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Pathological spectrums and renal prognosis of severe lupus patients with rapidly progressive glomerulonephritis

  • Original Article - Observational Research
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Abstract

The objectives of the study were to investigate the pathological features and renal prognosis of severe lupus patients with rapidly progressive glomerulonephritis. One hundred and one cases of biopsy-proven severe LN with rapidly progressive glomerulonephritis (RPGN) were analyzed in this retrospective study. Another 200 severe LN patients without RPGN were randomly enrolled as a control group. Their clinicopathological data and long-term outcome were compared. There were 76 females and 25 males with an average age of 31.9 ± 14.2 years followed for a median period of 4 years. Compared with controls, patients with RPGN had shorter LN duration (p = 0.008), higher level of creatinine (p < 0.001), severe anemia (p = 0.037), heavier hematuria (p < 0.001), severe tubular injury parameters [NAG (p < 0.001), RBP (p < 0.001), C3 (p < 0.001)], higher scores of AI (p = 0.001) and CI (p = 0.004), higher proportions of glomerular sclerosis (0.033) and crescents (p < 0.001), severe tubulointerstitial lesions (p < 0.001) and interstitial inflammation (p < 0.001), lower rate of complete remission (33.9 vs 68.2 %) and higher rate of treatment failure (46.8 vs 7.9 %). The 3-, 5- and 10-year cumulative renal survival rates of RPGN and non-RPGN patients were 65.1 versus 53.9 versus 42.9 and 96.9 versus 94.9 versus 91.7 %, respectively. Multivariate analysis revealed that SCr concentration and the proportion of crescents were the most important risk factors for end-stage renal disease (ESRD) in severe LN with RPGN (p < 0.001). In conclusion, RPGN occurred in 3.6 % of LN and is associated with severe renal manifestations, serious sclerotic and crescentic glomeruli lesions, severe tubulointerstitial inflammation, atrophy and fibrosis, prominent leukocyte infiltration and worse treatment response. Multivariate analysis revealed that SCr concentration and the proportion of crescents were the most important risk factors for ESRD. 57.1 % of severe LN patients with RPGN might progress to ESRD within 10 years.

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References

  1. Sumethkul V, Chalermsanyakorn P, Changsirikulchai S, Radinahamed P (2000) Lupus nephritis: a challenging cause of rapidly progressive crescentic glomerulonephritis. Lupus 9:424–428

    Article  CAS  PubMed  Google Scholar 

  2. Masani NN, Imbriano LJ, D’Agati VD, Markowitz GS (2005) Sle and rapidly progressive glomerulonephritis. Am J Kidney Dis 45:950–955

    Article  PubMed  Google Scholar 

  3. Jennette JC (2003) Rapidly progressive crescentic glomerulonephritis. Kidney Int 63:1164–1177

    Article  PubMed  Google Scholar 

  4. Glassock R (1978) A clinical and immunopathologic dissection of rapidly progressive glomerulonephritis. Nephron 22:253–264

    Article  CAS  PubMed  Google Scholar 

  5. Yeung C, Wong K, Wong W, Ng M, Chan K, Ng W (1984) Crescentic lupus glomerulonephritis. Clin Nephrol 21:251–258

    CAS  PubMed  Google Scholar 

  6. Andrassy K, Küster S, Waldherr R, Ritz E (1991) Rapidly progressive glomerulonephritis: analysis of prevalence and clinical course. Nephron 59:206–212

    Article  CAS  PubMed  Google Scholar 

  7. Niaudet P (2000) Treatment of lupus nephritis in children. Pediatr Nephrol 14:158–166

    Article  CAS  PubMed  Google Scholar 

  8. Bogdanović R, Nikolić V, Pašić S, Dimitrijević J, Lipkovska-Marković J, Erić-Marinković J, Ognjanović M, Minić A, Stajić N (2004) Lupus nephritis in childhood: a review of 53 patients followed at a single center. Pediatr Nephrol 19:36–44

    Article  PubMed  Google Scholar 

  9. Weening JJ, D D’AGATI V, Schwartz MM, Seshan SV, Alpers CE, Appel GB, Balow JE, Bruijn JA, Cook T, Ferrario F (2004) The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int 65:521–530

    Article  PubMed  Google Scholar 

  10. Mosca M, Pasquariello A, Tavoni A, Moriconi L, Moneta I, Innocenti M, Bencivelli W, Bombardieri S (1997) Predictors of renal outcome in diffuse proliferative glomerulonephritis in systemic lupus erythematosus. Lupus 6:371–378

    Article  CAS  PubMed  Google Scholar 

  11. Sumboonnanonda A, Vongjirad A, Suntornpoch V, Laohapand T, Parichatikanond P (1998) Renal pathology and long-term outcome in childhood sle. J Med Assoc Thail 81:830–834

    CAS  Google Scholar 

  12. Huong D, Papo T, Beaufils H, Wechsler B, Bletry O, Baumelou A, Godeau P, Piette J (1999) Renal involvement in systemic lupus erythematosus. A study of 180 patients from a single center. Medicine 78:148–166

    Article  CAS  PubMed  Google Scholar 

  13. Wang L-C, Yang Y-H, Lu M-Y, Chiang B-L (2003) Retrospective analysis of mortality and morbidity of pediatric systemic lupus erythematosus in the past two decades. J Microbiol Immunol Infect 36:203–208

    PubMed  Google Scholar 

  14. Hochberg MC (1997) Updating the american college of rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40:1725

    Article  CAS  PubMed  Google Scholar 

  15. Lewis EJ, Hunsicker LG, Lan S-P, Rohde RD, Lachin JM (1992) A controlled trial of plasmapheresis therapy in severe lupus nephritis. N Engl J Med 326:1373–1379

    Article  CAS  PubMed  Google Scholar 

  16. Chen YE, Korbet SM, Katz RS, Schwartz MM, Lewis EJ (2008) Value of a complete or partial remission in severe lupus nephritis. Clin J Am Soc Nephrol 3:46–53

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Katz SM (1982) Renal disease: classification and atlas of glomerular diseases. JAMA 248(16):2053–2054

    Article  Google Scholar 

  18. Austin H, Muenz LR, Joyce KM, Antonovych TT, Balow JE (1984) Diffuse proliferative lupus nephritis: identification of specific pathologic features affecting renal outcome. Kidney Int 25:689–695

    Article  PubMed  Google Scholar 

  19. Solez K, Axelsen R, Benediktsson H, Burdick JF, Cohen AH, Colvin RB, Croke BP, Droz D, Dunnill MS, Halloran PF (1993) International standardization of criteria for the histologic diagnosis of renal allograft rejection: the banff working classification of kidney transplant pathology. Kidney Int 44:411

    Article  CAS  PubMed  Google Scholar 

  20. Hsieh C, Chang A, Brandt D, Guttikonda R, Utset TO, Clark MR (2011) Predicting outcomes of lupus nephritis with tubulointerstitial inflammation and scarring. Arthritis Care Res 63:865–874

    Article  Google Scholar 

  21. Banfi G, Bertani T, Boeri V, Faraggiana T, Mazzucco G, Monga G, Sacchi G (1991) Renal vascular lesions as a marker of poor prognosis in patients with lupus nephritis. Am J Kidney Dis 18:240–248

    Article  CAS  PubMed  Google Scholar 

  22. Appel G, Pirani C, D’Agati V (1994) Renal vascular complications of systemic lupus erythematosus. J Am Soc Nephrol 4:1499–1515

    CAS  PubMed  Google Scholar 

  23. Descombes E, Droz D, Drouet L, Grünfeld J-P, Lesavre P (1997) Renal vascular lesions in lupus nephritis. Medicine 76:355–368

    Article  CAS  PubMed  Google Scholar 

  24. Schwartz M (1992) Lupus vasculitis. Contrib Nephrol 99:35

    CAS  PubMed  Google Scholar 

  25. Illei GG, Austin HA, Crane M, Collins L, Gourley MF, Yarboro CH, Vaughan EM, Kuroiwa T, Danning CL, Steinberg AD (2001) Combination therapy with pulse cyclophosphamide plus pulse methylprednisolone improves long-term renal outcome without adding toxicity in patients with lupus nephritis. Ann Int Med 135:248–257

    Article  CAS  PubMed  Google Scholar 

  26. Chan T, Tse K, Tang CS, Lai K, Li F (2005) Long-term outcome of patients with diffuse proliferative lupus nephritis treated with prednisolone and oral cyclophosphamide followed by azathioprine. Lupus 14:265–272

    Article  CAS  PubMed  Google Scholar 

  27. Korbet SM, Lewis EJ, Schwartz MM, Reichlin M, Evans J, Rohde RD (2000) Factors predictive of outcome in severe lupus nephritis. Am J Kidney Dis 35:904–914

    Article  CAS  PubMed  Google Scholar 

  28. Mok CC, Ho CTK, Chan KW, Lau CS, Wong RWS (2002) Outcome and prognostic indicators of diffuse proliferative lupus glomerulonephritis treated with sequential oral cyclophosphamide and azathioprine. Arthritis Rheum 46:1003–1013

    Article  CAS  PubMed  Google Scholar 

  29. Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH, Austin A, Bell A, Bloch DA, Corey PN, Decker JL (1992) Derivation of the sledai. A disease activity index for lupus patients. Arthritis Rheum 35:630–640

    Article  CAS  PubMed  Google Scholar 

  30. Moeller MJ, Smeets B (2013) Novel target in the treatment of rpgn: the activated parietal cell. Nephrol Dial Transpl 28:489–492

    Article  CAS  Google Scholar 

  31. Keller F, Oehlenberg B, Kunzendorf U, Schwarz A, Offermann G (1989) Long-term treatment and prognosis of rapidly progressive glomerulonephritis. Clin Nephrol 31:190–197

    CAS  PubMed  Google Scholar 

  32. Rees A, Cameron J (1998) Crescentic glomerulonephritis. In: Cameron JS, Davison AM, Grunfeld JP, Kerr D, Ritz E (eds) Oxford textbook of clinical nephrology, vol 1992. Oxford University Press, New York, pp 418–438

  33. Ponticelli C, Imbasciati E, Brancaccio D, Tarantino A, Rivolta E (1974) Acute renal failure in systemic lupus erythematosus. Br Med J 3:716

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Zhu D, Qu Z, Tan Y, Yu F, Zhao MH (2011) Acute kidney injury in chinese patients with lupus nephritis: a large cohort study from a single center. Lupus 20:1557–1565

    Article  CAS  PubMed  Google Scholar 

  35. Yu F, Tan Y, Liu G, Wang S-x, Zou W-z, Zhao M-h (2009) Clinicopathological characteristics and outcomes of patients with crescentic lupus nephritis. Kidney Int 76:307–317

    Article  PubMed  Google Scholar 

  36. Schwartz MM, Roberts JL, Lewis EJ (1983) Necrotizing glomerulitis of systemic lupus erythematosus. Hum Pathol 14:158–167

    Article  CAS  PubMed  Google Scholar 

  37. Ferrario F, Napodano P, Giordano A, Gandini E, Boeri R, D’Amico G (1992) Peculiar type of focal and segmental lupus glomerulitis: glomerulonephritis or vasculitis? Contrib Nephrol 99:86

    CAS  PubMed  Google Scholar 

  38. Najafi CC, Korbet SM, Lewis EJ, Schwartz MM, Reichlin M, Evans J (2001) Significance of histologic patterns of glomerular injury upon long-term prognosis in severe lupus glomerulonephritis. Kidney Int 59:2156–2163

    Article  CAS  PubMed  Google Scholar 

  39. Hill GS, Delahousse M, Nochy D, Bariety J (2005) Class iv-s versus class iv-g lupus nephritis: clinical and morphologic differences suggesting different pathogenesis. Kidney Int 68:2288–2297

    Article  PubMed  Google Scholar 

  40. Mittal B, Hurwitz S, Rennke H, Singh AK (2004) New subcategories of class iv lupus nephritis: are there clinical, histologic, and outcome differences? Am J Kidney Dis 44:1050–1059

    Article  PubMed  Google Scholar 

  41. Schwartz MM, Korbet SM, Lewis EJ (2008) The prognosis and pathogenesis of severe lupus glomerulonephritis. Nephrol Dial Transpl 23:1298–1306

    Article  Google Scholar 

  42. Schwartz M, Korbet S, Katz R, Lewis E (2009) Evidence of concurrent immunopathological mechanisms determining the pathology of severe lupus nephritis. Lupus 18:149–158

    Article  CAS  PubMed  Google Scholar 

  43. Behara VY, Whittier WL, Korbet SM, Schwartz MM, Martens M, Lewis EJ (2010) Pathogenetic features of severe segmental lupus nephritis. Nephrol Dial Transpl 25:153–159

    Article  Google Scholar 

  44. Chen S, Tang Z, Zhang Y, Liu Z, Zhang H, Hu W (2013) Significance of histological crescent formation in patients with diffuse proliferative lupus nephritis. Am J Nephrol 38:445–452

    Article  CAS  PubMed  Google Scholar 

  45. Küster S, Apenberg S, Andrassy K, Ritz E (1992) Antineutrophil cytoplasmic antibodies in systemic lupus erythematosus. Contrib Nephrol 99:94

    PubMed  Google Scholar 

  46. Sen D, Isenberg DA (2003) Antineutrophil cytoplasmic autoantibodies in systemic lupus erythematosus. Lupus 12:651–658

    Article  CAS  PubMed  Google Scholar 

  47. Nasr SH, D’Agati VD, Park H-R, Sterman PL, Goyzueta JD, Dressler RM, Hazlett SM, Pursell RN, Caputo C, Markowitz GS (2008) Necrotizing and crescentic lupus nephritis with antineutrophil cytoplasmic antibody seropositivity. Clin J Am Soc Nephrol 3:682–690

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  48. Jennette JC, Xiao H, Falk RJ (2006) Pathogenesis of vascular inflammation by anti-neutrophil cytoplasmic antibodies. J Am Soc Nephrol 17:1235–1242

    Article  PubMed  Google Scholar 

  49. Couser WG (1988) Rapidly progressive glomerulonephritis: classification, pathogenetic mechanisms, and therapy. Am J Kidney Dis 11:449–464

    Article  CAS  PubMed  Google Scholar 

  50. Li X, Chen N (2013) Management of crescentic glomerulonephritis: what are the recent advances. Contrib Nephrol 181:229–239

    Article  PubMed  Google Scholar 

  51. Tang Z, Yang G, Yu C, Yu Y, Wang J, Hu W, Zeng C, Chen H, Liu Z, Li L (2008) Effects of mycophenolate mofetil for patients with crescentic lupus nephritis. Nephrology 13:702–707

    Article  CAS  PubMed  Google Scholar 

  52. Davies RJ, Sangle SR, Jordan NP, Aslam L, Lewis MJ, Wedgwood R, D’Cruz DP (2013) Rituximab in the treatment of resistant lupus nephritis: therapy failure in rapidly progressive crescentic lupus nephritis. Lupus 22:574–582

    Article  CAS  PubMed  Google Scholar 

  53. Sinha A, Puri K, Hari P, Dinda AK, Bagga A (2013) Etiology and outcome of crescentic glomerulonephritis. Indian Pediatr 50:283–288

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. National Clinical Research Centre of Kidney Desease, Jinling Hospital, Nanjing University School of Medicine, Nanjing, 210002, China

    Shasha Chen, Hao Chen, Zhengzhao Liu, Haitao Zhang, Weixin Hu, Zheng Tang & Zhihong Liu

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  1. Shasha Chen
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Correspondence to Zheng Tang.

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Chen, S., Chen, H., Liu, Z. et al. Pathological spectrums and renal prognosis of severe lupus patients with rapidly progressive glomerulonephritis. Rheumatol Int 35, 709–717 (2015). https://doi.org/10.1007/s00296-014-3140-x

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