BMC Nephrology | |
Validation of a newly proposed histopathological classification in Japanese patients with anti-neutrophil cytoplasmic antibody-associated glomerulonephritis | |
Yujiro Asada8  Kazuo Kitamura9  Takashi Wada3  Takeshi Tokura6  Shuichi Hisanaga7  Yoshiya Shimao1  Shigehiro Uezono1,10  Atsushi Yamashita8  Yunosuke Matsuura8  Junya Yamahana4  Kengo Furuichi2  Kiyoki Kitagawa2  Shouichi Fujimoto5  Takashi Iwakiri8  | |
[1] Department of Pathology, Miyazaki Prefectural Hospital, Miyazaki, Japan;Division of Blood Purification, Kanazawa University Hospital, Kanazawa, Japan;Division of Nephrology, Department of Laboratory Medicine, Kanazawa University, Kanazawa, Japan;Department of Internal Medicine, Toyama Prefectural Central Hospital, Toyama, Japan;Department of Hemovascular Medicine and Artificial Organs, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan;Department of Internal Medicine, Miyazaki Social Insurance Konan Hospital, Miyazaki, Japan;Department of Internal Medicine, Koga General Hospital, Miyazaki, Japan;Department of Pathology, University of Miyazaki, Miyazaki, Japan;Division of Circulation and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan;Department of Internal Medicine, Miyazaki Prefectural Hospital, Miyazaki, Japan | |
关键词: α-Smooth muscle actin; Immunohistochemistry; Histopathological classification; Anti-neutrophil cytoplasmic antibody; | |
Others : 1082914 DOI : 10.1186/1471-2369-14-125 |
|
received in 2012-07-23, accepted in 2013-06-12, 发布年份 2013 | |
【 摘 要 】
Background
A new histopathological classification of anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis was recently proposed. We evaluated the predictive value of this classification for renal outcome in Japanese patients.
Methods
We enrolled 122 patients with ANCA-associated glomerulonephritis diagnosed at several institutions in Japan between January 2000 and March 2010. Twenty patients were excluded because of observation durations of <1 year, and/or because their biopsy specimens contained <10 glomeruli. Renal biopsy specimens were categorized into four classes according to the proposed classification. We evaluated the predictive value of immunohistochemical staining for α-smooth muscle actin (SMA), Wilm’s tumor 1 (WT1), CD68, and cytokeratin for end-stage renal disease (ESRD).
Results
The study population included 54 men and 48 women. Age, estimated glomerular filtration rate (eGFR), and proteinuria were 66.3 ± 11.3 years, 21.6 ml/min. and 1.10 g/24 h, respectively. Eighty-six patients were positive for myeloperoxidase-ANCA, five were positive for proteinase 3-ANCA, and 11 were negative for both antibodies. Median follow-up time was 41.0 months. Twenty-three patients (22.5%) developed ESRD during the follow-up period. Twelve patients died during follow up; 7/12 patients developed ESRD before death, and 5/12 patients died without ESRD. The incidence of ESRD increased with sequential categories: focal, 2/46 (4.3%); crescentic, 9/32 (28%); mixed, 8/18 (44%); and sclerotic, 4/6 (67%). The focal class had the best renal survival and the sclerotic class had the worst renal survival (p < 0.001). Kaplan-Meier renal survival analysis was similar to that of the new classification system proposal. In the multivariate analysis, the classification system tended to be a prognostic factor for ESRD (p = 0.0686, crescentic, mixed and sclerotic vs. focal, hazard ratio (HR) [95% confidence interval, CI]; 2.99 [0.61–22.7], 5.04 [1.11–36.4] and 9.93 [1.53–85.7], respectively). α-SMA-positivity also tended to be associated with ESRD (p = 0.1074).
Conclusion
The new histopathological classification was associated with eGFR at 1 year and tended to be associated with ESRD in our Japanese cohort with ANCA-associated glomerulonephritis. α-SMA positivity might be an additional prognostic factor for ESRD.
【 授权许可】
2013 Iwakiri et al.; licensee BioMed Central Ltd.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
20141224190042414.pdf | 538KB | download | |
Figure 3. | 76KB | Image | download |
Figure 2. | 36KB | Image | download |
Figure 5. | 71KB | Image | download |
【 图 表 】
Figure 5.
Figure 2.
Figure 3.
【 参考文献 】
- [1]Pettersson EE, Sundelin B, Heigl Z: Incidence and outcome of pauci-immune necrotizing and crescentic glomerulonephritis in adults. Clin Nephrol 1995, 43:141-149.
- [2]Jennette JC, Falk RJ: Small-vessel vasculitis. N Engl J Med 1997, 337:1512-1523.
- [3]Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, Flores-Suarez LF, Gross WL, Guillevin L, Hagen EC, Hoffman GS, Jayne DR, Kallenberg CG, Lamprecht P, Langford CA, Luqmani RA, Mahr AD, Matteson EL, Merkel PA, Ozen S, Pusey CD, Rasmussen N, Rees AJ, Scott DG, Specks U, Stone JH, Takahashi K, Watts RA: 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum 2013, 65:1-11.
- [4]Bajema IM, Hagen EC, Hermans J, Noël LH, Waldherr R, Ferrario F, Van Der Woude FJ, Bruijn JA: Kidney biopsy as a predictor for renal outcome in ANCA-associated necrotizing glomerulonephritis. Kidney Int 1999, 56:1751-1758.
- [5]Hauer HA, Bajema IM, Van Houwelingen HC, Ferrario F, Noël LH, Waldherr R, Jayne DR, Rasmussen N, Bruijn JA, Hagen EC: Determinants of outcome in ANCA-associated glomerulonephritis: A prospective clinico-histopathological analysis of 96 patients. Kidney Int 2002, 62:1732-1742.
- [6]Neumann I, Kain R, Regele H, Soleiman A, Kandutsch S, Meisl FT: Histological and clinical predictors of early and late renal outcome in ANCA-associated vasculitis. Nephrol Dial Transplant 2005, 20:96-104.
- [7]Day CJ, Howie AJ, Nightingale P, Shabir S, Adu D, Savage CO, Hewins P: Prediction of ESRD in pauci-immune necrotizing glomerulonephritis: quantitative histomorphometric assessment and serum creatinine. Am J Kidney Dis 2010, 55:250-258.
- [8]de Lind van Wijngaarden RA, Hauer HA, Wolterbeek R, Jayne DR, Gaskin G, Rasmussen N, Noël LH, Ferrario F, Waldherr R, Hagen EC, Bruijn JA, Bajema IM: Clinical and histologic determinants of renal outcome in ANCA-associated vasculitis: A prospective analysis of 100 patients with severe renal involvement. J Am Soc Nephrol 2006, 17:2264-2274.
- [9]Berden AE, Ferrario F, Hagen EC, Jayne DR, Jennette JC, Joh K, Neumann I, Noël LH, Pusey CD, Waldherr R, Bruijn JA, Bajema IM: Histopathologic classification of ANCA-associated glomerulonephritis. J Am Soc Nephrol 2010, 21:1628-1636.
- [10]Fujimoto S, Uezono S, Hisanaga S, Fukudome K, Kobayashi S, Suzuki K, Hashimoto H, Nakao H, Nunoi H: Incidence of ANCA-related primary renal vasculitisin the Miyazaki Prefecture: the first population-based, retrospective, epidemiologic survey in Japan. Clin J Am Soc Nephrol 2006, 1:1016-1022.
- [11]Fujimoto S, Watts RA, Kobayashi S, Suzuki K, Jayne DR, Scott DG, Hashimoto H, Nunoi H: Comparison of the epidemiology of anti-neutrophil cytoplasmic antibody-associated vasculitis between Japan and the U.K. Rheumatology 2011, 50:1916-1920.
- [12]Watts R, Lane S, Hanslik T, Hauser T, Hellmich B, Koldingsnes W, Mahr A, Segelmark M, Cohen-Tervaert JW, Scott D: Development and validation of a consensus methodology for the classification of the ANCA-associated vasculitides and polyarteritis nodosa for epidemiological studies. Ann Rheum Dis 2007, 66:222-227.
- [13]Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, Yamagata K, Tomino Y, Yokoyama H, Hishida A: Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis 2009, 53:982-992.
- [14]Bajema IM, Hagen EC, Hansen BE, Hermans J, Noël LH, Waldherr R, Ferrario F, van der Woude FJ, Bruijn JA: The renal histopathology in systemic vasculitis: An international survey study of inter- and intra-observer agreement. Nephrol Dial Transplant 1996, 11:1989-1995.
- [15]Shigematsu H, Yamaguchi N, Koyama A: Glomerulointerstitial events in rapidly progressive nephritic syndrome, with special reference to histologic grade and stage on the renal lesions. Clin Exp Nephrol 1998, 2:330-338.
- [16]Andrassy K, Erb A, Koderisch J, Waldherr R, Ritz E: Wegener's granulomatosis with renal involvement: patient survival and correlations between initial renal function, renal histology, therapy and renal outcome. Clin Nephrol 1991, 35:139-147.
- [17]Gans RO, Kuizinga MC, Goldschmeding R, Assmann K, Huysmans FT, Gerlag PG, Donker AJ, Hoorntje SJ: Clinical features and outcome in patients with glomerulonephritis and antineutrophil cytoplasmic autoantibodies. Nephron 1993, 64:182-188.
- [18]Hogan SL, Nachman PH, Wilkman AS, Jennette JC, Falk RJ: Prognostic markers in patients with antineutrophil cytoplasmic autoantibody-associated microscopic polyangiitis and glomerulonephritis. J Am Soc Nephrol 1996, 7:23-32.
- [19]Franssen CF, Stegeman CA, Oost-Kort WW, Kallenberg CG, Limburg PC, Tiebosch A, De Jong PE, Tervaert JW: Determinants of renal outcome in anti-myeloperoxidase-associated necrotizing crescentic glomerulonephritis. J Am Soc Nephrol 1998, 9:1915-1923.
- [20]Hauer HA, Bajema IM, van Houwelingen HC, Ferrario F, Noël LH, Waldherr R, Jayne DR, Rasmussen N, Bruijn JA, Hagen EC, European Vasculitis Study Group (EUVAS): Renal histology in ANCA-associated vasculitis: differences between diagnostic and serologic subgroups. Kidney Int 2002, 61:80-89.
- [21]Lapraik C, Watts R, Bacon P, Carruthers D, Chakravarty K, D'Cruz D, Guillevin L, Harper L, Jayne D, Luqmani R, Mooney J, Scott D: BSR and BHPR guidelines for the management of adults with ANCA associated vasculitis. Rheumatology 2007, 46:1615-1616.
- [22]Yamagata K, Usui J, Saito C, Yamaguchi N, Hirayama K, Mase K, Kobayashi M, Koyama A, Sugiyama H, Nitta K, Wada T, Muso E, Arimura Y, Makino H, Matsuo S: ANCA-associated systemic vasculitis in Japan: clinical features and prognostic changes. Clin Exp Nephrol 2012, 16:580-588.
- [23]Uezono S, Sato Y, Hara S, Hisanaga S, Fukudome K, Fujimoto S, Nakao H, Kitamura K, Kobayashi S, Suzuki K, Hashimoto H, Nunoi H: Outcome of ANCA-associated primary renal vasculitis in Miyazaki prefecture. Intern Med 2007, 46:815-822.
- [24]Haas M, Eustace JA: Immune complex deposits in ANCA-associated crescentic glomerulonephritis: a study of 126 cases. Kidney Int 2004, 65:2145-2152.
- [25]Chen M, Xing GQ, Yu F, Liu G, Zhao MH: Complement deposition in renal histopathology of patients with ANCA-associated pauci-immune glomerulonephritis. Nephrol Dial Transplant 2009, 24:1247-1252.
- [26]Gigante A, Salviani C, Giannakakis K, Rosato E, Barbano B, Moroso A, Gasperini ML, Nofroni I, Salsano F, Cianci R, Pugliese F: Clinical and histological outcome predictors in renal limited pauci-immune crescentic glomerulonephritis: a single centre experience. Int J Immunopathol Pharmacol 2012, 25:287-292.
- [27]Bariety J, Hill GS, Mandet C, Irinopoulou T, Jacquot C, Meyrier A, Bruneval P: Glomerular epithelial-mesenchymal transdifferentiation in pauci-immune crescentic glomerulonephritis. Nephrol Dial Transplant 2003, 18:1777-1784.
- [28]Iehara N, Takeoka H, Tsuji H, Imabayashi T, Foster DN, Strauch AR, Yamada Y, Kita T, Doi T: Differentiation of smooth muscle phenotypes in mouse mesangial cells. Kidney Int 1996, 49:1330-1341.
- [29]Schnaper HW, Hayashida T, Hubchak SC, Poncelet AC: TGF-β signal transduction and mesangial cell fibrogenesis. Am J Physiol Renal Physiol 2003, 284:F243-F245.
- [30]Barnes JL, Gorin Y: Myofibroblast differentiation during fibrosis: role of NAD(P)H oxidases. Kidney Int 2011, 79:944-956.
- [31]Johnson RJ, Iida H, Alpers CE, Majesky MW, Schwartz SM, Pritzi P, Gordon K, Gown AM: Expression of smooth muscle cell phenotype by rat mesangial cells in immune complex nephritis. Alpha-smooth muscle actin is a marker of mesangial cell proliferation. J Clin Invest 1991, 87:847-858.
- [32]Desmouliere A, Darby IA, Gabbiani G: Normal and pathologic soft tissue remodeling: role of the myofibroblast, with special emphasis on liver and kidney fibrosis. Lab Invest 2003, 83:1689-1707.
- [33]Gabbiani G: The myofibroblast in wound healing and fibrocontractive diseases. J Pathol 2003, 200:500-503.
- [34]Kimura M, Asano M, Abe K, Miyazaki M, Suzuki T, Hishida A: Role of atrophic changes in proximal tubular cells in the peritubular deposition of type IV collagen in a rat renal ablation model. Nephrol Dial Transplant 2005, 20:1559-1565.