The study on the effect of tonsillectomy combined with steroid pulse therapy against IgA nephropathy

• Project/Area Number: 26460449
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Tohoku University
• Principal Investigator: Joh Kensuke 東北大学, 医学系研究科, 客員教授 (10057086)
• Co-Investigator(Kenkyū-buntansha): 中村 保宏 東北大学, 医学系研究科, 大学院非常勤講師 (80396499)
• Research Collaborator: Muto Masahiro 順天堂大学, 腎臓内科 ; Meng M 山形大学, 病理診断学講座
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: IgA腎症 / 寛解 / 扁桃摘出 / 扁桃炎 / 樹状細胞 / 腎生検 / 定量RTーPCR / T細胞 / B細胞 / 扁桃摘出術 / ステロイドパルス療法 / 治療効果 / 寛解予後 / ＩｇＡ腎症 / 糸球体腎炎 / フローサイトメトリー

Outline of Final Research Achievements

Tonsillectomy (TL) combined with steroid pulse therapy (SPT) has become a major choice against IgA nephropathy (IgAN) in Japan. The purpose was to figure out the factors preventing proteinuric remission（PUR）at 1 yr after the therapy and to contribute the indication of TL with SPT. PUR was found in 119 pts out of 194 pts (81%) at 1 year after. ROC analysis showed that cut off points, which were critical for a dichotomous classification of proteinuric remission, were 25% of interstitial fibrosis and 0.43 g/day of a grade of proteinuria, respectively. With these 2 parameters, PUR was predicted with 78% of probability.
Tonsil is an unique organ causing initial and progressive events to generate IgAN. Comparing the features of the IgAN tonsilitis with chronic tonsillitis, the number of T lymphocyte nodules with assembly of CD208-positive dendritic cells and the grade of lymphoepithelial involution correlated with frequency of crescent and segmental sclerosis in the kidney, respectively.

Research Products

• [Journal Article] Toll-Like Receptor 9 Stimulation Induces Aberrant Expression of a Proliferation-Inducing Ligand by Tonsillar Germinal Center B Cells in IgA Nephropathy. (2017)
  • Author(s): Muto M, Manfroi B, Suzuki H, Joh K, Nagai M, Wakai S, Righini C, Maiguma M, Izui S, Tomino Y, Huard B, Suzuki Y.
  • Journal Title: J Am Soc Nephrol Volume: 28 Issue: 4 Pages: 1227-1238
  • DOI: 10.1681/asn.2016050496
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Evidence from the Oxford Classification cohort supports the clinical value of subclassification of focal segmental glomerulosclerosis in IgA nephropathy. (2017)
  • Author(s): Bellur SS, Lepeytre F, Vorobyeva O, Troyanov S, Cook HT, Roberts IS, Alpers CE, Jennette JC, Joh K, et al.
  • Journal Title: Kidney Int Volume: 91 Issue: 1 Pages: 235-243
  • DOI: 10.1016/j.kint.2016.09.029
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Treatment of pediatric-onset lupus nephritis: a proposal of optimal therapy. (2017)
  • Author(s): Tanaka H, Joh K, Imaizumi T.
  • Journal Title: Clin Exp Nephrol Volume: - Issue: 5 Pages: 755-763
  • DOI: 10.1007/s10157-017-1381-1
  • Peer Reviewed / Open Access
• [Journal Article] Power Doppler Ultrasonography for Detection of Increased Vascularity in the Fascia:A Potential Early Diagnostic Tool in Fasciitis of Dermatomyositis. (2016)
  • Author(s): Yoshida K, Nishioka M, Matsushima S, Joh K, Oto Y, Yoshiga M, Otani K, Ito H, Hirai K, Furuya K, Ukichi T, Noda K, Kingetsu I, Kurosaka D.
  • Journal Title: Arthritis Rheumatol Volume: 68 Issue: 12 Pages: 2986-2991
  • DOI: 10.1002/art.39798
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Thymic stromal lymphopoietin in tonsillar follicular dendritic cells correlates (2016)
  • Author(s): Meng H, Li H, Ohe R, Naing YA, Yang S, Kabasawa T, Kato T, Osakabe M, Ohtake H, Ishida A, Lu J, Zhang L, Ohta N, Kakehata S, Joh K, Shi Q, Jin X, Geng J, Yamakawa M.
  • Journal Title: Transl Res Volume: 176 Pages: 1-17
  • DOI: 10.1016/j.trsl.2016.04.008
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Does Dent disease remain an underrecognized cause for young boys with focal glomerulosclerosis? (2016)
  • Author(s): Kubo K, Aizawa T, Watanabe S, Tsugawa K, Tsuruga K, Ito E, Joh K, Tanaka H.
  • Journal Title: Pediatr Int Volume: 58 Issue: 8 Pages: 747-749
  • DOI: 10.1111/ped.12944
  • Peer Reviewed / Open Access
• [Journal Article] Reproducibility for pathological prognostic parameters of the Oxford classification of IgA nephropathy: a Japanese cohort study of the Ministry of Health, Labor and Welfare (2016)
  • Author(s): Hisano S, Joh K, Katafuchi R, Shimizu A, Hashiguchi N, Kawamura T, Matsuo S
  • Journal Title: Clin Exp Nephrol Volume: 印刷中 Issue: 1 Pages: 92-96
  • DOI: 10.1007/s10157-016-1258-8
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Rapid specimen preparation to improve the throughput of electron microscopic volume imaging for three-dimensional analyses of subcellular ultrastructures with serial block-face scanning electron microscopy (2016)
  • Author(s): Thai TQ, Nguyen HB, Saitoh S, Wu B, Saitoh Y, Shimo S, Elewa YH, Ichii O, Kon Y, Takaki T, Joh K, Ohno N.
  • Journal Title: Med Mol Morphol Volume: Epub ahead of print Issue: 3 Pages: 1-9
  • DOI: 10.1007/s00795-016-0134-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Interferon-Dependent Transcript, Is Involved in a Negative Feedback Loop in Innate Immune Reactions in Human Mesangial Cells. (2016)
  • Author(s): Imaizumi T, Shimada T, Matsumiya T, Yoshida H, Watanabe S, Tsuruga K, Kawaguchi S, Murakami M, Joh K, Tanaka H.
  • Journal Title: Nephron Volume: 132 Issue: 2 Pages: 144-152
  • DOI: 10.1159/000443934
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A case of acute kidney injury caused by granulomatous tubulointerstitial nephritis associated with sarcoidosis and concomitant presence of anti-glomerular basement membrane antibody. (2016)
  • Author(s): Kamata Y, Azuma A, Hotta O, Joh K
  • Journal Title: Sarcoidosis Vasc Diffuse Lung Dis Volume: 32 Pages: 368-371
  • Peer Reviewed / Open Access
• [Journal Article] Interferon-Stimulated Gene 15, a Type I Interferon-Dependent Transcript, Is Involved in a Negative Feedback Loop in Innate Immune Reactions in Human Mesangial Cells (2016)
  • Author(s): Imaizumi T, Shimada T, Matsumiya T, Yoshida H, Watanabe S, Tsuruga K, Kawaguchi S, Murakami M, Joh K, Tanaka H
  • Journal Title: Nephron Volume: 132 Pages: 144-152
  • Peer Reviewed / Open Access
• [Journal Article] Rapid specimen preparation to improve the throughput of electron microscopic volume imaging for three-dimensional analyses of subcellular ultrastructures with serial block-face scanning electron microscopy (2016)
  • Author(s): Thai TQ, Nguyen HB, Saitoh S, Wu B, Saitoh Y, Shimo S, Elewa YH, Ichii O, Kon Y, Takaki T, Joh K, Ohno N
  • Journal Title: Med Mol Morphol Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Pathological sub-analysis of a multicenter randomized controlled trial of tonsillectomy combined with steroid pulse therapy versus steroid pulse monotherapy in patients with immunoglobulin A nephropathy (2015)
  • Author(s): Katafuchi R, Kawamura T, Joh K, Hashiguchi A, Hisano S, Shimizu A, Miyazaki Y, Nagata M, Matsuo S
  • Journal Title: Clin Exp Nephrol Volume: 20 Issue: 2 Pages: 244-252
  • DOI: 10.1007/s10157-015-1159-2
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Macrophage Infiltration into the Glomeruli in Lipoprotein Glomerulopathy (2015)
  • Author(s): Takasaki S, Maeda K, Joh K, Yamakage S, Fukase S, Takahashi T, Suzuki M, Matsunaga A, Saito T.
  • Journal Title: Case Rep Nephrol Dial Volume: 15 Issue: 3 Pages: 204-212
  • DOI: 10.1159/000441715
  • Peer Reviewed / Open Access
• [Journal Article] The Revisited Classification of GN in SLE at 10 Years: Time to Re-Evaluate Histopathologic Lesions (2015)
  • Author(s): Wilhelmus S, Alpers CE, Cook HT, Ferrario F, Fogo AB, Haas M, Joh K, Noël LH, Seshan SV, Bruijn JA, Bajema IM.
  • Journal Title: J Am Soc Nephrol Volume: 26 Issue: 12 Pages: 2938-2946
  • DOI: 10.1681/asn.2015040384
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Hypoelectrolytic isoosmotic solution for infusion prevents saline-induced ultrastuructural artifacts of renal biopsy specimens (2015)
  • Author(s): Nakamura Y, McNamara KM, Onodera S, Kitamoto Y, Kisu K, Shibahara Y, Kurosu A, Sasano H, Sato H, Joh K
  • Journal Title: Pathol Int Volume: 65 Issue: 7 Pages: 374-378
  • DOI: 10.1111/pin.12302
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Prominent hyperplasia of renin-producing juxtaglomerular apparatus after chronic and complete blockade of the renin-angiotensin system in adult IgA nephropathy (2015)
  • Author(s): Abe M, Joh K, Ieiri N, Hotta O, Utsunomiya Y, Sato H, Kisu K, Sakumo N, Kiyomoto H, Sato T, Taguma Y, Ito S
  • Journal Title: CEN Case Rep Volume: 4 Issue: 2 Pages: 228-232
  • DOI: 10.1007/s13730-015-0177-y
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] エビデンスに基づくIgA腎症診療ガイドライン2014 (2015)
  • Author(s): 松尾 清一, 木村 健二郎, 湯澤 由紀夫,漆原 真樹, 香美 祥二, 片渕 律子, 他
  • Journal Title: 日本腎臓学会誌 Volume: 57 Pages: 5-137
  • Acknowledgement Compliant
• [Journal Article] Severe intrinsic acute kidney injury associated with therapeutic dose of acetaminophen． (2015)
  • Author(s): Ito T，Watanabe S，Tsuruga K，Aizawa T，Hirono K，Joh K，Ito E，Tanaka H．
  • Journal Title: Pediatrics International Volume: 57 Issue: 2
  • DOI: 10.1111/ped.12607
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Latent prostate cancer in Japanese men who die unnatural deaths : A forensic autopsy study． (2015)
  • Author(s): Kido M，Hitosugi M，Ishii K，Kamimura S，Joh K．
  • Journal Title: Prostate Volume: in press Issue: 9 Pages: 917-922
  • DOI: 10.1002/pros.22975
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Validation of the Japanese histologic classification 2013 of immunoglobulin A nephropathy for prediction of long-term prognosis in a Japanese single-center cohort． (2014)
  • Author(s): Sato R，Joh K，Komatsuda A，Ohtani H，Okuyama S，Togashi M，Omokawa A，Nara M，Nagata D，Kusano E，Sawada K，Wakui H．
  • Journal Title: Clin Exp Nephrol Volume: - Issue: 3 Pages: 411-418
  • DOI: 10.1007/s10157-014-1004-z
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Toll-like receptor 3 signaling contributes to the expression of a neutrophil chemoattractant, CXCL1 in human mesangial cells (2014)
  • Author(s): Imaizumi T，Aizawa T，Segawa C，Shimada M，Tsuruga K，Kawaguchi S, Matsumiya T，Yoshida H, Joh K, Tanaka H.
  • Journal Title: Clinical and Experimental Nephrology Volume: Dec.4
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Renal patholology：SY23-2 a case of a new disease entity : Podocytic infolding glomerulopathy. (2014)
  • Author(s): Joh K
  • Journal Title: Pathology Volume: 46, Suppl 2 Pages: S41-S41
  • DOI: 10.1097/01.pat.0000454228.44878.31
  • Open Access / Acknowledgement Compliant
• [Journal Article] Renal epithelioid angiomyolipoma with malignant features：Histolgical evaluation and novel immunohistochemical findings. (2014)
  • Author(s): Konosu-Fukaya S，Nakamura Y，Fujishima F，Kasajima A，Keely M Mcnamara，Takahashi Y，Joh K，Saito H, Ioritani N, Ikeda Y, Arai Y, Watanabe M, Sasano H.
  • Journal Title: Pathology International Volume: 64 Issue: 3 Pages: 133-41
  • DOI: 10.1111/pin.12142
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Proposal of remission criteria for IgA nephropathy. (2014)
  • Author(s): Suzuki Y, Matsuzaki K, Suzuki H, Sakamoto N, Joh K, Kawamura T, Tomino Y, Matsuo S.
  • Journal Title: Clin Exp Nephrol Volume: 18 Issue: 3 Pages: 481-486
  • DOI: 10.1007/s10157-013-0849-x
  • NAID: 40019847882
  • Peer Reviewed / Open Access
• [Journal Article] Overestimation of the risk of progression to end-stage renal disease in the poor prognosis' group according to the 2002 Japanese histological classification for immunoglobulin A nephropathy. (2014)
  • Author(s): Miyazaki Y, Kawamura T, Joh K, Okonogi H, Koike K, Utsunomiya Y, Ogura M, Matsushima M, Yoshimura M, Horikoshi S, Suzuki Y, Furusu A, Yasuda T, Shirai S, Shibata T, Endoh M, Hattori M, Akioka Y, Katafuti R, Hashiguchi A, Kimura K, Matsuo S, Tomino Y.
  • Journal Title: Clin Exp Nephrol Volume: 18(3) Issue: 3 Pages: 475-80
  • DOI: 10.1007/s10157-013-0848-y
  • Peer Reviewed / Open Access
• [Journal Article] 原発性IgA腎症で生体腎移植を受けた27症例の摘出扁桃の検討 (2014)
  • Author(s): 星野慈恵，若井幸子，白川浩希，古宇田寛子，田邉一成，土谷 健，新田孝作，城 謙輔。
  • Journal Title: 日本臨床腎移植学会雑誌 Volume: 2 Pages: 184-9
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Potassium chloride in hypoelectrolytic isoosmotic solution for infusion prevents an artifact of electron microscopic morphology for fresh renal biopsy specimen (2016)
  • Author(s): Takaki T, Nakamura Y, Sato N, Joh K
  • Organizer: Kidney Week 2016
  • Place of Presentation: Chicago, USA.
  • Year and Date: 2016-11-15
  • Int'l Joint Research
• [Presentation] Pathology of lupus nephritis and antiphospholipid syndrome in renal biopsy. UPTODATE; Leiden Consensus Meeting (2016)
  • Author(s): Joh K
  • Organizer: 5th Heilongjiang International Forum on Renal Pathology and Kidney Research Progress
  • Place of Presentation: Harbin, China
  • Year and Date: 2016-08-05
  • Int'l Joint Research
• [Presentation] Histological Classification of IgA nephropathy; (2016)
  • Author(s): Joh K
  • Organizer: The 36th Annual Meeting of the Korean Society of Nephrology
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2016-06-02
  • Int'l Joint Research
• [Presentation] Classification of IgA Nephropathy May Produce a Score with a Broader Applicability Compared to the Split System of Oxford Classification (2015)
  • Author(s): Joh K, Hashiguchi A, Shimizu A, Katafuchi R, Kawamura T
  • Organizer: Kidney Week 2015
  • Place of Presentation: San Diego, USA
  • Year and Date: 2015-11-05
  • Int'l Joint Research
• [Presentation] A patient of POEMS syndrome with a special reference to the pathology of glomerular microangiopathy (2015)
  • Author(s): Joh K, Nakamura Y
  • Organizer: 4th Chinese-Japanese Renal Pathology Conference
  • Place of Presentation: Shanghai, China
  • Year and Date: 2015-09-26
  • Int'l Joint Research / Invited
• [Presentation] A Case Report of a 64-year-old Male with IgG1κ Monoclonal Deposition and Ultrastructural Striated Structure Mimicking Striated Muscle Bundle (2015)
  • Author(s): Tsukaguchi H, Joh K
  • Organizer: International Kidney and Monoclonal Gammopathy Research Group. 2nd International Meeting
  • Place of Presentation: La Rochelle, France
  • Year and Date: 2015-09-03
  • Int'l Joint Research
• [Presentation] Proposal for a Classification of the Glomerular Deposition Diseases (2015)
  • Author(s): Joh K
  • Organizer: International Kidney and Monoclonal Gammopathy Research Group. 2nd International Meeting
  • Place of Presentation: La Rochelle, France
  • Year and Date: 2015-09-03
  • Int'l Joint Research
• [Presentation] 脂質異常症と腎病変 (2015)
  • Author(s): 城 謙輔, 堀田 修
  • Organizer: 第５８回日本腎臓学会学術総会
  • Place of Presentation: 名古屋、名古屋国際会議場
  • Year and Date: 2015-06-05
  • Invited
• [Presentation] IgA腎症の病理学的鑑別診断と組織学的重症度分類の実際 (2015)
  • Author(s): 城 謙輔
  • Organizer: 第５８回日本腎臓学会学術総会
  • Place of Presentation: 名古屋、名古屋国際会議場
  • Year and Date: 2015-06-05
  • Invited
• [Presentation] 厚労省科研IgA腎症前向き研究をコホートとしたオックスフォード分類と日本分類の比較 (2015)
  • Author(s): 城 謙輔, 橋口 明典, 久野 敏, 清水 章
  • Organizer: 第１０４回日本病理学会総会
  • Place of Presentation: 名古屋、名古屋国際会議場
  • Year and Date: 2015-04-30
• [Presentation] ANCA associated glomerulonephritis in Japan: a comparative study on histological classification (2015)
  • Author(s): Joh K
  • Organizer: 2nd International Renal Pathology Conference
  • Place of Presentation: Tsukuba, Tsukuba International Congress Center
  • Year and Date: 2015-04-04
  • Int'l Joint Research / Invited
• [Presentation] Atypical Immunofluorescence Pattern in Adult Patients with X-Linked Alport Syndrome using Anti Type IV Collagen a1-a6 Antibodies (2014)
  • Author(s): Joh K, Miyasaka Y， Sado Y.
  • Organizer: Kidney Week
  • Place of Presentation: Philadelphia , USA
  • Year and Date: 2014-11-11 – 2014-11-16
• [Presentation] Comparison Between Nodular and Diffuse Lesion in Diabetic Glomerulopathy (2014)
  • Author(s): Joh K, Ishiyama K
  • Organizer: Kidney Week
  • Place of Presentation: Philadelphia , USA
  • Year and Date: 2014-11-11 – 2014-11-16
• [Presentation] SYMP 2: Kidney biopsy case seminar. Podocyte infolding disease． (2014)
  • Author(s): Joh K
  • Organizer: International Academy of Pathology Conference
  • Place of Presentation: Bangkok，Thailand
  • Year and Date: 2014-10-05 – 2014-10-10
• [Presentation] Pathology of ANCA-related nephropathy：clinicopathological correlation in the Japanese cohort． (2014)
  • Author(s): Joh K
  • Organizer: 3rd Heilongjiang International forum on renal pathology and kidney research progress
  • Place of Presentation: ハルピン，中国
  • Year and Date: 2014-08-09 – 2014-08-10
  • Invited
• [Presentation] Clinicopathological comparison between histological grade classification and Oxford Classification: Prospective study on 411 Japanese IgA nephropathy patients． (2014)
  • Author(s): Joh K．Hashiguchi A, Shimizu A, Hisano S, Katafuchi R, Kawamura T.
  • Organizer: 1st Oxford conference on IgA nephropathy
  • Place of Presentation: Oxford，UK
  • Year and Date: 2014-06-25 – 2014-06-27
• [Presentation] 腎生検診断における電顕のインパクト 糸球体の構成要素の形態・機能とその変容． (2014)
  • Author(s): 城 謙輔
  • Organizer: 第49回日本小児腎臓病理学会学術集会
  • Place of Presentation: 秋田ビューホテル、秋田
  • Year and Date: 2014-06-05 – 2014-06-07
  • Invited
• [Presentation] Renal histology and a grade of proteinuria predict proteinuric remission for the patients with tonsillectomy and steroid pulse therapy. (2014)
  • Author(s): Joh K．Nakamura Y, Kurosu A, Hotta O.
  • Organizer: The 14th Asian Pacific Congress of Nephrology
  • Place of Presentation: Shinagawa Prince Hotel, Tokyo, Japan
  • Year and Date: 2014-05-14 – 2014-05-17
• [Presentation] IgA腎症扁摘パルス療法後1年での寛解に関与する臨床病理学的因子の選択とその適応基準の開発 (2014)
  • Author(s): 城 謙輔、田中瑞子、谷内真司、中村保宏
  • Organizer: 第103回日本病理学総会
  • Place of Presentation: 広島国際会議場、広島
  • Year and Date: 2014-04-24 – 2014-04-27
• [Book] 腎生検電顕アトラス (2016)
  • Author(s): 城 謙輔
  • Publisher: 南山堂、東京
• [Book] Pathogenesis and Treatment in IgA Nephropathy. Ed. Tomino Y (2016)
  • Author(s): Joh K, MacNamara, KM
  • Publisher: Splinger, Japan
• [Book] 第６版 組織病理アトラス 小田義直、坂元亨宇、深山正久、松野吉宏、森永正二郎、森谷卓也編 (2015)
  • Author(s): 城謙輔
  • Publisher: 文光堂、東京
• [Book] Pathogenesis and Treatment in IgA Nephropathy. Ed. Tomino Y (2015)
  • Author(s): Kensuke Joh, Keely May McNamara
  • Publisher: Splinger