対象とし術前後の下部尿路機能および排尿管理と移植腎機能について検討した。【結果】移植時年齢は平均7.4歳であった。閉塞解除後の腎移植前に施行した尿流動態検査では1例で低コンプライアンス膀胱を認め膀胱拡大術を施行され、その後自己導尿管理とした。また、1例では排尿筋過活動を認め抗コリン薬が開始された。他の2例は検査上異常を認めなかったが1例は尿失禁を認め抗コリン薬が開始された。術後の尿路感染症は1例のみで、抗コリン薬を中止した術後13年目に発症し抗コリン薬が再開となった。現在移植後平均14.1年が経過し、拒絶反応の発症はなく、平均のeGFRは48.4mL/minと移植腎機能は良好である。【結論】先天性下部尿路通過障害を有する患者に対する腎移植は、下部尿路機能を評価し適切に管理することにより良好な成績が得られる。(著者抄録)

症例は16歳、男性。出生時にVATER連合と診断され、腎機能障害も認めたため保存期腎不全管理が開始となった。7歳時に腎移植の相談のため当科初診されたが、生体腎移植は両親が糖尿病であり適応外であった。その後、緩徐に腎機能障害が進行し腎代替療法導入が必要な状況となったが、腹膜透析、血液透析は社会背景から困難であり、先行的献腎登録を行った。献腎登録から1年後の16歳時に、脳死ドナーの第一候補に選定され先行的献腎移植を施行した。現在術後1年7ヵ月経過し、腎機能は良好に経過している。本邦において献腎ドナーの数に飛躍的な増加はないが、レシピエント選定基準の変更に伴って小児腎不全患者に優先的に献腎移植できる環境が整いつつある。さらに、先行的献腎移植登録が可能となったため当症例のような先行的献腎移植が可能な状況になった。小児腎不全患者において生体ドナー候補がいない場合には先行的献腎移植登録を考慮すべきである。(著者抄録)

＜文献概要＞先天性腎尿路異常(CAKUT)は腎尿路における先天異常の総称で,腎,腎盂尿管,膀胱,尿道の多様な疾患を含んでおり,小児の末期腎不全(ESKD)の原因として,もっとも頻度の高い疾患である.低形成腎や異形成腎では小児期にESKDに至る場合が多いが,尿路奇形においては繰り返す尿路感染症(UTI)などにより腎機能障害が進行し,成人になってからESKDに至る場合も多い.そのため,小児期の管理のみならず,成人に達してからの腎臓内科への慢性腎臓病管理の適切な移行と,泌尿器科による長期的な尿路管理によるUTIの予防,腎代替療法の管理が重要である.

【研究目的】腎移植における、慢性抗体関連型拒絶反応(CAAMR)に対する治療の長期成績について検討する。【方法】CAAMRに至った腎移植時15歳以下の4例の治療内容、治療成績について検討した。【結果】診断時期は中央値で移植後5.5年(4.5〜12.4年)であった。全例プロトコール生検で診断された。2症例はステロイドパルス、血漿交換、グスペリムス、リツキシマブ、IVIg投与の多剤併用+抗体除去療法を行った。腎機能は徐々に悪化傾向で、病理学的にCAAMRの進行を認めるが、治療後8年目の現在も生着中である。2症例はリツキシマブ投与のみを行った。1例は治療後4年目も腎機能は安定しており病理学的にも改善を認めたが、もう1例は治療後3年目に移植腎喪失に陥った。【結論】多剤併用+抗体除去療法を行ったCAAMR症例は、長期生着していることより有効な治療である可能性がある。リツキシマブ投与も有効例を認めるが、今後適応症例の検討が必要である。(著者抄録)

41歳の女性。二分脊椎による神経因性膀胱で自己導尿を行っていた。27歳時に血液透析導入、40歳時に献腎移植を受け透析を離脱した。移植後1年経過し右前腕内シャントを局所麻酔下に結紮閉鎖した。しかし術後もシャント血流が残存し、超音波検査にて結紮部の末梢側に多発するAVFが確認された。右前腕AVF設置の3年前に橈骨骨嚢腫の摘出を受けており、その術後に橈骨遠位部に後天性AVFを形成したと考えられた。血管造影にて橈骨遠位部の多発AVFは塞栓困難と考えられたため内シャント閉鎖術後9ヵ月目に全身麻酔にて残存AVFの結紮切除を行い、AVFは消失した。特発性AVF既往は認めず、医原性の術後AVFと判断した。(著者抄録)

【背景・目的】先天性ネフローゼ症候群(CNS)は腎移植を行わなければ長期生存は困難であるが、腎移植前の全身管理にも苦慮する。当院では、CNS症例の術前の管理として片側固有腎摘および内科的腎摘を施行し、腹膜透析(PD)を施行し、その後に腎移植を施行する方針としている。今回、当院で施行したCNS患児4症例の腎移植後の成績について検討した。【対象】2000年から2013年までに当科で施行したCNSに対する腎移植4例(年齢:1.8〜2.8歳)を対象とした。【結果】移植前の固有腎摘出は3例に施行し、3例とも同時にPDカテーテルを留置した。残り1例は左腎萎縮があり、PDカテーテル留置のみ行った。PDで成長を待ち、体重17.7±6.5kgで腎移植を行った。全例同時に移植側の固有腎摘を行った。4例中1例で血栓性微小血管障害を発症し移植後25日目に移植腎摘出し、現在血液透析にて管理中である。他3例中1例では移植腎静脈血栓のため腎機能発現せず、2ヵ月後に二次移植を行い、その後7.8年生着している。残り2例はそれぞれ4.3年、14.3年移植腎は生着しており、安定して経過している。【結語】CNS症例では固有腎摘や透析など、段階的に治療を行い、全身状態を整えた状態で腎移植を施行することが重要である。(著者抄録)

献腎移植のPrimary non-function(PNF)による移植成績低下を改善するために、北海道では2004年にブタを使用した摘出トレーニングを導入した。このトレーニング導入後の2004年1月から2014年2月までの期間中に北海道で摘出が行われた献腎ドナーは66例(脳死ドナー17例、心停止49例)であった。ドナー年齢は中央値52歳(21-76)、男性35例、女性31例、ドナー搬入時Crは中央値0.9(0.36-1.40)mg/dLで、温阻血時間は中央値2(0-29)分であった。摘出前に無尿となった症例は11例認め、無尿時間は中央値で10(3-19)時間であった。我々は原則として無尿時間が24時間を超えた場合や腎摘出後のベンチでの灌流が不良な場合は、移植適応外と判断している。摘出された132腎のうち、4腎が適応外(萎縮腎1、灌流不良3)で128腎が移植可能であった。また、11腎が膵腎同時移植として道内外の外科系施設へ提供され、117腎が道内施設で移植された。PNFを1例に認めたが、トレーニング導入前に比べPNF症例は減少した。また、摘出時間も有意に短縮された。PNF1例は二次移植小児例でのレシピエントの静脈血栓によるPNFであり、ドナー条件や摘出手術とは無関係であった。当院ではこの117例中38例(32.5%)が移植された。うち11例(脳死6例、心停止5例)において0hr生検と1hr生検を採取し、後日永久標本で移植腎を評価した。病理上、4例で急性尿細管障害を認めたが、尿細管上皮障害の有無や程度にかかわらず11例中10例で術後透析を要しており、ベースライン生検で移植後の経過は予測できなかった。ドナー死戦期のバイタル変動や、温阻血時間、総阻血時間、摘出術自体による腎実質障害など様々な要因が重なるため、迅速のHE染色標本のみで移植の可否を決定することは不可能と思われた。北海道における初期(1980〜2001年)の献腎移植経過と比較し、摘出技術の向上と、無尿時間と灌流状態による腎提供可否判断により、最近の献腎移植成績は良好であった。(著者抄録)

ObjectivesTo evaluate the risk for urological complications after kidney transplantation at a single medical center in Japan. MethodsIn the present study, 408 kidney recipients (255 men, 153 women) were enrolled. There were 349 living and 59 deceased donors. The average age of the recipients was 42.513.5years, and the average pretransplant dialysis period was 71.888.2months. Ureteroneocystostomy was carried out on 347 patients, and ureteroureterostomy on 61 patients. We investigated the relationship between pretransplant duration of dialysis and bladder capacity, and examined the risk factors for urological complication. We also evaluated the incidence of vesicoureteral reflux in 191 recipients who underwent ureteroneocystostomy during transplantation. ResultsThe preoperative duration of dialysis therapy showed a significant negative correlation with bladder capacity (R-2=0.33, P&lt;0.001). The overall urological complication rate was 3.4% (14 patients), including urinary leakage (12 patients) and ureteral stricture (two patients). Univariate analysis showed that atrophic bladder, long-term dialysis therapy, deceased donor and ureteroureterostomy were associated with a higher incidence of urological complications (odds ratio 8.05, 4.43, 3.42 and 3.35; P&lt;0.01, P=0.01, P=0.04 and P=0.04, respectively). Furthermore, multivariate analysis showed that atrophic bladder was the only significant factor associated with urological complications (odds ratio 10.37; P=0.01). Among 191 recipients, vesicoureteral reflux was observed in 32 (16.8%). The incidence of vesicoureteral reflux was significantly higher in patients with atrophic bladder. ConclusionsBladder atrophy in renal transplant recipients after long-term dialysis therapy is associated with a higher risk of urological complications.

AimsTo investigate changes in glucose tolerance, insulin secretion and insulin sensitivity in Japanese recipients before and 1 year after renal transplantation. MethodsWe conducted a study of Japanese recipients without diabetes who underwent renal transplantation at Hokkaido University Hospital. A 75-g oral glucose tolerance test was performed before and 1 year after renal transplantation in these recipients. Insulin sensitivity was estimated using the Matsuda index and homeostasis model assessment of insulin resistance (HOMA-IR). Insulin secretion was evaluated based on the insulin secretion sensitivity index-2 (ISSI-2). ResultsOf the 62 renal transplant recipients, 31 were diagnosed as having impaired glucose tolerance before transplantation. Among these 31 recipients, after 1 year, four had developed new-onset diabetes after transplantation, and nine had impaired glucose tolerance. Unexpectedly, 18 changed from impaired to normal glucose tolerance. When these recipients with impaired glucose tolerance were classified into a non-amelioration group and an amelioration group, the ISSI-2 was significantly reduced, with no significant changes in the Matsuda index or HOMA-IR, in the non-amelioration group 1 year after renal transplantation. By contrast, ISSI-2 and Matsuda index values were significantly increased, with no significant changes in HOMA-IR values in the amelioration group. ConclusionsMore than half of Japanese renal transplant recipients with impaired glucose tolerance had normal glucose tolerance 1 year after renal transplantation. These results suggest that an increase in insulin secretion and whole insulin sensitivity was associated with improvement in glucose tolerance in these recipients.

腎移植後の内シャントの閉鎖の時期・適応についてはっきりした基準はないが閉鎖理由はシャントの瘤化、疼痛、心負荷過剰、スティール症候群などがある。臨床的に心負荷過剰が明らかでなくても内シャント閉鎖後3-6ヵ月で血行動態が改善する。自然閉塞については当科および諸家の検討は同様の傾向で、30-40%の症例で閉塞し、4年以降では自然閉塞しなかった。以上を踏まえ当科では移植後1年の定期移植腎生検で明らかな異常を認めないことを確認し、自然閉塞の可能性も説明したうえで内シャント閉鎖を勧め、各自の判断で決めてもらっている。数年経過をみて自然閉塞の兆候がない場合に外科的閉鎖という選択肢もあると思われる。(著者抄録)

Background. De novo donor-specific antibody (dnDSA), especially against class II HLA, correlates with chronic active antibody-mediated rejection (CAAMR), which eventually leads to graft loss. It would be helpful if we could identify the patients at high risk of dnDSA development in terms of histocompatibility. Structure-based matching strategy assessing mismatched epitopes/eplets by comparing polymorphic amino acid sequences can predict the risk of development of dnDSA and CAAMR. However, it has not been evaluated in Japanese patients whose diversity in HLA is limited. Patients and Methods. We retrospectively studied 55 living related kidney transplant patients and ascertained donor and recipient HLA-A,-B,-DRB1, and-DQB1. The number of mismatched eplets was determined using an algorithm, HLAMatchmaker version 3. The relationship between characteristics of mismatched eplets and development of CAAMR was evaluated. Results. There were 8 patients in the CAAMR group and 47 in the control group. The numbers of mismatched HLAs (3.6 +/- 1.2 in CAAMR and 3.7 +/- 2.0 in control groups), mismatched eplets (32.2 +/- 10.4 in CAAMR and 34.4 +/- 19.8 in control groups), mismatched DRB1 eplets (11.2 +/- 4.3 in CAAMR and 11.5 +/- 7.9 in control groups), and mismatched DQB1 eplets (9.2 +/- 4.3 in CAAMR and 10.5 +/- 7.3 in control groups) were not significantly different. Significantly more patients had at least one highly immunogenic mismatched eplet (62.5% in CAAMR and 25.5% in control groups; P = .024 by chi(2) test). Conclusions. The presence of highly immunogenic mismatched eplets is associated with development of CAAMR.