星長 清隆

ラット腎瘢痕モデルを作製して腎瘢痕形成に関わる網羅的遺伝子解析を行い、発現の持続亢進が認められたNGAL(Neutrophil gelatinase-associated lipocalin)に着目し、VUR児における腎瘢痕バイオマーカーとしての有用性について検討した。検討方法は、VUR児群(34例)と正常児群(28例)とで尿中NGAL値を比較した。また、VUR児群のみを対象とし、腎瘢痕の有無と尿中NGAL値との関連性について他のマーカー(血清クレアチニン、尿中BMG、尿中NAG)と比較した。結果、正常児群に比べてVUR児群は尿中NAGLが有意に高値であった。腎瘢痕の有無との関連では、尿中NGALは他のマーカーに比べて特異度が高かった。

原発性の膀胱尿管逆流(VUR)の治療を施行され、現在20歳以上となった61例のうち、長期フォローアップを行った41例を対象に、患者背景、逆流の程度、腎瘢痕の程度、外科的治療後の腎機能の変化、逆流性腎症発症例および予後を調査した。手術時年齢は平均4.9歳で、術後の平均観察期間は18.7年であった。その結果、1例を除き外科的治療が施行されていた。経過観察中に逆流性腎症を41例中8例(19.5%)に認め、そのうち手術例7例の逆流性腎発症までの術後期間は平均10.7年であった。高度逆流(IV以上)、腎瘢痕(特にdysplasiaを有する場合)、診断または手術時年齢が高い、性差(女性)で高血圧や蛋白尿、CRDが多く認められた。原発性VURの逆流性腎症の発症率は約20%であったが、発症までの期間は長く、長期フォローアップの必要性があると思われた。また、逆流性腎症のリスク因子は高度逆流、腎瘢痕、低形成腎を有する症例、手術(診断)時間、性差と考えられた。

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。

<p>【Objective】Kidney transplant recipients are at increased risk of developing cancer in comparison with the general population. To effectively manage post-transplant malignancies, it is essential to proactively monitor patients. A long-term intensive screening program was associated with a reduced incidence of cancer after transplantation. This study evaluated the usefulness of the gene expression profiling of peripheral blood samples obtained kidney transplant patients and adopted a screening test for detecting cancer of the digestive system (gastric, colon, pancreas and biliary tract cancer).<br/>【Methods】Nineteen patients were included in this study, and a total of fifty-three gene expression screening tests were performed. The gene expression profiles of blood-delivered total RNA and whole genome human gene expression profiles were obtained. We investigated the expression levels of 2,665 genes associated with digestive cancers and counted the number of genes in which expression was altered. A hierarchical clustering analysis was also performed. The final prediction of the cancer possibility was determined according to an algorithm.<br/>【Results】The number of genes in which expression was altered was significantly increased in the kidney transplant recipients in comparison to the general population (1,091±63 vs. 823±94, p=0.0024). The number of genes with altered expression decreased after the induction of mTOR inhibitor (1,484±227 vs. 883±154, p=0.0439). No cases of possible digestive cancer were detected in this study period.<br/>【Conclusion】The gene expression profiling of peripheral blood samples may be a useful and non-invasive diagnostic tool that allows for the early detection of cancer of the digestive system.</p>

A 53-year-old woman who had undergone deceased donor kidney transplantation twice, at 35 and 43 years of age, presented with renal impairment. She was infected with hepatitis C virus (HCV). The histology of the graft kidney revealed post-transplant membranous nephropathy (MN) with podocytic infolding and antibody-mediated rejection (AMR). IgG subclass staining showed fine granular deposits of IgG1 and IgG3, but not IgG4, in the glomerular capillary walls. Panel reactive antibody scores for human leukocyte antigen class I and class II were 92.67% and 66.68%, respectively. Thus, this case of post-transplanted MN was considered to be associated with AMR and HCV infection.<br>