伊藤 泰平

2001～2121年度の膵臓移植474例のうち膵移植後の抗体関連型拒絶反応(ABMR)に対し免疫グロブリン静注療法(IVIG)を用いた4例(男性2例、女性2例、移植時年齢40代3例、50代1例)について調査した。原疾患は4例全てI型糖尿病で、糖尿病性腎症の合併による血液透析中2例、腎移植後2例であった。観察期間中、全例で抗ドナー特異抗体(DSA)陽性を認めた。転帰は、ABMRを制御できず膵・腎グラフトを摘出しインスリン、透析再導入1例、膵グラフト生着3例のうち1例はABMR発症後にインスリン再導入となった。IVIG治療による有害事象は無く、治療後1年時点で全例生存しており生命予後は良好であった。

OBJECTIVES: About 90% of Japanese kidney transplantations are conducted from living donors, and their safety and the maintenance of their renal function are critical. This study aims to identify factors that affect the compensation of renal function in living kidney donors after donor nephrectomy. METHOD: In a retrospective cohort study, we reviewed data from 120 patients who underwent nephrectomy as living kidney transplant donors in our department from 2012 to 2021. Univariable and multivariable linear regression analyses were performed for donor factors affecting renal function after donor nephrectomy. RESULT: The multivariable linear regression model revealed that the donor's age (p = 0.025), preoperative estimated Glomerular Filtration Rate (eGFR) (p < 0.001), and hemoglobin A1c (HbA1c) (p = 0.043) were independent risk factors for eGFR at six months after nephrectomy. The eGFR deterioration was more strongly associated with age in females than in males, whereas higher HbA1c values were more strongly associated with eGFR deterioration in males. Higher donor age and higher HbA1c each enhance the deterioration of eGFR six months after living donor nephrectomy. The data suggest that old age in especially female donors and preoperative higher HbA1c in male donors have a harmful impact on their renal function compensation.

OBJECTIVES: Type 1 diabetes mellitus (T1DM) patients with diabetic kidney disease-induced kidney failure have a significantly impaired quality of life (QOL), resulting in a high level of physical, mental, and social anxiety. In this study, we evaluated the QOL of T1DM patients on the list for pancreas transplantation (PTx) at their registration, and determined whether PTx improved their QOL. METHODS: There were 58 patients (men/women, 22/36; mean age, 42.8±8.0 years) with T1DM and who were registered on the waiting list for PTx. Quantitative QOL assessment was performed using the Medical Health Survey Short Form (SF-36) version 2. Changes in the QOL before and after PTx were also examined in 24 of these patients. RESULTS: The mean value of each endpoint and the summary score of the SF-36 physical (PCS), mental (MCS), and role (RCS) components were all below the national normal level at PTx registration. No significant difference in QOL scores was observed in the intergroup comparison of 35 patients on dialysis, 13 patients without dialysis, and ten patients after kidney transplantation. The 24 patients who underwent PTx showed improvement in PCS, MCS, and most SF-36 scores. CONCLUSION: T1DM patients waiting for PTx had a decreased QOL, regardless of dialysis, and PTx improved their QOL.

BACKGROUND: Because of the organ shortage, donation after cardiac death (DCD) kidney transplantation (KTx) is an alternative way of achieving KTx using brain-dead donors (BDs). Although the prognosis of DCD-KTx is improving, the graft suffers from delayed graft function (DGF), the management of which is essential. With progress in understanding the characteristics of cell-free DNA (CF-DNA), we consider plasma total CF-DNA (tCF-DNA) to be a useful biomarker for predicting DGF in DCD-KTx. STUDY DESIGN AND METHOD: Consecutive patients from living donors (LDs; n = 9), BDs (n = 8), or DCD donors (n = 13) were enrolled. Plasma samples were collected after KTx and on postoperative days 3 and 5. CF-DNA was isolated, and tCF-DNA was quantified using the TapeStation 2200 software program. RESULTS: The tCF-DNA levels after BD-KTx and DCD-KTx were higher than those after LD-KTx (LD, 78 ± 27 (ng/mL); BD, 99 ± 20; DCD, 150 ± 23); the difference between DCD-KTx and LD-KTx was statistically significant (P < .05). The tCF-DNA levels declined at postoperative day 5 (LD, 45 ± 10; BD, 51 ± 11; DCD, 66 ± 13). tCF-DNA levels were significantly increased in patients with DGF after KTx (DGF, 139 ± 22; immediate function, 91 ± 18; P < .05). The tCF-DNA level was correlated with the duration of DGF (r = 0.5825, P < .05). CONCLUSION: Although the mechanism underlying DNA release from transplanted grafts into the recipient circulation remains unclear, cell death by apoptosis or necrosis and the active secretion of the immune system may play important roles in DGF. These data suggest that monitoring tCF-DNA may help predict graft recovery after DCD-KTx.

OBJECTIVES: Delta C-peptide derived by the glucagon stimulation test is a reliable value for the evaluation of the pancreatic endocrine function after pancreas transplantation. We examined the associations between delta C-peptide as pancreatic graft endocrine function and donor background factors. METHODS: Sixty-five cases of pancreatic transplantation from brain-dead donors, which were performed in our facility, were enrolled in this study. Enrolled recipients underwent a glucagon stimulation test within 1 to 3 months after transplantation to evaluate the pancreatic graft endocrine function with delta C-peptide to compare donor background factors. RESULTS: The following factors were associated with significant deterioration of the delta C-peptide: age of 50 years or greater, death from cerebrovascular accident, hemoglobin A1c level of 5.6% or greater, creatinine level of 1.0 mg/dL or greater, C-reactive protein level of 25 mg/dL or greater, and sodium level of 150 mmol/L or greater. In addition, increased numbers of these donor factors indicated significantly greater deterioration of the posttransplant pancreatic endocrine function (P < 0.001). CONCLUSIONS: To secure insulin independence after pancreas transplantation, which means maintaining a delta C-peptide level of 1.0 ng/mL or greater on a glucagon stimulation test, the utilization of donors, who possesses more than equal to 3 of the donor factors identified in this study, should be carefully considered.

脳死下・心停止後臓器摘出における勤務実態と就労管理・補償・待遇の現状に関する日本移植学会アンケート調査より、膵臓移植における移植時レシピエント年齢と移植後予後との関連性について報告した。解析対象は過去約19年間の膵臓移植症例379例(24〜69歳、中央値44歳)で、経過観察期間は6日〜18.8年(中央値4.95年)であった。レシピエントを50歳未満285例(若年群)と50歳以上94例(高齢群)に分け、傾向スコアマッチングによる検討を行った。結果、移植後1年以内の死亡率は年齢の上昇に伴って高くなる傾向を認め、高齢群は若年群と比較して死亡率が高かった。また、糖尿病歴は若年群では予後に影響していなかったが、高齢群では予後に影響を与えていた。

BACKGROUND: In Japan, donations after circulatory death kidney transplantation are widely performed due to legislation delays. The number of donations after brain death kidney transplantations is increasing, but the target remains unmet. We reviewed the outcomes of donation after circulatory death in Japan. METHODS: We analyzed 2923 deceased kidney transplantations (2239: donation after circulatory death (DCD), 684: donation after brain death (DBD)) performed in Japan from 2000 to 2019. The outcomes of the DCD and DBD groups were compared. We examined the risk factors for graft loss in the DCD group. RESULTS: The 5-year patient survival and death-censored graft survival rates of the DCD group, obtained by propensity score matching, were 93.6% and 95.2%, respectively, which were equivalent to 94.2% and 93.8%, respectively, obtained in the DBD group. Older donors (≥ 50 years) and prolonged cold ischemia time (≥ 12 h) were risk factors for graft loss; in the presence of these, graft survival was lower in the DCD group. CONCLUSIONS: Older donors and prolonged cold ischemia time reduced graft survival in the DCD group. Proper evaluation of donors and careful preparation for transplant surgery are, therefore, essential to ensure good transplant outcomes.

膵移植後に抗体関連型拒絶反応(AMR)を発現し、rituximabを使用した4例を報告した。移植時年齢は30歳代から50歳代で、男女各2例であった。AMRは移植後40日目から143日目に診断され、rituximabは拒絶反応発現から最短で1日、最長で20日に1回投与されていた。投与量は81mg/bodyが1例、200mg/bodyが3例で、AMR治療後の膵グラフト生着は1例(25%)で得られていた。有害事象としてはサイトメガロウイルス抗原血症による感染症が1例、骨髄抑制が2例で認められたが、いずれも回復し、患者生命予後に影響を与える有害事象はみられなかった。

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

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

【背景】膵臓移植においてレシピエント年齢が移植成績に与える影響は明らかではない。本邦登録データを用いて、レシピエント年齢と移植後予後との関連性について検討した。【対象・方法】2000年から2019年4月までに施行された379例（生体を除く）の膵臓移植患者を後方視的に検討した。主要評価項目を患者生存期間とし、比例ハザードモデルに基づき50歳をカットオフとし若年群（n=285）と高齢群（n=94）とに群別。両群間の患者背景を傾向スコアでマッチさせ、生存期間、術後合併症、死因を比較した。また高齢群における予後因子を検討した。【結果】傾向スコアマッチ後、高齢群(n=77)の５年生存率は86.9%と、若年群(n=77)の97.1%と比べ有意に低かった(P= 0.026)。一方、グラフト生着率、術後合併症発生率においては両群に有意な差は認めなかった。死因別では高齢群で感染または多臓器不全、心・脳血管系イベントが有意に多く、高齢群で観察期間中に死亡した16例のうち10例は術後1年以内であった。多変量解析の結果、高齢群における術後1年以内の死亡リスク因子は糖尿病罹患期間であった（P= 0.005）。【結語】50歳以上のレシピエントに対する膵臓移植は、50歳未満と比較して有意に移植後の生存率が不良であるが、糖尿病歴が短い症例ほど生存率が改善する可能性が示唆され、より早期の移植が望ましいと考えられた。

De novo renal cell carcinoma (RCC) rarely occurs in kidney allografts; however, the risk of RCC in these patients is 100-fold that of the general healthy population. Although total nephrectomy has been the standard treatment for kidney allograft RCC, several authors have reported that early-stage RCC in kidney allografts was successfully treated with nephron-sparing surgery. We herein describe a new procedure involving renal autotransplantation and extracorporeal nephron-sparing surgery, which was performed to treat de novo RCC near the hilum of a transplanted kidney. In the 22 months since transplantation, the patient's renal function has been favorable, and no recurrence has been observed. In conclusion, renal autotransplantation is a feasible technique for the treatment of RCC in kidney allografts, especially RCC located near the hilum.

腎移植患者19名(男性14名、女性5名、献腎移植7名・生体腎移植12名)を対象に、消化器悪性腫瘍に対し末梢血液全血細胞を用いた網羅的遺伝子発現解析を行い、スクリーニング検査としての有用性について検討した。なお、移植時年齢は23〜64歳(中央値46歳)、検査時年齢は33〜70歳(中央値54歳)、悪性腫瘍の既往は腎癌3例、骨肉腫と甲状腺癌1例、子宮頸癌1例、悪性リンパ腫1例であった。遺伝子変動数が陽性と判断されたのは19回、境界が18回、陰性が16回であった。健常人と比べたところ、腎移植患者においては有意に増加していた。21遺伝子のパターン分析から境界と判断されたのは25回、陰性が28回であった。階層クラスタリング解析により陽性と判断されたのは2回、境界が11回、陰性が40回であった。アルゴリズムを用い、胃/大腸癌、膵臓癌、胆道癌の有無を判別し、最終的に陽性と判断された例はなかった。