124 IgA 3 3 IgA IgA 16 IgA H-Grade25 %25 % 50 % 50 % 75 %75 % g C-Grade 0.5 g egfr 60 ml min 1.73 m 2 C-Grade 0.5 g egfr 60 ml min

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2011 53 2123 135. IgA IgA 3 IgA 3 IgA IgA 1995 IgA 2002 IgA 2 IgA IgA IgA IgA 3 Clinical guides for immunoglobulin A IgA nephropathy in Japan, third version

124 IgA 3 3 IgA IgA 16 IgA 5 287 1 2 4 H-Grade25 %25 % 50 % 50 % 75 %75 % 4 3 0.5 g C-Grade 0.5 g egfr 60 ml min 1.73 m 2 C-Grade 0.5 g egfr 60 ml min 1.73 m 2 C-Grade 3 4 4 IgA 7 IgA IgA 1 IgA 2 1968 J. Berger N. Hinglais IgA IgG 1970 30 % 20 % IgA chance proteinuria and or hematuria IgA 20 10 1993 20 20 38 %

125 3 IgA IgA C 3 IgA IgA1 J 2 IgA IgA 1 IgA 2 3 IgA EB 50 % IgA IgA IgA1 IgA mast cell IgA IgA 1995 2002 2002 IgA 2 1 IgA IgA 1 6 IgA 2 IgA * 1 2 3 5 20 4 5 4 7 IgA 4 16 IgA 2005 4 1 IgA 2 IgA 2 *

126 IgA 3 1 IgA 1 20 40 % 2 3 2 1 A B 2 C 3 A 3 B IgA 315 mg dl 4 A 4 B IgA C 1 2 A 2 B 3 B 3 2 1 5 6 HPF 2 3 IgA 350 mg dl IgA 4 IgA 3 IgA 4 * * IgA International IgA Nephropathy Network Renal Pathology Society 2009 IgA 8,9

127 * %OR split system 3 % AND lumped system 2 4 10 % 30 % AND %OR 10 IgA IgA 2 1 % 10 % 10025 % 25 50 % 50 % 11,12 2 8,9 11,12 * 2 IgA 2 7 8,9 50 % p 0.01 * IgA 3 1 A G 13 3 lumped system * 3 10 % 30 % OR split system 1 Cr 3 14 1995 7 Wakai 15

128 IgA 3 2IgA diffuse50 % focal50 % global 50 % segmental 50 % endocapillary hypercellularity karyorrhexis necrosis 2 GBM duplication increased mesangial matrix 2 2 sclerosis adhesion* segmental sclerosis global sclerosis collapsed ischemic glomerulus * extracapillary lesions extracapillary cellular proliferation or cellular crescent3 50 % % 10 % 10 25 % 26 50 %50 % extracapillary fibrocellular proliferation or fibrocellular crescent 50 % 90 %% 10 % 10 25 % 26 50 %50 % extracapillary fibrous proliferation or fibrous crescent90 % * 10 %% 10 25 % 26 50 %50 % mesangial hypercellularity normal 3 mild 4 5 moderate 6 7 severe 8 9 3 IgA cellular crescent fibrocellular crescent global sclerosis segmental sclerosis fibrous crescent 5 % 10,16

129 1 ABC D E FG 4 0 24.9 % A A C C 25 49.9 % A A C C 50 74.9 % A A C C 75 % A A C C A C 25 % 50 % 75 % H-Grade25 % H-Grade25 % 50 % H-Grade50 % 75 % H-Grade 75 % 4 acute lesion A chronic lesion C A A C C 4 12,17,18 IgA

130 IgA 3 9 Spearman s rank correlation R 0.741 p 0.001 10 4 IgA IgA 2 g 4 Jaffé egfr 100 HPF egfr 0.5 gegfr 60 ml min 1.73 m 2 0.5 g egfr 60 ml min 1.73 m 2 60 ml min 1.73 m 2 egfr 0.5 g 0.5 g 0.5 g egfr 60 ml min 1.73 m 2 60 ml min 1.73 m 2 5 5 g 0.5 0.5 egfr ml min 1.73 m 2 60 60 6 1 72 1.4 % OR 1 7 64 11 % OR 8.7 2 5 40 % OR 47.3 0 10 0 % OR 0 6 41 15 % OR 12.2 6 21 29 % OR 28.4 H-Grade 1 5 20 % OR 17.8 3 18 17 % OR 14.2 22 34 65 % OR 130 %OR vs H- Grade 0.5 g C-Grade 0.5 g egfr 60 ml min 1.73 m 2 C-Grade 0.5 g egfr 60 ml min 1.73 m 2 C-Grade 3 17,18 5 IgA H- GradeC-Grade 6 C-Grade H-Grade 72 1 1.4 % 15 15 50 50 4 7 IgA H- Grade C-Grade

131 7 IgA H-Grade 1 2 3 5 4 1 72 1 1.4 % 18.6 2 115 13 11.3 % 3.7 19.3 11.5 3 49 12 24.5 % 2.8 19.6 8.9 4 34 22 64.7 % 0.7 13.1 5.1 14 41.2 % 5 0 40 % 70 % RA 49 12 24.5 % 34 22 64.7 % 5 2 4.1 % 14 41.2 % 5 5.7 18 RA 68 48 13 % RA 87 78 40 % 69 90 47 % 79 88 65 % RA 4 RA J-KDR IgA Japan IgA nephropathy cohort study J-IGACS IgA IgA 1986 Kobayashi 19 20 25 23 20,21,24,25 IgA Hotta 26 27 28 IgA 29 30 31 fish oil 32

132 IgA 3 8 IgA IgA 1 23 4 CKD CKD CKD IgA 9 A 33 1 B egfr 1 34 C 25 35 kcal kg 35 33,34 1 A 33 3 6 1 34 B 36 0.8 1.0 g kg 36,37 C 2 3 2 A 35 1 3 1 B 0.8 1.0 g kg 36 6 g 36,37 C 2, 3 0.5 gegfr 60 ml min 1.73 m 2 9 3 A 35 1 1 38 B 0.6 0.8 g kg 36 6 g 36,37 35,36 C 2, 3 egfr 60 ml min 1.73 m 2 9 4 A 38 B 6 g 36,37 0.6 0.8 g kg 36 35,36 C 9 1 m 2 22kg 2 39,40 3 4 8 9

133 9 IgA IgA 1 0.5 g egfr 60 ml min 1.73 m 2 41,42 22 30 40 mg 2 41,42 1 20 mg RCT 23 egfr 60 ml min 1.73 m 2 41,43 2 1.5 mg dl 1.0 3.5 g 1 g 3 1 3 21,24 2 1.5 mg dl 44 3 26,28 1 3 3 2 3 29 1.5 2.0 mg dl 45 46 4 130 80 mmhg 1 g 125 75 mmhg 40 47 48 5 2 1.5 mg dl IgA 31 6 46 7 * 49 50 1 2 2008 IgA 0.5 g 3 3 111 53 7 3 21 60 3 IgA 10 50 11 IgA 3 CKD 50

134 IgA 3 IgA 10 3 IgA 3 11 1 Haas M. Histologic subclassification of IgA nephropathy a clinico pathologic study of 244 cases. Am J Kidney Dis 1997 29 829 842. 2 Lee KSM. Prognostic indicators of progressive renal disease in IgA nephropathy Emergence of a new histologic grading system. Am J Kidney Dis 1997 29 953 958. 3 Manno C, Strippoli GF, D Altri C, et al. A novel simpler histological classification for renal survival in IgA nephropathy a retrospective study. Am J Kidney Dis 2007 49 763 775. 4 Shigematsu H. Histological grading and staging of IgA nephropathy. Pathol Int 47 1997 194 202. 5 Lee HS, Lee MS, Lee SM, et al. Histological grading of IgA nephropathy predicting renal outcome revisiting H. S. Lee s glomerular grading system. Nephrol Dial Transplant 2005 20 342 348. 6 Katafuchi R, Kiyoshi Y, Oh Y et al. Glomerular score as a prognosticator in IgA nephropathy its usefulness and limitation. Clin Nephrol 1998 49 1 8. 7 Tomino Y, Sakai H, Special Study Group IgA Nephropathy on Progressive Glomerular Disease. Clinical guidelines for immunoglobulin A IgA nephropathy in Japan, second version. Clin Exp Nephrol 2003 7 93 97. 8 A Working Group of the International IgA Nephropathy Network and the Renal Pathology Society Cattran DC, Coppo R, Cook HT, et al. The Oxford classification of IgA nephropathy rationale, clinicopathological correlations, and classification. Kidney Int 2009 76 534 545. 9 A Working Group of the International IgA Nephropathy Network and the Renal Pathology Society Roberts ISD, Cook T, Troyanov S, et al. The Oxford classification of IgA Nephropathy Pathology definitions, correlations and reproducibility. Kidney Int 2009 76 546 556. 10IgA AND OR 18 2007 39 43 11IgA 2006 219 561 570 12IgA 2008 50 448 455 13IgA Annual Review 2010 2010 90 98 14IgA 18 2007 9 28 15 Wakai K, Kawamura T, Endoh M, et al. A scoring system to predict renal outcome in IgA nephropathy from a nationwide prospective study. Nephrol Dial Transplant 2006 21 2800 2808. 16IgA IgA 18 2007 29 38 17IgA 19 2008 9 32 18IgA Annual Review 2009 2009 87 94 19 Kobayashi Y, Fujii K, Hiki Y, et al. Steroid therapy in IgA nephropathy A prospective pilot study in moderate proteinuric cases. Q J Med 1986 61 935 943. 20 IgA 1991 33 761 768 21 Pozzi C, Bolasco P, Fogazzi G, et al. Corticosteroids in IgA nephropathy a randomized controlled trial. Lancet 1999 353 883 887. 22 Shoji T, Nakanishi I, Suzuki A, et al. Early treatment with corticosteroids ameliorates proteinuria, proliferative lesions, and mesangial phenotypic modulation in adult diffuse proliferative IgA nephropathy. Am J Kidney Dis 2000 35 194 201. 23 Katafuchi R, Ikeda K, Mizumasa T, et al. Controlled, prospective trial of steroid treatment in IgA nephropathy A limitation of low-dose prednisolone therapy. Am J Kidney Dis 2003 41 972 983. 24 Pozzi C, Andrulli S, Del Vecchio L, et al. Corticosteroid effectiveness in IgA nephropathy long-term results of a randomized, controlled trial. Am Soc Nephrol 2004 15 157 163. 25 Katafuchi R, Ninomiya T, Mizumasa T, et al. The improvement of renal survival with steroid pulse therapy in IgA nephropathy. Nephrol Dial Transplant 2008 23 3915 3920. 26 Hotta O, Miyazaki M, Furuta T, et al. Tonsillectomy and steroid pulse therapy significantly impact on clinical remission in patients with IgA nephropathy. Am J Kidney Dis 2001 38 736 743. 27 Xie Y, Nishi S, Ueno M, et al. The efficacy of tonsillectomy

135 on long-term renal survival in patients with IgA nephropathy. Kidney Int 2003 63 1861 1867. 28 Komatsu H, Fujimoto S, Hara S, et al. Effect of tonsillectomy plus steroid pulse therapy on clinical remission of IgA nephropathy a controlled study. Clin J Am Soc Nephrol 2008 3 1301 1307. 29IgA 21 2010 44 55 30 Yoshikawa N, Ito H, Sakai T, The Japanese Pediatric IgA Nephropathy Treatment Study Group. A controlled trial of combined therapy for newly diagnosed severe childhood IgA nephropathy. J Am Soc Nephrol 1999 10 101 109. 31 Ballardie FW, Roberts IS. Controlled prospective trial of prednisolone and cytotoxics in progressive IgA nephropathy. J Am Soc Nephrol 2002 13 142 148. 32 Donadio JV Jr, Bergstralh EJ, Offord KP, Spencer DC, Holley KE. A controlled trial of fish oil in IgA nephropathy. Mayo Nephrology Collaborative Group. N Engl J Med 1994 331 1194 1199. 33CKD CKD 2009 2009 30 39 34CKD CKD 2009 2009 54 57 35CKD 2009 2009 60 64 36 2007 2007 49 871 878 37CKD CKD 2009 2009 40 49 38 2007 21 25 39 CKD 2009 2009 65 68 40 2009 2009 53 58 41 Kobayashi Y, Hiki Y, Kokubo T, et al. Steroid therapy during the early stage of progressive IgA nephropathy. A 10 year follow-up study. Nephron 1996 72 237 242. 42 Tomino Y, Suzuki H, Horikoshi S, et al. Multicenter trial of adrenocorticosteroids in Japanese patients with IgA nephropathy results of the special study group IgA nephropathy on progressive glomerular disease, Ministry of Health, Labor and Welfare of Japan. Curr Top Steroid Res 2004 4 93 98. 43 Moriyama T, Honda K, Nitta K, et al. The effectiveness of steroid therapy for patients with advanced IgA nephropathy and impaired renal function. Clin Exp Nephrol 2004 8 237 242. 44 Tamura S, Ueki K, Ideura H, et al. Corticosteroid therapy in patients with IgA nephropathy and impaired renal function. Clin Nephrol 2001 55 192 195. 45 Sato M, Hotta O, Tomioka S, et al. Cohort study of advanced IgA nephropathy efficacy and limitations of corticosteroids with tonsillectomy. Nephron Clin Pract 2003 93 c137 145. 46IgA CKD 2009 2009 105 113 47 Russo D, Minutolo R, Pisani A, et al. Coadministration of losartan and enalapril exerts additive antiproteinuric effect in IgA nephropathy. Am J Kidey Dis 2001 38 18 25. 48 Tomino Y, Kawamura T, Kimura K, et al. Antiproteinuric effect of olmesartan in patients with IgA nephropathy. J Nephrol 2009 22 224 231. 49 Lee GSL, Choong HL, Chiang GSC, et al. Three-year randomized controlled trial of dipyridamole and low-dose warfarin in patients with IgA nephropathy and renal impairment. Nephrology 1997 3 117 121. 50 Ishii T, Kawamura T, Tsuboi N, et al. Prospective trial of combined therapy with heparin warfarin and renin-angiotensin system inhibitors in progressive IgA nephropathy. Contrib Nephrol 2007 157 114 119.