岩見 大基

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<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<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.

Background. We investigated whether the age of donor kidneys influences the incidence of nocturnal polyuria in patients with successful renal transplantation (RTX). Methods. Eighty-five patients (45 men and 40 women) undergoing RTX (median age, 47 years) were included in this study. Twenty-four-hour bladder diaries were kept for 3 days, and nocturnal polyuria was defined as a nocturnal polyuria index (nocturnal urine volume/24-hour urine volume) of >0.33. Risk factors for nocturnal polyuria were analyzed in patients with RTX by means of the Mann-Whitney U test, chi(2) test, and a logistic regression analysis. Results. End-stage renal disease (ESRD) developed from diabetes mellitus in 16 patients (19%). Sixty-five patients (76%) received pre-transplant dialysis, with a median duration of 5 years. The median serum creatinine level and body mass index at the most recent visit were 1.2 mg/dL and 21.2 kg/m(2), respectively. On the basis of the 24-hour bladder diaries, nocturnal polyuria was identified in 48 patients (56%). A logistic regression analysis revealed that diabetes mellitus as the original disease for ESRD was the only risk factor for nocturnal polyuria (odds ratio, 8.95; 95% confidence interval, 2.01-65.3; P = .0028). The age of donor kidneys at examination did not affect the incidence of nocturnal polyuria (P = .9402). Conclusions. Nocturnal polyuria was not uncommon in patients with successful RTX. Diabetes mellitus as the original disease for ESRD was the only risk factor for nocturnal polyuria, whereas the age of donor kidneys at examination did not affect the incidence of nocturnal polyuria. Thus, nocturnal polyuria is caused by recipient factors but not donor factors.

【背景、目的】下部尿路異常を伴う腎不全患者に対する腎移植においては尿路治療、透析療法と腎移植の時期、タイミングに苦慮することがある。【対象と方法】2001〜2013年に腎移植を施行した下部尿路異常を伴う閉塞性・逆流性腎症による慢性腎不全11症例(男性6、女性5例)を対象とし、尿路単独異常4例と、尿路以外の先天性疾患も合併していた7症例(多発異常群)に分け、先天性尿路異常やその他の異常に対する治療、透析療法の導入時期、腎移植との関係について検討した。【結果】尿路単独群は全例小児で、腎移植までに尿路異常が整復されており先行的腎移植が4例中3例で可能であった。排尿管理についても自排尿が可能であり成人として適正な膀胱容量が得られていた。一方、多発異常群では尿路以外の先天異常の治療過程で腎機能の悪化が進行し透析導入を余儀なくされる症例が7例中4例あり、尿路の完全な整復を待たずに移植を先行し、腎移植後に尿路手術を追加した症例を3例認めた。また2例は腎移植が20歳を超えてから施行されていた。尿路管理は1例を除き間欠的導尿などの継続した泌尿器科的対応が必要であった。【結語】多発異常群であっても尿路の低圧ドレナージが獲得された段階で腎移植を行い良好な腎機能を維持することができているが、先天異常の治療、尿路の整復、透析導入、腎移植のタイミングを症例毎に適切に判断することが必要である。(著者抄録)

Cytomegalovirus (CMV) infection is themost common infectious complication following solid organ transplantation. Ganciclovir (GCV)-resistant CMV infection may be fatal, and is difficult to treat while avoiding allograft rejection. A 31-year-old woman received a second ABO-incompatible kidney transplant, from her father. Induction therapy consisted of basiliximab and rituximab followed by maintenance immunosuppression with tacrolimus, mycophenolate mofetil, and methylprednisolone. Her CMV serostatus was D+/R- at second transplant and she received prophylactic low-dose valganciclovir (VGCV). BK polyoma virus nephropathy (BKVN) developed 7 months after transplant concurrent with CMV hepatitis and retinitis. VGCV was increased to a therapeutic dose combined with reduced immunosuppression with minimal methylprednisolone (2mg/day) and everolimus (0.5mg/day). However, pp65 antigenaemia continued to increase for 6 weeks. Her CMV was defined as ganciclovir (GCV)-resistant. Foscarnet was therefore administered and her CMV disease resolved within 2 weeks. Kidney allograft dysfunction developed 9 months after transplant, and graft biopsy showed tubulointerstitial injury with crystal deposition suggesting foscarnet nephrotoxicity, with no findings of BKVN or rejection. Kidney function recovered after cessation of foscarnet and the patient had good graft function 18 months after transplant. This case demonstrates the successful use of foscarnet to treat GCV-resistant CMV infection after ABO-incompatible kidney transplant complicated with BKVN, without acute allograft rejection. This case further highlights the need to establish appropriate management for CMV D+/R- patients to avoid the acquisition of GCV-resistant gene mutations.

Regulatory T cells (Tregs) are essential to suppress unwanted immunity or inflammation. After islet allo-transplant Tregs must migrate from blood to allograft, then via afferent lymphatics to draining LN to protect allografts. Here we show that Tregs but not non-Treg T cells use lymphotoxin (LT) during migration from allograft to draining LN, and that LT deficiency or blockade prevents normal migration and allograft protection. Treg LT alpha beta rapidly modulates cytoskeletal and membrane structure of lymphatic endothelial cells; dependent on VCAM-1 and non-canonical NF kappa B signalling via LT beta R. These results demonstrate a form of T-cell migration used only by Treg in tissues that serves an important role in their suppressive function and is a unique therapeutic focus for modulating suppression.

症例は27歳、男性で、原疾患はIgA腎症。58歳の父をドナーにB型からA型への血液型不適合腎移植の予定となった。アレルギー反応のためリツキシマブは投与できず、脾臓摘出を併用し、腎移植を行った。免疫抑制剤はタクロリムスを含む4剤を使用した。移植後の経過は良好で術後17日目にHb11.1g/dlで退院となった。術後27日目の定期受診時にHb7.4g/dlと貧血を認めた。抗A抗体価を測定したところ、IgMが2倍と陽性でありpassenger lymphocyteによる溶血性貧血と診断した。タクロリムスの減量、O型赤血球の輸血にて貧血は改善し、以後再発を認めず、移植腎機能も安定している。(著者抄録)

T-bet is essential for natural regulatory T cells (nTreg) to regulate Th1 inflammation, but whether T-bet controls other Treg functions after entering the inflammatory site is unknown. In an islet allograft model, T-bet(-/-) nTreg, but not induced Treg, failed to prolong graft survival as effectively as wild-type Treg. T-bet(-/-) nTreg had no functional deficiency in vitro but failed to home from the graft to draining lymph nodes (dLN) as efficiently as wild type. T-bet regulated expression of adhesion-and migration-related molecules, influencing nTreg distribution in tissues, so that T-bet(-/-) nTreg remained in the grafts rather than migrating to lymphatics and dLN. In contrast, both wild-type and T-bet(-/-) CD4(+) conventional T cells and induced Treg migrated normally toward afferent lymphatics. T-bet(-/-) nTreg displayed instability in the graft, failing to suppress Ag-specific CD4(+) T cells and prevent their infiltration into the graft and dLN. Thus, T-bet regulates nTreg migration into afferent lymphatics and dLN and consequently their suppressive stability in vivo.

B cells are known to control CD4T cell differentiation in secondary lymphoid tissues. We hypothesized that IL-10 expression by marginal zone precursor (MZP) regulatory B cells controls the differentiation and positioning of effector and regulatory T cells during tolerization. Costimulatory blockade with donor specific transfusion (DST) and anti-CD4OL mAb in C57BL/6 mice induced tolerance to allogeneic cardiac allograft. B cell depletion or IL-10 deficiency in B cells prevented tolerance, resulting in decreased follicular regulatory CD4(+) T cells (Tfr) and increased IL-21 expression by T follicular helper (Tfh) cells in the B cell and T cell zones. IL-21 acted with IL-6 to induce CCR6(+) Th17 that caused rejection. Deficiency or blockade of IL-6, IL-21, IL-21R, or CCR6 prevented B cell depletion-induced acute cellular rejection; while agonistic mCCL20-Ig induced rejection. Adoptive transfer of IL-10(+/+) MZP in tolerogen treated CD19-Cre(+/-):IL-10(fl/fl) mice rescued the localization of Tfh and Tfr cells in the B cell follicle and prevented allograft rejection. MZP B cell IL-10 is necessary for tolerance and controls the differentiation and position of Th17, Tfh and Tfr cells in secondary lymphoid tissues. This has implications for understanding tolerance induction and how B cell depletion may prevent tolerance. (C) 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Background: We investigated risk factors for lower urinary tract (LUT) dysfunction and LUT symptoms in patients who successfully underwent renal transplantation (RTX). Material/Methods: Ninety-five patients (54 males and 41 females) undergoing RTX (median age: 45 years old) at Hokkaido University Hospital were included in this study. Uroflowmetry (UFM), postvoid residual urine volume (PVR), and 24-h bladder diaries were performed. We analyzed risk factors for voiding dysfunction, urinary frequency, polyuria, nocturia, and nocturnal polyuria after RTX using logistic regression analysis. Results: End-stage renal disease arose from diabetes mellitus in 18 patients (19%). Pre-transplant dialysis had been carried out in 74 patients. Voiding dysfunction as assessed by UFM and PVR was observed in 24 patients (27%). Based on the 24-h bladder diaries, we identified frequent micturition in 29 patients (35%), polyuria in 44 (54%), nocturia in 30 (37%), and nocturnal polyuria in 46 (56%). A multivariable logistic regression analysis revealed that diabetes mellitus, which may cause autonomic disorders, was a risk factor for voiding dysfunction and nocturnal polyuria. A risk factor for frequent micturition and nocturia was older age at RTX. Being female was a risk factor for polyuria, which suggested that fluid intake in relation to body weight was higher in females. Conclusions: LUT dysfunction and LUT symptoms were not uncommon in patients who successfully underwent RTX. LUT dysfunction and LUT symptoms need to be considered in patients with risk factors such as diabetes mellitus, older age at RTX, and being female, even after successful RTX.

Background. Blocking CD40-CD40L costimulatory signals induces transplantation tolerance. Although B-cell depletion prevents alloantibody formation, nonhumoral functions of B cells in tolerance have not been well characterized. We investigated whether specific subsets of B cell or B cell-derived interleukin (IL)-10 contribute to tolerance. Methods. Wild type C57BL/6, or B cell-specific interleukin (IL)-10(-/-) (CD19-Cre(+/-)::IL-10(fl/fl)) mice, received vascularized BALB/c cardiac allografts. BALB/c donor-specific splenocyte transfusion and anti-CD40L monoclonal antibody were used as tolerogen. B cells were depleted with antimouse CD20 monoclonal antibody. Various B-cell subsets were purified and characterized by flow cytometry, reverse transcription polymerase chain reaction, and adoptive transfer. Results. B-cell depletion prevented costimulatory blockade-induced allogeneic tolerance. Costimulatory blockade increased IL-10 in marginal zone precursor (MZP) B cells, but not other subsets. In particular, costimulatory blockade did not change other previously defined regulatory B-cell subsets (Breg), including CD5(+)CD1d(hi) Breg or expression of TIM1 or TIM4 on these Breg or other Breg cell subsets. Costimulatory blockade also induced IL-21R expression in MZP B cells, and IL-21R(+) MZP B cells expressed even more IL-10. B-cell depletion or IL-10 deficiency in B cells prevented tolerance in a cardiac allograft model, resulting in rapid acute cardiac allograft rejection. Adoptive transfer of wild type MZP B cells but not other subsets to B cell-specific IL-10 deficient mice prevented graft rejection. Conclusions. CD40 costimulatory blockade induces MZP B cell IL-10 which is necessary for tolerance. These observations have implications for understanding tolerance induction and how B cell depletion may prevent tolerance.

15歳男児。出生時に先天性ネフローゼ症候群で腹膜透析導入後、2歳時に生体腎移植を施行した。術後25日目、感染を契機に急激な移植腎血栓をきたし移植腎摘出術、下大静脈血栓除去術を施行。術後血液透析を導入し献腎待機を継続した。非アルコール性脂肪性肝炎に伴う肝線維化、汎血球減少を認め11歳時に脾臓摘出した。今回、抗ドナー抗体(Class II)陽性の脳死ドナーに適合し、血漿交換、リツキシマブ投与による脱感作後、脳死腎移植を施行した。下大静脈閉塞のため下肢血流は側副血行路が拡張しており、移植腎静脈を奇静脈、下腸間膜静脈に順次吻合を行ったが、いずれも静脈圧上昇による移植腎鬱血をきたした。下腸間膜静脈の近位部に再吻合して閉創したが、鬱血した腎から腹腔内に3L近くの出血を認め、移植腎を摘出し血液透析を維持している。今後の腎移植の可能性について静脈鬱血の対策と再評価を行い、下肢の静脈血の側副血行路のドレナージがより低圧に期待できる外腸骨静脈遠位側に移植すべく再度の献腎移植登録を予定している。(著者抄録)

Background. Trafficking and differentiation of naive CD4+ and regulatory Tcells (Treg) within the lymph node (LN) are integral for tolerance induction. The LN is comprised of stromal fibers that dictate lymphocyte migration and LN structure, organization, and microanatomic domains. Distribution of the stromal fiber ER-TR7 changes within the LN after antigenic challenge, but the contributions of ER-TR7 to the resulting immune response remain undefined. We hypothesized that these stromal fiber structural changes affect T cell fate and subsequently allograft survival. Methods. C57BL/6 mice were left naive (untreated) or made immune or tolerant (donor-specific BALB/c splenocyte transfusion -/+ anti-CD40L monoclonal antibody), or made tolerant and received anti-ER-TR7 monoclonal antibody. Donor-specific T-cell migration was visualized by adoptive transfer of carboxyfluorescein diacetate, succinimidyl ester-labeled TEa T cell receptor transgenic CD4+ cells. Immunohistochemistry was performed on LNs to detect stromal fiber distribution, structure, CCL21 presence, and Treg and donor-specific cell location relative to high endothelial venules (HEV). Naive, tolerant, and tolerant + anti-ER-TR7 mice received BALB/c heterotopic cardiac allografts and graft survival was monitored. Results. The ER-TR7 distribution changed after the induction of tolerance vs. immunity. Treating tolerant mice with anti-ER-TR7 altered HEV basement membrane structure and the distribution of CCL21 within the LN. These differences were mirrored by changes in the migration of naive and Treg cells within and surrounding the HEV. AntiER- TR7 prevented tolerance induction and resulted in allograft inflammation and rejection. Conclusions. These results identify ER-TR7 as an important component of LN structure in tolerance and a direct target for immune modulation.

Background. Circulation of leukocytes via blood, tissue and lymph is integral to adaptive immunity. Afferent lymphatics form CCL21 gradients to guide dendritic cells and T cells to lymphatics and then to draining lymph nodes (dLN). Vascular endothelial growth factor C and vascular endothelial growth factor receptor 3 (VEGFR-3) are the major lymphatic growth factor and receptor. We hypothesized these molecules also regulate chemokine gradients and lymphatic migration. Methods. CD4(+) T cells were injected into the foot pad or ear pinnae, and migration to afferent lymphatics and dLN quantified by flow cytometry or whole mount immunohistochemistry. Vascular endothelial growth factor receptor 3 or its signaling or downstream actions were modified with blocking monoclonal antibodies (mAbs) or other reagents. Results. Anti-VEGFR-3 prevented migration of CD4+ Tcells into lymphatic lumen and significantly decreased the number that migrated to dLN. Anti-VEGFR-3 abolished CCL21 gradients around lymphatics, although CCL21 production was not inhibited. Heparan sulfate (HS), critical to establish CCL21 gradients, was down-regulated around lymphatics by anti-VEGFR-3 and this was dependent on heparanase-mediated degradation. Moreover, a Phosphoinositide 3-kinase (PI3K)alpha inhibitor disrupted HS and CCL21 gradients, whereas a PI3K activator prevented the effects of anti-VEGFR-3. During contact hypersensitivity, VEGFR-3, CCL21, and HS expression were all attenuated, and anti-heparanase or PI3K activator reversed these effects. Conclusions. Vascular endothelial growth factor C/VEGFR-3 signaling through PI3K alpha regulates the activity of heparanase, which modifies HS and CCL21 gradients around lymphatics. The functional and physical linkages of these molecules regulate lymphatic migration from tissues to dLN. These represent new therapeutic targets to influence immunity and inflammation.

Lymph nodes (LNs) are integral sites for the generation of immune tolerance, migration of CD4(+) T cells, and induction of Tregs. Despite the importance of LNs in regulation of inflammatory responses, the LN-specific factors that regulate T cell migration and the precise LN structural domains in which differentiation occurs remain undefined. Using intravital and fluorescent microscopy, we found that alloreactive T cells traffic distinctly into the tolerant LN and colocalize in exclusive regions with alloantigen-presenting cells, a process required for Treg induction. Extracellular matrix proteins, including those of the laminin family, formed regions within the LN that were permissive for colocalization of alloantigen-presenting cells, alloreactive T cells, and Tregs. We identified unique expression patterns of laminin proteins in high endothelial venule basement membranes and the cortical ridge that correlated with alloantigen-specific immunity or immune tolerance. The ratio of laminin alpha 4 to laminin alpha 5 was greater in domains within tolerant LNs, compared with immune LNs, and blocking laminin alpha 4 function or inducing laminin alpha 5 overexpression disrupted T cell and DC localization and transmigration through tolerant LNs. Furthermore, reducing alpha 4 laminin circumvented tolerance induction and induced cardiac allograft inflammation and rejection in murine models. This work identifies laminins as potential targets for immune modulation.

10歳以下で体重が25kg以下の小児腎移植患者4例(女児、1.4〜8.2歳)を対象に、タクロリムス徐放製剤(TACER)の1日2回投与法による血中濃度の安定化について検討した。腎移植後の免疫抑制法はバシリキシマブで導入し、ミコフェノール酸モフェチルとメチルプレドニゾロンを併用した。症例1では腎移植後4年9ヵ月後にタクロリムス(TAC)の2回投与法からTACERへ変更し、1回投与を継続したが服薬不全から急性拒絶反応(AR)をきたし、その治療とTAC濃度維持のためTACERの1日2回投与法へ変更した。症例2では総排泄腔遺残症に伴う腸管ストマ、尿路ストマの状態で腎移植後、TACERの1日1回投与法で維持していたが、移植創部の細菌感染症後にARをきたし、TACERを1日2回投与法として1日量も増量した。症例3は献腎移植後4日目にTACの持続静脈内投与法から内服へ移行する際にTACER1日2回投与法へ直接移行した。症例4では移植後TACの2回投与法を維持していたが、ピークとトラフの濃度差が顕著なため、移植後24日目にTACERの1日2回投与法へ移行した。

Calcineurin inhibitors (CNIs) have considerably improved renal allograft survival. However, their chronic use has various adverse effects, including hypertension, hyperlipidemia, and nephrotoxicity. We conducted a retrospective study of kidney transplant recipients using a CNI withdrawal protocol. Eleven of 13 patients who had stable graft function on triple-drug therapy including a cyclosporine (CsA) were enrolled in this study. The dose of CsA was reduced by 20% every two wks until complete withdrawal. The mean period between the baseline and last biopsies was 97 (range: 21-123) months. No patient had an acute rejection episode during follow-up. Progression of interstitial fibrosis and tubular atrophy was seen in five and six cases, respectively. Arteriolar hyalinosis improved in three cases, but worsened in four. No patient lost his graft during the study. The mean serum creatinine level was 1.30 +/- 0.26 mg/dL at baseline and stable for 10 yr after elimination (1.26 +/- 0.11 mg/dL). At the end of the study, four of the eleven patients had reduced their antihypertensive drugs, and one patient had stopped hyperlipidemia treatment. CNI withdrawal can be implemented safely in stable renal transplant recipients and might lead to improved patient outcomes. Additional specific evidence of CNI nephrotoxicity should be elucidated.

Purpose of reviewThe mechanisms of tolerance induction and maintenance remain incompletely understood and have yet to be translated to clinical practice. Advances in imaging techniques have allowed precise examination of cell interactions in the lymph node, often in real time. Herein we review evidence that lymph node structure is dynamic and controls the character of the immune response in a multistep, multiplayer dance. T-cell responses in particular can be initiated or influenced in regions beyond the canonical T-cell zone. We propose that the cortical ridge is one such region required for induction and maintenance of tolerance.Recent findingsLymph node domains are more complex than T-cell and B-cell zones. Different domains are important for different types of immune responses. These domains are in part defined by dynamic, malleable physical structures that guide cell interactions and influence immune outcomes.SummaryFurther probing as to how lymph node stromal cells and fibers interact with and determine the character of immune responses should yield fundamental insights into tolerance and immunity. Manipulation of lymph node structure and associated unique cell types and molecules may allow therapeutic interventions in the tolerogenic process.

14歳男児、骨折を契機に高血圧を指摘され、造影CTで腹腔動脈起始部から両側腎動脈起始部に至る大動脈狭窄を指摘された。大動脈狭窄部から腹腔動脈、上腸間膜動脈、両側腎動脈が分枝して全て狭小化していた。左後腹膜的に胸腹部大動脈置換、右腎動脈と腹腔動脈に8mm径の人工血管を介在させ再建、左腎動脈を大動脈グラフトに端側吻合した。術後18日目に高血圧と腎機能悪化を認め、血管造影で左腎動脈吻合部の屈曲と判明した。術後4週目に左腎を摘出し右腸骨窩へ自家腎移植した。2年後の現在、血圧・腎機能は安定している。左腎動脈と置換した大動脈グラフトは近接しており、閉創時の左腎の変位が吻合部屈曲の原因となったと考えられた。(著者抄録)

Background. Spontaneous rupture risk of a renal artery aneurysm (RAA) is extremely low. Indications for surgical repair of RAA remain uncertain. Objective. Long-term outcomes of conservative therapy and surgical repair were evaluated. Patients. The study included 58 patients (17 males, 41 females) who were diagnosed with RAA during the last 21 years. Median age at the time of diagnosis was 62 (19-85) years, and the median follow-up 69 months (range 3-216). Methods. The patients were divided into two groups, conservative group (n = 30) who had been followed with blood pressure control, and treatment group (n = 29), who underwent an intervention. Results. Multiple efferent aneurysmal branches were observed in seven conservative and 16 treatment cases (P = .002). The median maximum diameter of the aneurysm was lower in the conservative than the treatment group (15 versus 25 mm, P = .005). Two conservative group cases showed increases in aneurysm size during follow-up. The hypertensive state showed essentially no change in either group during the follow-up. Renal function decreased with age similarly both in conservative and treatment groups. Conclusions. Our conservative management criteria for RAA are justifiable and even too strict.

Background: Conditions associated with high intraglomerular filtration pressure can cause secondary focal segmental glomerulosclerosis (FSGS). Unilateral renal artery stenosis (RAS) or its occlusion results in FSGS-like changes and the nephrotic syndrome in the contralateral kidney due to hyperfiltration. However, it has been rarely reported that stenosis of a renal arterial branch can result in FSGS-like changes in a different portion in the same kidney allograft. Case presentation: A 60-year-old male kidney recipient developed allograft dysfunction after angiotensin II receptor blockade for hypertension 4 months after transplantation. It was proven that one of two arterial branches of the graft was markedly stenotic. Graft dysfunction improved after percutaneous transluminal arterioplasty (PTA), however; the stenosis recurred and massive proteinuria developed 5 months later. Graft biopsy showed ischemic changes in the region fed by the stenotic artery branch and in contrast FSGS-like changes in the region fed by the other branch. His clinicopathological manifestation including massive proteinuria almost normalized after the repeat PTA. Conclusion: Here we report a case of secondary FSGS of a kidney allograft due to severe RAS of a branch of the same kidney, in which clinical and pathological improvement were confirmed after radiological intervention. When moderate to severe proteinuria appear, secondarily developed FSGS as well as primary (recurrent or de novo) FSGS should be taken into account in kidney transplant recipients.

BACKGROUNDS: The deep inferior epigastric artery (DIEA), which feeds the lower rectus abdominis muscle (lower RAM), is usually transected in kidney transplantation. In this study, we investigated whether preservation of DIEA can prevent lower RAM atrophy. METHODS: Two hundred and forty-five kidney transplant recipients (150 men and 95 women) were enrolled in the study (mean age 39.9 years) and were divided into two groups according to whether DIEA was transected (group A, n = 175) or preserved (group B, n = 70). The extent of lower RAM atrophy calculated in computed tomography (performed 1 year after transplantation) and incidence of lower RAM atrophy were compared between the two groups. The most predictive factors for lower RAM atrophy were assessed using a multivariate logistic regression model. RESULTS: The extent of lower RAM atrophy was significantly lower in group B (15.0 ± 18.5%) than that in group A (38.9 ± 25.4%, P = 0.003). The incidence of lower RAM atrophy was less prevalent in group B (20.0%) compared with that in group A (62.9%, P < 0.001). The sacrifice of DIEA was the only independent predictive factor for lower RAM atrophy (P < 0.001). CONCLUSIONS: Preservation of DIEA during kidney transplant can prevent lower RAM atrophy.

Background. Successful kidney transplantation (KT) can theoretically reconstitute body composition of a patient with chronic kidney disease (CKD). However, the practical changes have not been well documented. We evaluated changes in body composition among candidates before and 1 year after KT. Methods. We enrolled 37 male and 18 female kidney recipients eligible for comparison of their body mass index (BMI), body composition, and lipid metabolism before and 1 year after KT. Twenty-one patients had been induced with a calcineurin inhibitor, mycophenolate mofetil, steroid, and basiliximab, and 34 others underwent steroid withdrawal on postoperative day 3. The body composition was analyzed using bioelectrical impedance. We also analyzed changes in BMI and lipid profiles. Results. There was no significant change in BMI (21.4 +/- 3.1 vs 21.7 +/- 3.5 kg/m(2)). Regarding body composition, the water level decreased significantly (61.2 +/- 4.9% vs 58.3 +/- 5.3%; P &lt; .05). In contrast, fat significantly increased (16.4 +/- 6.7% vs 20.3 +/- 7.1%; P &lt; .05). More interestingly, successful KT significantly decreased the muscle and bone mass at 1 year after KT (37.3 +/- 5.1% vs 34.8 +/- 4.7%; 16.3 +/- 2.1% vs 15.2 +/- 2.1%; respectively; P &lt; .05). Serum lipid profiles of total cholesterol, low-density lipoprotein cholesterol, and triglyceride worsened after KT. Comparing the 2 protocols, there was no difference in any item. Conclusions. Care must be taken even after successful KT to avoid dyslipidemia, which is a risk factor for cardiovascular disease. Well programmed dietary and/or exercise protocols to prevent muscle atrophy and fat gain should be considered even after successful KT.

Purpose. Successful kidney transplantation (KTx) can ameliorate bodily damage caused by end-stage renal disease (ESRD). Arterial stiffness (AS) is one of the critical factors that shorten the survival of patients due to cardiovascular events. KTx may reduce AS as well; however, this has not been investigated well. We therefore conducted a retrospective study using noninvasive pulse wave velocity (PWV), which is a useful index of aortic damage. Patients and methods. Fifty-eight consecutive kidney recipients (34 men, 24 women) were enrolled in this study. Mean age at transplantation was 40.5 +/- 12.3 years and the dialysis period was 73.1 +/- 95.8 months. The brachial-ankle PWV was measured preoperatively and 6 months postoperatively. First, we investigated the relationship between the PWV and the other parameters related to AS. Second, we studied the pre- to posttransplant change in PWV to evaluate the amelioration of AS after successful KTx. Results. PWV showed significant positive correlations with age, systolic blood pressure (BP), diastolic BP, and abdominal aortic calcification index. After successful KTx, PWV significantly decreased (P &lt; .01). In addition, systolic and diastolic BP significantly decreased (P &lt; .01 and P &lt; .05, respectively). Conclusion. Successful KTx ameliorates AS in ESRD patients. This might explain the improved cardiovascular prognosis of ESRD patients who undergo KTx.

生体腎移植術を施行したタクロリムス徐放性製剤(TACER)導入50例と従来製剤(TAC)導入50例、合計100例を対象に、TACERを用いた免疫抑制療法の短期成績をTACと比較検討した。免疫抑制レジメンはTACERまたはTACのほかミコフェノール酸モフェチル(MMF)、バシリキシマブを用い、ABO血液型不適合および既存抗ドナー抗体陽性以外は原則ステロイドを3日間で離脱した。TACERの初期投与量は0.1mg/kgを1日1回とし、TACは0.05mg/kgを1日2回とした。以後の投与量は血中濃度曲線下面積(AUC)に基づき調節した。移植腎機能については血清クレアチニン(sCr)は移植後6ヵ月迄の範囲で3週目と4週目ではTACER群でsCrが有意に高値であったが、観察期間全体では2群間に有意差はなかった。尿タンパクはTACER群で有意に低値であった。薬物動態の結果は、観察期間中CO、AUC共にTACER群においてTAC群より有意に低値であった。以上より、タクロリムスは高濃度では腎細動脈の攣縮により腎血流低下をきたし、尿細管毒性により腎障害をきたす。また、長期的には腎細動脈の硝子化による細動脈狭小化により慢性虚血性変化をきたすことが示唆された。

Background. The Japanese herbal medicine Tokishakuyaku-san (TJ-23) has been used to treat neurodegenerative, immune, and respiratory tract diseases, as well as many gynecologic disorders, with few adverse effects. This study investigated the effect of TJ-23 on alloimmune responses in a murine model of cardiac allograft transplantation. Methods. CBA mice underwent transplantation of a C57BL/6 heart and received oral administration of 2 g/kg per day of TJ-23 or 1 of 16 other commonly used Japanese herbal medicines from the day of transplantation until 7 days afterward. An adoptive transfer study was conducted to determine whether regulatory cells were generated. Histologic and cell proliferation studies, cytokine measurements, and flow cytometry analyses were also performed. Results. Of the 1 7 herbal medicines studied, only TJ-23, given in a dose of 2 g/kg per day, induced significantly prolonged allograft survival (median survival time [MST], &gt; 100 days). TJ-23 also suppressed proliferation of splenocytes and production of interleukin-2, interleukin-6, and interferon-gamma. Adoptive transfer of either whole splenocytes or CD4(+) or CD4(+) CD25(+) cells from TJ-23-treated allograft recipients resulted in indefinite survival of allografts in naive secondary recipients (MST &gt; 100 days). Flow cytometry studies showed that the CD4+ CD25(+) forkhead/winged-helix (FOXP3)(+) regulatory cell population was increased in transplant recipients given TJ-23. Conclusion. TJ-23 induced hyporesponsiveness to fully allogeneic cardiac allografts and generated C)4 CD25(+) regulatory cells in our model. (Surgery 2011;150: 923-33.)

Dietary intake of omega-3 polyunsaturated fatty acids (PUFAs) has been found to affect inflammation and metabolism, and many researchers have shown that omega-3 PUFAs provide benefits in immunologic and metabolic disorders. These effects were assumed to result mainly from a modification in the production of inflammatory mediators and the suppression of inflammatory leukocytes. Among PUFAs, eicosapentaenoic acid (EPA), a component of fish oil, apparently has the most potent effect. Recently, much research has focused on regulatory T cells (Tregs) as controllers of immune responses not only to self-antigens but also to non-self-antigens, including donor alloantigens. Therefore, induction of antigen-specific Tregs may be an attractive strategy for managing autoimmune diseases and transplant rejection. Peroxisome proliferator-activated receptor gamma (PPAR gamma), a ligand-activated nuclear receptor that regulates lipid and glucose metabolism. can be activated by thiazolidinediones, fatty acids, and eicosanoids, including EPA. PPAR gamma was recently found to have immunoregulatory effects, and a PPAR gamma agonist inhibited immune responses in a rat model of autoimmune disease. Furthermore, in a murine model, one high dose of purified EPA given the day of transplantation induced marked prolongation of cardiac allograft survival in a dose-dependent manner. These findings suggest that EPA induced Tregs by means of a PPAR gamma-dependent mechanism. This review describes the immunomodulatory effects of PUFAs, especially EPA, and summarizes recent research that may have implications for the development of therapies for autoimmune diseases and transplant rejection that are based on induction of Tregs. (c) 2010 Elsevier B.V. All rights reserved.

Background. We previously showed that pretreatment with intratracheal delivery (ITD) of alloantigen induced prolonged cardiac allograft survival and generated regulatory cells in mice. In this study, we examined the role of alveolar macrophages (AM) in our ITD model. Methods. Some CBA mice were given ITD of C57BL/6 splenocytes and underwent transplantation of C57BL/6 hearts 7 days later. In others, AM were depleted with clodronate-loaded liposomes 3 days before ITD. In adoptive transfer studies, whole splenocytes were obtained from ITD-treated CBA mice and administered to naive CBA secondary recipients, which were given C57BL/6 hearts immediately afterward. Interleukin-10 concentrations in bronchoalveolar lavage fluid were assessed by enzyme-linked immunosorbent assays. Immunohistologic and flow cytometric studies were performed after ITD. Results. C57BL/6 splenocytes given by ITD were ingested by AM in 2 days and undetectable in paratracheal lymph nodes or spleen tissue. CBA mice given ITD of C57BL/6 splenocytes had markedly prolonged allograft survival (median survival time [MST], 86 days), whereas naive CBA mice rejected allografts acutely (MST, 8 days). AM-depleted, ITD-treated mice also rejected allografts (MST, 5.5 days). Naive secondary recipients given adoptive transfer of splenocytes from ITD-treated mice had prolonged allograft survival (MST, &gt; 100 days), whereas secondary recipients given adoptive transfer of splenocytes from AM-depleted, ITD-treated mice rejected the grafts (MST, 15.5 days). Interleukin-10 expression in bronchoalveolar lavage fluid was down-regulated in AM-depleted mice compared with naive mice. Conclusions. AM have an important role in the induction of regulatory cells in our model of ITD of alloantigen.

腎移植患者に発症した慢性骨髄性白血病(CML)の報告は世界で10数例に過ぎない。今回この1例を経験したので報告する。症例は37歳男性。IgA腎症による腎不全にて9ヵ月の血液透析をへて生体腎移植施行。移植後の腎機能は徐々に悪化し当科に紹介された。移植3年3ヵ月後に白血球の著明な上昇を認め、骨髄生検を施行したところCMLの診断が得られた。イマチニブ投与が第一選択とされたが、タクロリムス(TAC)との薬剤相互作用を回避するためと、残腎機能がeGFR16ml/min/1.73mm2程度であったため、TACを中止しイマチニブ投与を開始した。その9日後に血液透析再導入となった。現在生存中であり、白血球は正常化し、BCR-ABL融合遺伝子は消失した状態を維持している。(著者抄録)

A 32-yr-old female patient, who had been suffering from diffuse crescentic glomerulonephritis and a consequent end-stage renal disease, successfully underwent living-related ABO-incompatible kidney transplantation after a desensitization therapy including anti-CD20 monoclonal antibody. Forty-six months after the transplantation, the recipient became pregnant. At the 17th gestational week, the patient was admitted for the management of pregnancy-induced hypertension and aggressive deterioration of kidney graft function. At the 21st gestational week, the patient lost her kidney graft and was re-induced into regular hemodialysis. The patient was also suffering from progressive hemolytic anemia, thrombocytopenia, and neurologic symptoms with decreased activity of von Willebrand factor-cleaving protease, a disintegrin-like and metalloprotease with thrombospondin type 1 motifs 13 (ADAMTS13). From these findings and a kidney allograft biopsy, the patient was diagnosed as thrombotic thrombocytopenic purpura concurrent with acute T-cell-mediated rejection. The patient immediately underwent plasma exchange as well as steroid pulse therapy. Despite these treatments, thrombocytopenia and intrauterine growth retardation progressed. The patient underwent a caesarian section at the 24th gestational week. Consequently, her platelet count recovered drastically. However, the patient lost her neonate five d after giving a birth, and the patient&apos;s graft function had never recovered.

Background. Ursodeoxycholic acid (UDCA) has been used to treat patients with cholestatic and autoimmune liver diseases. Several studies have addressed whether UDCA can inhibit graft rejection in experimental and clinical transplantation, but the results have varied. We investigated the effect of UDCA and the mechanism of its effect on alloimmune responses in a murine model of cardiac transplantation. Methods. CBA mice underwent transplantation of a C57BL/10 heart and received a single dose of UDCA. Survival times of the allografts were recorded. An adoptive transfer study was conducted to determine whether regulatory cells were generated. The effects on graft survival of adding FK506 or cyclosporine A (CyA) to UDCA treatment were assessed. Histologic, cell proliferation, and cytokine assessments were performed. Results. CBA recipients given UDCA (25 mg/kg) had indefinite allograft survival (median survival time [MST], &gt; 100 days). UDCA also suppressed proliferation of splenocytes and production of interleukin (IL)-2, IL-6, and interferon-gamma, and up-regulated IL-10 production. Adoptive transfer of either whole splenocytes or CD4(+) cells from UDCA-treated allograft recipients resulted in indefinite survival of allografts in naive secondary recipients (MST, &gt; 100 days). Adoptive transfer of CD4(+)CD25(+) cells from UDCA-treated recipients significantly prolonged allograft survival in naive secondary recipients (MST, &gt;80 days). FK506 (0.1 mg/kg/day) was compatible with the induction of indefinite allograft survival by UDCA, whereas CyA (10 mg/kg/day) abrogated the effect of UDCA. Conclusion. UDCA induced unresponsiveness to fully allogeneic cardiac allografts and generated CD4(+)CD25(+) regulatory cells in Our model. FK506, but not CyA, was compatible with UDCA treatment.

Sairei-to (TJ114), a 12-component Japanese herbal medicine, is used to treat immune-related diseases. We investigated the effects of oral administration of TJ114 in a murine model of cardiac transplantation with fully mismatched allografts. Untreated CBA mice rejected C57BL/6 hearts acutely (median survival time [MST], 7 days), whereas survival of allografts from mice given TJ114 was significantly prolonged (MST &gt; 100 days). Secondary CBA recipients of C57BL/6 hearts also had prolonged allograft survival (MST &gt; 100 days) after adoptive transfer of whole or CD4(+) splenocytes from primary CBA allograft recipients given TJ114. None of the individual components of TJ114 prolonged allograft survival, suggesting that its effects require administration of the combination agent. In mixed leukocyte Cultures, proliferation of splenocytes from TJ114-treated CBA recipients was markedly suppressed compared with that of splenocytes from untreated mice, and interferon-gamma production was significantly reduced. Thus, in our model, TJ114 treatment induced hyporesponsiveness to cardiac allografts and generated CD4(+) regulatory cells.

Fish oil, which is rich in eicosapentaenoic acid (EPA), has been found to have immunomodulatory effects. We examined whether administration of purified EPA affected survival of fully mismatched murine cardiac allografts. Hearts from C57BL/10 (H-2(b)) mice were transplanted into CBA (H-2(k)) recipients treated with one intraperitoneal dose of purified EPA the day of transplantation. Untreated CBA recipients and recipients given 0.1 g/kg of EPA rejected C57BL/10 hearts (median survival time [MST], 8 and 13 days, respectively). With a 1.0 g/kg dose of EPA, graft survival was markedly prolonged (MST &gt; 100 days). To determine whether regulatory cells were generated, naive mice (secondary recipients) underwent adoptive transfer of splenocytes from EPA-treated primary recipients and cardiac allograft transplantation. Adoptive transfer of whole, CD4(+) and CD4(+)CD25(+) splenocytes from EPA-treated recipients induced indefinite survival in secondary recipients. Flow cytometry showed that the CD4(+)CD25(+) cells were Foxp3(+). In reverse transcriptase-polymerase chain reaction (RT-PCR) studies, the expression of peroxisome proliferator-activated receptor gamma (PPAR gamma) mRNA was upregulated by EPA treatment. A PPAR gamma antagonist abrogated the prolongation of graft survival induced by EPA treatment (MST, 13 days). Thus, in our model, purified EPA induced prolonged survival of fully mismatched cardiac allografts and generated regulatory T cells dependent on PPAR gamma activation.

A 40-year-old woman who had been suffering from type II diabetes mellitus and consequent end-stage renal disease underwent living related kidney transplantation. The graft renal artery was anastomosed to the right internal iliac artery (end-to-end). Postoperative renoscintigraphy demonstrated normal graft perfusion. The serum lactate dehydrogenase level increased abruptly at postoperative day 15 and digital subtraction angiography disclosed graft artery thrombosis. Despite an intervention using a metallic coil stent, the rapid formation of thrombus occluded the graft artery completely. In an emergent surgical operation, the graft was nephrectomized carefully and irrigated after extensive thrombectomy. The graft was reimplanted by using an internal iliac artery graft. After three consecutive hemodialysis treatments, the patient&apos;s kidney graft functioned well. She has been in good health with stable graft function for 3 years after the operation.

The aim of the current study was to evaluate long-term outcomes of pediatric live kidney transplantation in patients with genitourinary anomalies relative to those with primary kidney diseases. The study included 35 pediatric patients who received a live kidney transplantation during the last 25 yr (28 males, six females). Median age at the time of transplantation was nine yr (range 1-15 yr), and the median follow-up period was 151 months (range 6-239 month). The patients were divided into two groups. The urological group (n = 14) included patients with primary obstructive/reflux nephropathy. The renal group (n = 20) included patients with primary renal disorders. Differences between groups in graft survival, clinical course, and final graft function were evaluated. Original diseases represented in the urological group included five cases with primary VUR and eight cases with secondary VUR. Diseases in the renal group included eight cases with bilateral hypo-dysplastic kidney, three cases with focal/segmental glomerular sclerosis, two cases with membranous proliferative glomerulonephritis, two cases with congenital nephrotic syndrome and five cases with other forms of chronic nephritis. Ten of 14 cases in the urological group, relative to six of 20 in the renal group, were preemptive. Median age at transplantation was 7.5 or 10 yr old, respectively, in the urological or renal group. Twelve kidney recipients in the urological group had also undergone other urinary surgeries, including upper urinary tract drainage, ureteroneocystostomy, augmentation cystoplasty, endoscopic incision of posterior-urethral valve, urethroplasty, etc. Cumulative post-operative complications occurred in nine or 16, respectively, in the urological or renal group. The acute rejection free and overall graft survival were similar in both groups. One patient in the urological group lost his graft while six patients in the renal group lost their grafts. Thus, the post-transplant clinical outcome of pediatric transplantation in patients with urological anomalies is comparable to that of recipients with primary renal disease. Appropriate urinary tract reconstruction and management is essential to reduce the risk of graft dysfunction because of urinary problems.