Viral life cycle and the diagnosis of BK polyomavirus-associated nephropathy.

• Project/Area Number: 16K11066
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Fukuoka University (2017-2018); Kyushu University (2016)
• Principal Investigator: Masutani Kosuke 福岡大学, 医学部, 准教授 (30419593)
• Co-Investigator(Kenkyū-buntansha): 鶴屋 和彦 奈良県立医科大学, 医学部, 教授 (20372740) ; 土本 晃裕 九州大学, 大学病院, 助教 (50572103)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: BK polyomavirus / 腎移植 / 病理 / BKウイルス腎症 / 病理組織診断 / 免疫組織染色 / SV40 large-T抗原 / VP1蛋白 / ウイルス感染症

Outline of Final Research Achievements

We performed immunohistochemical staining for SV40 TAg and VP1 in 28 biopsies of BKPyVAN, and compared the patterns of positivity and the percentage of positive tubules. We investigated the correlation between Cr increase and the percentage of positive tubules for both markers. In VP1 staining, positive findings were observed not only in the nuclei of tubular epithelial cells, but also in the cytoplasm, cells shedding into the lumen, intratubular casts. Two of 28 biopsies (7.1%) showed TAg-positive and VP1-negative results. The median percentage of positive tubules was 2.8% for TAg, and 1.4% for VP1 staining (P=0.2). Cr increases significantly correlated with the percentage of VP1-positive tubules (r=0.49, P=0.02), while this correlation revealed borderline significance in TAg staining. VP1 expression showed various patterns, but was detected in half as many tubules as TAg staining, which might lead to false negatives in the samples with minimal viral replication.

Academic Significance and Societal Importance of the Research Achievements

VP1染色は多彩な陽性所見を呈し、視認性も良好であったが、陽性尿細管数で見ると古典的なSV40 TAg染色の半数の尿細管を検出し、感染尿細管が非常に少ない検体では偽陰性の可能性もある。従って腎症の診断の感度としてはSV40 TAg染色を超えることはないと考えられる。ただし、VP1陽性尿細管が多い症例ほど血清Cr値の上昇が大きいことから、治療経過や予後をより反映する可能性がある。Banff Working GroupがTAg染色をベースとした新しいBKウイルス腎症のステージ分類を発表しているが、予後予測能力については染色法も含め更なる検討が必要と考えられる。

Research Products

• [Journal Article] Hemoglobin Concentrations and the Risk of Hemorrhagic and Ischemic Stroke in Patients Undergoing Hemodialysis: The Q-Cohort Study. (2018)
  • Author(s): Yotsueda R, Tanaka S, Taniguchi M, Fujisaki K, Torisu K, Masutani K, Hirakata H, Kitazono T, Tsuruya K.
  • Journal Title: Nephrol Dial Transplant Volume: 33 Issue: 5 Pages: 856-864
  • DOI: 10.1093/ndt/gfx305
  • Peer Reviewed
• [Journal Article] Association between serum albumin level and incidence of end-stage renal disease in patients with immunoglobulin A nephropathy: A possible role of albumin as an antioxidant agent. (2018)
  • Author(s): Kawai Y, Masutani K, Torisu K, Katafuchi R, Tanaka S, Tsuchimoto A, Mitsuiki K, Tsuruya K, Kitazono T.
  • Journal Title: PLoS One Volume: 13 Issue: 5 Pages: e0196655-e0196655
  • DOI: 10.1371/journal.pone.0196655
  • Peer Reviewed
• [Journal Article] Secular trends in the incidence of end-stage renal disease and its risk factors in Japanese patients with immunoglobulin A nephropathy. (2018)
  • Author(s): Tanaka S, Ninomiya T, Katafuchi R, Masutani K, Tsuchimoto A, Tokumoto M, Hirakata H, Ooboshi H, Kitazono T, Tsuruya K
  • Journal Title: Nephrol Dial Transplant Volume: 印刷中 Issue: 6 Pages: 963-971
  • DOI: 10.1093/ndt/gfx223
  • Peer Reviewed
• [Journal Article] The effect of steroid pulse therapy on post-transplant immunoglobulin A nephropathy. (2018)
  • Author(s): Matsukuma Y, Masutani K, Tsuchimoto A, Okabe Ym Nakamura M, Tsuruya K、Kitazono T.
  • Journal Title: Nephrology Volume: 23 (Suppl 2) Issue: S2 Pages: 305-312
  • DOI: 10.1111/nep.13272
  • Peer Reviewed
• [Journal Article] Study on dialysis session length and mortality in maintenance hemodialysis patients: The Q-Cohort Study. (2018)
  • Author(s): Fujisaki K, Tsuruya K, Tanaka S, Taniguchi M, Masutani K, Hirakata H, Kitazono T.
  • Journal Title: Nephron Volume: 139 Issue: 4 Pages: 305-312
  • DOI: 10.1159/000489680
  • Peer Reviewed
• [Journal Article] Evaluation of the effects of chronic kidney disease and hemodialysis on the inner ear using multifrequency tympanometry. (2018)
  • Author(s): Tamae A, Ishizu K, Yoshida T, Kubo K, Matsumoto N, Yasui T, Masutani K, Tsuruya K, Nakagawa T.
  • Journal Title: J Int Adv Otol Volume: 14 Issue: 3 Pages: 447-450
  • DOI: 10.5152/iao.2018.4736
  • Peer Reviewed / Open Access
• [Journal Article] Regional variations in immunosuppressive therapy in patients with primary nephrotic syndrome: the Japan nephrotic syndrome cohort study. (2018)
  • Author(s): Yamamoto R, Imai E, Maruyama S et al.
  • Journal Title: Clin Exp Nephrol Volume: 22 Issue: 6 Pages: 1266-1280
  • DOI: 10.1007/s10157-018-1579-x
  • Peer Reviewed
• [Journal Article] Preformed C1q-binding donor-specific anti-HLA antibodies and graft function after kidney transplantation. (2018)
  • Author(s): Okabe Y, Noguchi H, Miyamoto K, Kaku K, Tsuchimoto A, Masutani K, Nakamura M.
  • Journal Title: Transplant Proc Volume: 50 Issue: 10 Pages: 3460-3466
  • DOI: 10.1016/j.transproceed.2018.07.033
  • Peer Reviewed
• [Journal Article] The association of pre-dialysis blood pressure levels with the risk of all-cause mortality, and cardiovascular events in hemodialysis patients: The Q-Cohort Study. (2018)
  • Author(s): Hara M, Tanaka S, Taniguchi M, Fujisaki K, Torisu K, Masutani K, Hirakata H, Nakano T, Tsuruya K, Kitazono T.
  • Journal Title: Medicine Volume: 97 Issue: 51 Pages: e13485-e13485
  • DOI: 10.1097/md.0000000000013485
  • Peer Reviewed
• [Journal Article] Incidence of Hepatitis B Viral Reactivation After Kidney Transplantation With Low-Dose Rituximab Administration. (2018)
  • Author(s): Masutani K, Omoto K, Okumi M, Okabe Y, Shimizu T, Tsuruya K, Kitazono T, Nakamura M, Ishida H, Tanabe K; Japan Academic Consortium of Kidney Transplantation (JACK) Investigators.
  • Journal Title: Transplantation Volume: 102 Issue: 1 Pages: 140-145
  • DOI: 10.1097/tp.0000000000001870
  • Peer Reviewed
• [Journal Article] Rationale and study design of a clinical trial to assess the effects of LDL apheresis on proteinuria in diabetic patients with severe proteinuria and dyslipidemia. (2017)
  • Author(s): Wada T, Muso E, Maruyama S, Hara A, Furuichi K, Yoshimura K, Miyazaki M, Sato E, Abe M, Shibagaki Y, Narita I, Yokoyama H, Mori N, Yuzawa Y, Matsubara T, Tsukamoto T, Wada J, Ito T, Masutani K, Tsuruya K, Fujimoto S, Tsuda A, Suzuki H, Kasuno K, Terada Y, Nakata T, Iino N, Kobayashi S.
  • Journal Title: Clin Exp Nephrol Volume: - Issue: 3 Pages: 591-596
  • DOI: 10.1007/s10157-017-1488-4
  • Peer Reviewed / Open Access
• [Journal Article] The potential role of perivascular lymphatic vessels in preservation of kidney allograft function. (2017)
  • Author(s): Tsuchimoto A, Nakano T, Hasegawa S, Masutani K, Matsukuma Y, Eriguchi M, Nagata M, Nishiki T, Kitada H, Tanaka M, Kitazono T, Tsuruya K.
  • Journal Title: Clin Exp Nephrol Volume: 21 Issue: 4 Pages: 721-731
  • DOI: 10.1007/s10157-016-1338-9
  • Peer Reviewed
• [Journal Article] Cardiothoracic Ratio and All-Cause Mortality and Cardiovascular Disease Events in Hemodialysis Patients: The Q-Cohort Study. (2017)
  • Author(s): Yotsueda R, Taniguchi M, Tanaka S, Eriguchi M, Fujisaki K, Torisu K, Masutani K, Hirakata H, Kitazono T, Tsuruya K.
  • Journal Title: Am J Kidney Dis Volume: 70 Issue: 1 Pages: 84-92
  • DOI: 10.1053/j.ajkd.2016.11.026
  • Peer Reviewed
• [Journal Article] Association between serum uric acid level and renal arteriolar hyalinization in individuals without chronic kidney disease. (2017)
  • Author(s): Matsukuma Y, Masutani K, Tanaka S, Tsuchimoto A, Haruyama N, Okabe Y, Nakamura M, Tsuruya K, Kitazono T.
  • Journal Title: Atherosclerosis Volume: 266 Pages: 121-127
  • DOI: 10.1016/j.atherosclerosis.2017.09.017
  • Peer Reviewed
• [Journal Article] Vascular endothelial growth factor-C ameliorates renal interstitial fibrosis through lymphangiogenesis in mouse unilateral ureteral obstruction. (2017)
  • Author(s): Hasegawa S, Nakano T, Torisu K, Tsuchimoto A, Eriguchi M, Haruyama N, Masutani K, Tsuruya K, Kitazono T.
  • Journal Title: Lab Invest Volume: 97 Issue: 12 Pages: 1439-1452
  • DOI: 10.1038/labinvest.2017.77
  • Peer Reviewed
• [Journal Article] Impact of blood urea nitrogen to creatinine ratio on mortality and morbidity in hemodialysis patients: The Q-Cohort Study. (2017)
  • Author(s): Tanaka S, Ninomiya T, Taniguchi M, Tokumoto M, Masutani K, Ooboshi H, Kitazono T, Tsuruya K.
  • Journal Title: Sci Rep Volume: 7 Issue: 1 Pages: 14910-14910
  • DOI: 10.1038/s41598-017-14205-2
  • Peer Reviewed / Open Access
• [Journal Article] A J-shaped association between serum uric acid levels and poor renal survival in female patients with IgA nephropathy. (2017)
  • Author(s): Matsukuma Y, Masutani K, Tanaka S, Tsuchimoto A, Fujisaki K, Torisu K, Katafuchi R, Hirakata H, Tsuruya K, Kitazono T.
  • Journal Title: Hypertens Res Volume: 40 Issue: 3 Pages: 291-297
  • DOI: 10.1038/hr.2016.134
  • Peer Reviewed
• [Journal Article] Extended swan-neck catheter with upper abdominal exit-site reduces peritoneal dialysis-related infections. (2016)
  • Author(s): Eriguchi M, Tsuruya K, Yoshida H, Haruyama N, Tanaka S, Tsuchimoto A, Fujisaki K, Torisu K, Masutani K, Kitazono T.
  • Journal Title: Therapeutic Apheresis and Dialysis Volume: 20 (2) Issue: 2 Pages: 158-164
  • DOI: 10.1111/1744-9987.12358
  • Peer Reviewed
• [Journal Article] Comparison of steroid-pulse therapy and combined with mizoribine in IgA nephropathy: a randomized controlled trial. (2016)
  • Author(s): Masutani K, Tsuchimoto A, Yamada T, Hirakawa M, Mitsuiki K, Katafuchi R, Hirakata H, Kitazono T, Tsuruya K; West Japan Study Group for Therapy of IgA Nephropathy Investigators.
  • Journal Title: Clin Exp Nephrol Volume: 20 Issue: 6 Pages: 896-903
  • DOI: 10.1007/s10157-016-1226-3
  • Peer Reviewed
• [Journal Article] The effect of renin-angiotensin system blockade on the incidence of end-stage renal disease in IgA nephropathy. (2016)
  • Author(s): Tanaka S, Ninomiya T, Katafuchi R, Masutani K, Nagata M, Tsuchimoto A, Hirakata H, Kitazono T, Tsuruya K.
  • Journal Title: Clin Exp Nephrol Volume: 20 Issue: 5 Pages: 689-698
  • DOI: 10.1007/s10157-015-1195-y
  • Peer Reviewed
• [Journal Article] Light Chain Deposition Disease in an Older Adult Patient Successfully Treated with Long-term Administration of Bortezomib, Melphalan and Prednisone (2016)
  • Author(s): Hiyamuta H, Yamada S, Matsukuma Y, Tsuchimoto A, Nakano T, Taniguchi M, Masutani K, Yoshimoto G, Muta T, Akashi K, Kitazono T, Tsuruya K.
  • Journal Title: Internal Medicine Volume: 55 Issue: 10 Pages: 1319-1325
  • DOI: 10.2169/internalmedicine.55.5752
  • NAID: 130005151169
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed
• [Presentation] BKV腎症における large-T抗原染色とVP1染色の検討. (2019)
  • Author(s): 升谷耕介, 松隈祐太, 土本晃裕, 岡部安博, 土井篤, 加来啓三, 中野敏昭, 中村雅史, 北園孝成.
  • Organizer: 第52回日本臨床腎移植学会
• [Presentation] 腎移植後再発腎炎 up to date. (2019)
  • Author(s): 升谷耕介
  • Organizer: 第52回日本臨床腎移植学会
• [Presentation] 行列のできるスキルアップセミナー, 腎移植後のBKウイルス腎症～臨床医の悩みと検査部門への期待～. (2018)
  • Author(s): 升谷耕介
  • Organizer: 第67回日本医学検査医学会
• [Presentation] シンポジウム「腎代替療法における腎臓内科医の立場」：わが国における成人先行的腎移植の特徴 ～糖尿病と夫婦間移植を中心に～. (2018)
  • Author(s): 升谷耕介
  • Organizer: 第63回日本透析医学会学術集会
• [Presentation] シンポジウム「腎移植後の長期生存をめざすには（DWFG）」：腎移植前後の脂質異常症. (2018)
  • Author(s): 升谷耕介
  • Organizer: 第54回日本移植学会総会
• [Presentation] Predictive value of the combination of peripheral blood lymphocyte count and urinary cytology in the diagnosis of Polyomavirus BK nephropathy. (2018)
  • Author(s): Masutani K, Tsuchimoto A, Matsukuma Y, Kaku K, Kurihara K, Okabe Y, Tsuruya K, Nakamura M, Kitazono T.
  • Organizer: Transplantation Scientific Symposium, Asian Regional Meeting 2018
• [Presentation] 先行的腎移植の普及に向けて～移植施設の腎臓内科医が果たすべき役割～． (2017)
  • Author(s): 升谷耕介
  • Organizer: 第105回日本泌尿器科学会総会
• [Presentation] 腎移植後BKウイルス腎症における末梢血リンパ球数の検討. (2017)
  • Author(s): 升谷耕介、土本晃裕、松隈祐太、野口浩司、加来啓三、栗原啓、岡部安博、中村雅史、鶴屋和彦、北園孝成．
  • Organizer: 第60回日本腎臓学会学術総会
• [Presentation] 臓器移植後BKウイルス感染の診療ガイド作成の進捗状況． (2017)
  • Author(s): 升谷耕介
  • Organizer: 第52回日本移植学会総会
• [Presentation] 高齢腎移植患者における免疫抑制療法と合併症対策． (2017)
  • Author(s): 升谷耕介．
  • Organizer: 第51回日本臨床腎移植学会
• [Presentation] 腎移植後BKウイルス腎症における末梢血リンパ球数の検討． (2017)
  • Author(s): 升谷耕介、土本晃裕、松隈祐太、野口浩司、加来啓三、栗原啓、岡部安博、中村雅史、鶴屋和彦、北園孝成．
  • Organizer: 第51回日本臨床腎移植学会
• [Presentation] Early Complications After Kidney Transplantation: Current Screening, Diagnosis and Treatment. (2017)
  • Author(s): Masutani K.
  • Organizer: APSN/JSN CME course 2017,
  • Int'l Joint Research
• [Presentation] Predictive value of the combination of peripheral blood lymphocyte count and urinary cytology in the diagnosis of Polyomavirus BK nephropathy. (2017)
  • Author(s): Masutani K, Tsuchimoto A, Matsukuma Y, Kaku K, Kurihara K, Okabe Y, Tsuruya K, Nakamura M, Kitazono T.
  • Organizer: American Society of Nephrology, Kidney Week 2017
  • Int'l Joint Research
• [Presentation] Incidence of hepatitis B virus reactivation after kidney transplantation with low-dose rituximab administration. (2017)
  • Author(s): Masutani K, Omoto K, Okumi M, Okabe Y, Shimizu T, Tsuruya K, Kitazono T, Nakamura M, Ishida H, Tanabe K and the Japanese Academic Consortium of Kidney Transplantation (JACK) Investigators.
  • Organizer: American Society of Nephrology, Kidney Week 2017
• [Presentation] 腎移植後BKウイルス腎症における 末梢血リンパ球数の検討 (2016)
  • Author(s): 升谷耕介, 土本晃裕, 松隈祐太, 加来啓三, 野口浩司 , 栗原 啓, 岡部安博, 中村雅史, 鶴屋和彦, 北園孝成
  • Organizer: 第52回日本移植学会総会
  • Place of Presentation: 東京都
  • Year and Date: 2016-09-29
• [Presentation] B型肝炎ウイルス既感染腎移植レシピエント に対するリツキシマブ投与とウイルス 再活性化の検討 (2016)
  • Author(s): 升谷耕介, 尾本和也, 奥見雅由, 岡部安博, 北田秀久, 清水朋一, 石田英樹, 田邊一成, 鶴屋和彦, 北園孝成
  • Organizer: 第59回日本腎臓学会学術総会
  • Place of Presentation: 横浜市
  • Year and Date: 2016-06-17
• [Presentation] 糖尿病性腎症の治療戦略 -内科的管理を中心に- (2016)
  • Author(s): 升谷耕介
  • Organizer: 第59回日本腎臓学会学術総会
  • Place of Presentation: 横浜市
  • Year and Date: 2016-06-17
• [Presentation] ABO血液型不適合腎移植における 定期生検所見 (2016)
  • Author(s): 升谷耕介, 土本晃裕, 栗原啓, 岡部安博, 北田秀久, 中村雅史, 鶴屋和彦, 北園孝成
  • Organizer: 第59回日本腎臓学会学術総会
  • Place of Presentation: 横浜市
  • Year and Date: 2016-06-17
• [Presentation] Neutrophil-to-lymphocyte ratio as a predictor of Polyomavirus BK nephropathy in kidney transplant patients. (2016)
  • Author(s): Masutani K, Tsuchimoto A, Matsukuma Y, Kaku K, Kurihara K, Okabe Y, Tsuruya K, Nakamura M, Kitazono T
  • Organizer: American Transplant Congress 2016
  • Place of Presentation: Boston, MT, United States
  • Year and Date: 2016-06-11
  • Int'l Joint Research
• [Presentation] Histological analysis in ABO-compatible and incompatible kidney transplantation by performing 3-month and 1-year protocol biopsies. (2016)
  • Author(s): Masutani K, Tsuchimoto A, Matsukuma Y, Kurihara K, Okabe Y, Kitada H, Tanaka M, Tsuruya K, Kitazono T
  • Organizer: Transplantation Scientific Symposium Asian Regional Meeting 2016
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2016-04-08
  • Int'l Joint Research
• [Presentation] Viral infection after kidney transplantation: Current strategy for screening, diagnosis and treatment. (2016)
  • Author(s): Masutani K
  • Organizer: Kidney Transplant Asian Summit 2016
  • Place of Presentation: Osaka, Japan
  • Int'l Joint Research