Development of disease specific therapy based on pathophysiology of IgA nephropathy focusing on microRNA

• Project/Area Number: 15K09695
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Wakayama Medical University
• Principal Investigator: Yoshikawa Norishige 和歌山県立医科大学, 医学部, 臨床研究センター長 (10158412)
• Co-Investigator(Kenkyū-buntansha): 中西 浩一 琉球大学, 医学(系)研究科(研究院), 教授 (50336880) ; 浜 武継 和歌山県立医科大学, 医学部, 助教 (00508020)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: IgA腎症 / microRNA

Outline of Final Research Achievements

The purpose of this study is to show the involvement and mechanism of microRNA (miRNA) in pathophysiology of IgA nephropathy. Micro RNA was extracted from a cryopreserved kidney biopsy specimen and microarray was performed. Two microRNAs were significantly decreased in the specimens of severe IgA nephropathy. In addition, one microRNA was significantly increased in severe IgA nephropathy specimens. Other microRNAs also showed a difference in severe IgA nephropathy and minimal changes. From the analysis of urine specimens, micro RNA may be used as a biomarker for noninvasively predicting prognosis.

Research Products

• [Journal Article] IgA nephropathy with presentation of nephrotic syndrome at onset in children. (2017)
  • Author(s): Shima Y, Nakanishi K, Sato M, Hama T, Mukaiyama H, Togawa H, Tanaka R, Nozu K, Sako M, Iijima K, Suzuki H, Yoshikawa N.
  • Journal Title: Pediatr Nephrol. Volume: 32(3) Issue: 3 Pages: 457-465
  • DOI: 10.1007/s00467-016-3502-6
  • Peer Reviewed
• [Journal Article] High incidence of idiopathic nephrotic syndrome in East Asian children: a nationwide survey in Japan (JP-SHINE study) (2017)
  • Author(s): Kikunaga K, Ishikura K, Terano C, Sato M, Komaki F, Hamasaki Y, Sasaki S, Iijima K, Yoshikawa N, Nakanishi K, Nakazato H, Matsuyama T, Ando T, Ito S, Honda M, On behalf of the Japanese Pediatric Survey Holding Information of Nephrotic syndrome (JP-SHINE) study of the Japanese Study Group of Renal Disease in Children
  • Journal Title: Clin Exp Nephrol Volume: in press Issue: 5 Pages: 889-894
  • DOI: 10.1007/s10157-016-1376-3
  • Peer Reviewed
• [Journal Article] Natural History and Genotype?Phenotype Correlation in Female X-Linked Alport Syndrome (2017)
  • Author(s): Yamamura Tomohiko、Nozu Kandai、Fu Xue Jun、Nozu Yoshimi、Ye Ming Juan、Shono Akemi、Yamanouchi Satoko、Minamikawa Shogo、Morisada Naoya、Nakanishi Koichi、Shima Yuko、Yoshikawa Norishige、Ninchoji Takeshi、Morioka Ichiro、Kaito Hiroshi、Iijima Kazumoto
  • Journal Title: Kidney Int Rep. Volume: 2 Issue: 5 Pages: 850-855
  • DOI: 10.1016/j.ekir.2017.04.011
  • NAID: 120006373817
  • Peer Reviewed / Open Access
• [Journal Article] Aberrant Smad3 phosphoisoforms in cyst-lining epithelial cells in the cpk mouse, a model of autosomal recessive polycystic kidney disease (2017)
  • Author(s): Hama Taketsugu、Nakanishi Koichi、Sato Masashi、Mukaiyama Hironobu、Togawa Hiroko、Shima Yuko、Miyajima Masayasu、Nozu Kandai、Nagao Shizuko、Takahashi Hisahide、Sako Mayumi、Iijima Kazumoto、Yoshikawa Norishige、Suzuki Hiroyuki
  • Journal Title: American Journal of Physiology-Renal Physiology Volume: 313 Issue: 6 Pages: F1223-F1231
  • DOI: 10.1152/ajprenal.00697.2016
  • Peer Reviewed
• [Journal Article] Crescentic IgA nephropathy in a child: Effect of a new combination therapy (2017)
  • Author(s): Okamoto M, Yokoyama N, Nozu K, Nakanishi K, Yoshikawa N
  • Journal Title: Pediatr Int Volume: 59 Issue: 4 Pages: 501-503
  • DOI: 10.1111/ped.13225
  • Peer Reviewed
• [Journal Article] Congenital nephrotic syndrome with a novel NPHS1 mutation (2016)
  • Author(s): Yoshizawa C, Kobayashi Y, Ikeuchi Y, Tashiro M, Kakegawa S, Watanabe T, Goto Y, Nakanishi K, Yoshikawa N, Arakawa H
  • Journal Title: Pediatr Int Volume: 58 Issue: 4 Pages: 1211-1215
  • DOI: 10.1007/s10157-016-1319-z
  • Peer Reviewed
• [Journal Article] Somatic mosaicism and variant frequency detected by next-generation sequencing in X-linked Alport syndrome. (2016)
  • Author(s): Fu XJ, Nozu K, Kaito H, Ninchoji T, Morisada N, Nakanishi K, Yoshikawa N, Ohtsubo H, Matsunoshita N, Kamiyoshi N, Matsumura C, Takagi N, Maekawa K, Taniguchi-Ikeda M, Iijima K
  • Journal Title: Eur J Hum Genet Volume: 24 Issue: 3 Pages: 387-391
  • DOI: 10.1038/ejhg.2015.113
  • Peer Reviewed
• [Journal Article] Differential diagnosis of Bartter syndrome, Gitelman syndrome, and pseudo-Bartter/Gitelman syndrome based on clinical characteristics (2016)
  • Author(s): Matsunoshita N, Nozu K, Shono A, Nozu Y, Fu XJ, Morisada N, Kamiyoshi N, Ohtsubo H, Ninchoji T, Minamikawa S, Yamamura T, Nakanishi K, Yoshikawa N, Shima Y, Kaito H, Iijima K
  • Journal Title: Genetics in Medicine Volume: 18 Issue: 2 Pages: 180-188
  • DOI: 10.1038/gim.2015.56
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Clinical manifestations of Henoch-Schoenlein purpura nephritis and IgA nephropathy: comparative analysis of data from the Japan Renal Biopsy Registry (J-RBR) (2016)
  • Author(s): Komatsu H, Fujimoto S, Yoshikawa N, Kitamura H, Sugiyama H, Yokoyama H
  • Journal Title: Clin Exp Nephrol Volume: 20 Issue: 4 Pages: 552-60
  • DOI: 10.1007/s10157-015-1177-0
  • Peer Reviewed
• [Journal Article] Genetic, Clinical, and Pathologic Backgrounds of Patients with Autosomal Dominant Alport Syndrome. (2016)
  • Author(s): Kamiyoshi N, Nozu K, Fu XJ, Morisada N, Nozu Y, Ye MJ, Imafuku A, Miura K, Yamamura T, Minamikawa S, Shono A, Ninchoji T, Morioka I, Nakanishi K, Yoshikawa N, Kaito H, Iijima K
  • Journal Title: Clin J Am Soc Nephrol. Volume: 11 Issue: 8 Pages: 1441-1449
  • DOI: 10.2215/cjn.01000116
  • Peer Reviewed
• [Journal Article] Long-term outcome of childhood IgA nephropathy with minimal proteinuria. (2015)
  • Author(s): Higa A, Shima Y, Hama T, Sato M, Mukaiyama H, Togawa H, Tanaka R, Nozu K, Sako M, Iijima K, Nakanishi K, Yoshikawa N.
  • Journal Title: Pediatr Nephrol. Volume: 30(12) Issue: 12 Pages: 2121-7
  • DOI: 10.1007/s00467-015-3176-5
  • Peer Reviewed
• [Journal Article] Risk factors for persistent proteinuria after a 2-year combination therapy for severe childhood IgA nephropathy (2015)
  • Author(s): Kamei K, Nakanishi K, Ito S, Ishikura K, Hataya H, Honda M, Nozu K, Iijima K, Shima Y, Yoshikawa N
  • Journal Title: Pediatr Nephrol Volume: 30 Issue: 6 Pages: 961-967
  • DOI: 10.1007/s00467-014-3019-9
  • Peer Reviewed
• [Journal Article] Morbidity in children with frequently relapsing nephrosis:10-year follow-up of a randomized controlled trial (2015)
  • Author(s): Ishikura K, Yoshikawa N, Nakazato H, Sasaki S, Nakanishi K, Matsuyama T, Ito S, Hamasaki Y, Yata N, Ando T, Iijima K, Honda M
  • Journal Title: Pediatr Nephrol Volume: 30 Issue: 3 Pages: 459-468
  • DOI: 10.1007/s00467-014-2955-8
  • Peer Reviewed
• [Journal Article] Renal biopsy criterion in idiopathic nephrotic syndrome with microscopic hematuria at onset (2015)
  • Author(s): Hama T, Nakanishi K, Shima Y, Sato M, Mukaiyama H, Togawa H, Hamahira K, Tanaka R, Kaito H, Nozu K, Iijima K, Yoshikawa N
  • Journal Title: Pediatr Nephrol Volume: 30 Issue: 3 Pages: 445-450
  • DOI: 10.1007/s00467-014-2946-9
  • Peer Reviewed
• [Journal Article] A multicenter randomized trial indicates initial prednisolone treatment for childhood nephrotic syndrome for two months is not inferior to six-month treatment (2015)
  • Author(s): Yoshikawa N, Nakanishi K, Sako M, Oba MS, Mori R, Ota E, Ishikura K, Hataya H, Honda M, Ito S, Shima Y, Kaito H, Nozu K, Nakamura H, Igarashi T, Ohashi Y, Iijima K
  • Journal Title: Kidney Int Volume: 87 Issue: 1 Pages: 225-232
  • DOI: 10.1038/ki.2014.260
  • Peer Reviewed / Open Access
• [Journal Article] Biopsy timing and Oxford classification variables in childhood/adolescent IgA nephropathy. (2015)
  • Author(s): Shima Y, Nakanishi K, Hama T, Sato M, Mukaiyama H, Togawa H, Tanaka R, Kaito H, Nozu K, Iijima K, Yoshikawa N.
  • Journal Title: Pediatric Nephrollogy Volume: 30(2) Issue: 2 Pages: 293-9
  • DOI: 10.1007/s00467-014-2862-z
  • Peer Reviewed
• [Journal Article] 私の処方 IgA腎症・紫斑病性腎炎 (2015)
  • Author(s): 中西浩一、吉川徳茂
  • Journal Title: 小児科臨床 Volume: 68 Pages: 809-815
• [Journal Article] 小児期発症のADPKDとARPKD (2015)
  • Author(s): 中西浩一、吉川徳茂
  • Journal Title: 腎臓内科・泌尿器科 Volume: 1 Pages: 212-218
  • NAID: 40022582482
• [Presentation] A variety of phenotypes reflected by genotypes and laminin β2 sxpression on glomerulus in Pierson syndrome (2017)
  • Author(s): Minamikawa S, Nozu K, Fujimura J, Nakanishi K, Horinouchi T, Yamamura T, Ninchoji T, Kaito H, Yoshikawa N, Iijima K
  • Organizer: 50th Anniversary Meeting of the European Society for Pediatric Nephrology
  • Int'l Joint Research
• [Presentation] In vitro splicing assays to detecy intronic pathogenic variants in inherited kidney disease (2017)
  • Author(s): Nakanishi K, Nozu K, Fujimura J, Horinouchi T, Minamikawa S, Yamamura T, Ninchoji T, Kaito H, Yoshikawa N, Iijima K
  • Organizer: 50th Anniversary Meeting of the European Society for Pediatric Nephrology
  • Int'l Joint Research
• [Presentation] New combination therapy with prednisolone (PSL), mizoribine and lisinopril for severe childhood IgA Nephropathy (IgAN) (2017)
  • Author(s): Norishige Yoshikawa, Yuko Shima, Masashi Sato, Taketsugu Hama, Hironobu Mukaiyam, Hiroko Togawa, Hiroyuki Suzuki, Hiroshi Kaito, Kandai Nozu, Kazumoto Iijima, Koichi Nakanishi
  • Organizer: 50th Anniversary Meeting of the European Society for Pediatric Nephrology
  • Int'l Joint Research
• [Presentation] Foctors related to proteinuria relapse in childhood IgA Nephropathy (2017)
  • Author(s): Yuko Shima, Koichi Nakanishi, Masashi Sato, Taketsugu Hama, Yu Tanaka, Hironobu Mukaiyama, Hiroko Togawa, Hiroshi Kaito, Kandai Nozu, Ryojiro Tanaka, Kazumoto Iijima, Hiroyuki Suzuki, Norishige Yoshikawa
  • Organizer: 50th Annual Meeting of the American Society of Nephrology
  • Int'l Joint Research
• [Presentation] Differential expressions of miR-378a-3p/ADAMTS1 in cpk mice, a model of ARPKD (2016)
  • Author(s): Sato M, Koichi Nakanishi K, Hama T, Mukaiyama H, Togawa H, Yuko Shima1, Miyajima M, Nozu K, Nagao S, Takahashi H, Iijima K Yoshikawa N, Suzuki H
  • Organizer: 49th Annual Meeting of the American Society of Nephrology
  • Place of Presentation: Chicago, USA
  • Year and Date: 2016-11-15
  • Int'l Joint Research
• [Presentation] Childhood IgA nephropathy presenting acute nephritic syndrome at onset (2016)
  • Author(s): Shima Y, Nakanishi K, Hama T, Sato M, Mukaiyama H, Togawa H, Kaito H, Nozu K, Tanaka R, Iijima K, Suzuki H, Yoshikawa N
  • Organizer: 49th Annual Meeting of the American Society of Nephrology
  • Place of Presentation: Chicago, USA
  • Year and Date: 2016-11-15
  • Int'l Joint Research
• [Presentation] Therapeutic options for IgA Nephropathy (2016)
  • Author(s): Yoshikawa N
  • Organizer: 17th International Pediatric Nephrology Association
  • Place of Presentation: Iguac, Brazil
  • Year and Date: 2016-09-20
  • Int'l Joint Research / Invited
• [Presentation] Genetic and clinical characteristics of female X-linked Alport syndrome : 267 cases study (2016)
  • Author(s): Yamamura Y, Nozu K, Nakanishi K, Horinouchi T, Fujimura J, Minamikawa S, Kamiyoshi N, Ninchoji T, Kaito H, Morisada N, Nakanishi K, Yoshikawa N, Iijima K
  • Organizer: 17th International Pediatric Nephrology Association
  • Place of Presentation: Iguac, Brazil
  • Year and Date: 2016-09-20
  • Int'l Joint Research
• [Presentation] Genetic approach to the siblings with congenital / infantile nephrotic syndrome by targeted resequence (2016)
  • Author(s): Minamikawa S, Nozu K, Nakanishi K, Yamamura T, Ninchoji T, Nakanishi K, Yoshikawa N, Iijima K
  • Organizer: 17th International Pediatric Nephrology Association
  • Place of Presentation: Iguac, Brazil
  • Year and Date: 2016-09-20
  • Int'l Joint Research
• [Presentation] Clinical characteristics and long term outcome of diarrhea associated hemolytic uremic syndrome (2016)
  • Author(s): Nakanishi K, Ninchoji T, Horinouchi T, Fujimura J, Yamamura T, Minamikawa S, Nozu K, Nakanishi K, Yoshikawa N, Iijima K
  • Organizer: 17th International Pediatric Nephrology Association
  • Place of Presentation: Iguac, Brazil
  • Year and Date: 2016-09-20
  • Int'l Joint Research
• [Presentation] Crescentic IgA nephropathy in children (2016)
  • Author(s): Shima Y, Nakanishi K, Sato M, Nozu K, Tanaka R, Iijima K, Suzuki H, Yoshikawa N
  • Organizer: 17th International Pediatric Nephrology Association
  • Place of Presentation: Iguac, Brazil
  • Year and Date: 2016-09-20
  • Int'l Joint Research
• [Presentation] Immunoglobulin A nephropathy showing acute kidney injury and severe endocapillary proliferation (2016)
  • Author(s): Hashimura Y, Enomoto M, Onishi Y, Okizuka Y, Hayashi S, Uchiyama N, Yoshikawa N, Minami H
  • Organizer: 17th International Pediatric Nephrology Association
  • Place of Presentation: Iguac, Brazil
  • Year and Date: 2016-09-20
  • Int'l Joint Research
• [Presentation] Childhood IgA nephropathy with nephrotic syndrome (NS-IgAN) at onset (2015)
  • Author(s): Shima Y, Nakanishi K, Hama T, Sato M, Togawa H, Mukaiyama H, Kaito H, Nozu K, Tanaka R, Iijima K, Yoshikawa N
  • Organizer: 48th Annual Meeting of the American Society of Nephrology
  • Place of Presentation: San Diego, USA
  • Year and Date: 2015-11-05
  • Int'l Joint Research
• [Presentation] Somatic mosaicism and variant frequency detected by next-generation sequencing in X-linked Alport syndrome (2015)
  • Author(s): Kamiyoshi N, Nozu K, Yamamura T, Ninchoji T, Shima Y, Nakanishi K, Yoshikawa N, Iijima K
  • Organizer: 48th Annual Meeting of the American Society of Nephrology
  • Place of Presentation: San Diego, USA
  • Year and Date: 2015-11-05
  • Int'l Joint Research
• [Presentation] Dysregulation of miR-378a-3p and ADAMTS1 gene in cpk mice, a model of ARPKD (2015)
  • Author(s): Sato M, Nakanishi K, Hama T, Mukaiyama H, Togawa H, Shima Y, Miyajima M, Nozu K, Nagao S, Takahashi H, Iijima K, Yoshikawa N
  • Organizer: 48th Annual Meeting of the American Society of Nephrology
  • Place of Presentation: San Diego, USA
  • Year and Date: 2015-11-05
  • Int'l Joint Research
• [Presentation] Genetic, pathological and clinical backgrounds in autosomal dominant Alport syndrome (2015)
  • Author(s): Nozu K, Kamiyoshi N, Minamikawa S, Matsunoshita N, Otsubo H, Yamamura T, Ninchoji T, Nakanishi K, Yoshikawa N, Iijima K
  • Organizer: 48th annual scientific meeting of the European Society for Pediatric Nephrology
  • Place of Presentation: Brussels, Belgium
  • Year and Date: 2015-09-03
  • Int'l Joint Research
• [Presentation] IgA腎症発症関連分子の腎における発現 (2015)
  • Author(s): 佐藤匡，島友子，浜武継，向山弘展，戸川寛子，中西浩一，吉川徳茂
  • Organizer: 第58回日本腎臓学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-06-05
• [Presentation] 発症時ネフローゼ症候群を呈する小児IgA腎症（NS-IｇAN）の検討 (2015)
  • Author(s): 島友子，中西浩一，濱武継，佐藤匡，向山弘展，戸川寛子，貝藤裕史，野津寛大，田中亮二郎，飯島一誠，吉川徳茂
  • Organizer: 日本小児腎臓病学会学術集会第50回記念大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-06-05
• [Presentation] Evidence-based Treatments for Childhood IgA Nephropathy (2015)
  • Author(s): Nakanishi K, Yoshikawa N
  • Organizer: The 11th Asian Society for Pediatric Research
  • Place of Presentation: Osaka
  • Year and Date: 2015-04-15
  • Int'l Joint Research / Invited
• [Book] Pediatric Nephrology 7th edition (2016)
  • Author(s): Nakanishi K, Yoshikawa N
  • Total Pages: 2730
  • Publisher: Springer
• [Book] Pediatric Nephrology 7th ed. (2015)
  • Author(s): Nakanishi K, Yoshikawa N
  • Total Pages: 2730
  • Publisher: Springer, Heidelberg
• [Book] 疾患からみる画像診断の進め方・読み方（小児科診療増刊号） (2015)
  • Author(s): 中西浩一、吉川徳茂
  • Total Pages: 348
  • Publisher: 診断と治療社