Background: Rapidly progressive glomerulonephritis (RPGN) is characterized by a rapid deterioration of renal function and by extracapillary proliferation in >50% of glomeruli. The most common type of RPGN is “pauci-immune” glomerulonephritis caused by anti-neutrophil cytoplasmic antibodies-associated vasculitis (AAV). Summary: The incidence of AAV increases with age and pauci-immune glomerulonephritis is the most common diagnosis found in renal biopsies in the elderly population. Age was identified as an independent negative risk factor for both death and end-stage renal disease in AAV, and the mortality of older patients was uniformly higher than in younger patients in all retrospective studies. Early diagnosis may be difficult particularly in elderly patients with renal-limited disease but is important for the good outcome of the patients. Immunosuppressive treatment options include cyclophosphamide or rituximab combined with corticosteroids with or without plasma exchange in case of severe disease. Data from randomized trials are completely missing for patient aged >75 years. Based on retrospective studies, elderly patients seem to respond to immunosuppressive drugs just as younger patients are able to, but they are at a higher risk of adverse events. Key Messages: RPGN is relatively common in the elderly patients. Immunosuppressive treatment in older patients with AAV or RPGN may be useful but needs to be strictly individualized with all the risks taken into consideration. Further studies are needed to examine the role of novel therapeutic options in the elderly population with RPGN.

Keywords:
Anti-neutrophil cytoplasmic antibodies, Cyclophosphamide , Plasma exchange, Rituximab, Vasculitis
1.
Moroni G, Ponticelli C: Rapidly progressive crescentic glomerulonephritis: early treatment is a must. Autoimmun Rev 2014; 13: 723–729.
2.
Erwig LP, Rees AJ: Rapidly progressive glomerulonephritis. J Nephrol 1999; 12(suppl 2):S111–S119.
3.
Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, et al: 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum 2013; 65: 1–11.
4.
Watts RA, Mahr A, Mohammad AJ, Gatenby P, Basu N, Flores-Suárez LF: Classification, epidemiology and clinical subgrouping of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Nephrol Dial Transplant 2015; 30(suppl 1):i14–i22.
5.
Watts RA, Mooney J, Skinner J, Scott DG, MacGregor AJ: The contrasting epidemiology of granulomatosis with polyangiitis (Wegener’s) and microscopic polyangiitis. Rheumatology 2012; 51: 926–931.
6.
Jayne D: Chapter 8 – ANCA-Associated Vasculitis: Clinical Features and Treatment; in Mason JC, Pusey CD (eds): Handbook of Systemic Autoimmune Diseases. Elsevier, Vol. 7, 2007, pp 139–157.
7.
Moutzouris DA, Herlitz L, Appel GB, Markowitz GS, Freudenthal B, Radhakrishnan J, et al: Renal biopsy in the very elderly. Clin J Am Soc Nephrol 2009; 4: 1073–1082.
8.
Zhu P, Zhou FD, Zhao MH: The renal histopathology spectrum of elderly patients with kidney diseases: a study of 430 patients in a single Chinese center. Medicine (Baltimore) 2014; 93:e226.
9.
Rychlík I, Jancová E, Tesar V, Kolsky A, Lácha J, Stejskal J, et al: The Czech registry of renal biopsies. Occurrence of renal diseases in the years 1994–2000. Nephrol Dial Transplant 2004; 19: 3040–3049.
10.
McAdoo SP, Pusey CD: Anti-glomerular basement membrane disease. Clin J Am Soc Nephrol 2017; 12: 1162–1172.
11.
Little MA, Nightingale P, Verburgh CA, Hauser T, De Groot K, Savage C, et al: Early mortality in systemic vasculitis: relative contribution of adverse events and active vasculitis. Ann Rheum Dis 2010; 69: 1036–1043.
12.
Booth AD, Almond MK, Burns A, Ellis P, Gaskin G, Neild GH, et al: Outcome of ANCA-associated renal vasculitis: a 5-year retrospective study. Am J Kidney Dis 2003; 41: 776–784.
13.
Flossmann O, Berden A, de Groot K, Hagen C, Harper L, Heijl C, et al: Long-term patient survival in ANCA-associated vasculitis. Ann Rheum Dis 2011; 70: 488–494.
14.
Hoganson DD, From AM, Michet CJ: ANCA vasculitis in the elderly. J Clin Rheumatol 2008; 14: 78–81.
15.
Weiner M, Goh SM, Mohammad AJ, Hruskova Z, Tanna A, Bruchfeld A, et al: Outcome and treatment of elderly patients with ANCA-associated vasculitis. Clin J Am Soc Nephrol 2015; 10: 1128–1135.
16.
Bomback AS, Appel GB, Radhakrishnan J, Shirazian S, Herlitz LC, Stokes B, D’Agati VD, Markowitz GS: ANCA-associated glomerulonephritis in the very elderly. Kidney Int 2011; 79: 757–764.
17.
Haris Á, Polner K, Arányi J, Braunitzer H, Kaszás I, Mucsi I: Clinical outcomes of ANCA-associated vasculitis in elderly patients. Int Urol Nephrol 2014; 46: 1595–1600.
18.
West SC, Arulkumaran N, Ind PW, Pusey CD: Pulmonary-renal syndrome: a life threatening but treatable condition. Postgrad Med J 2013; 89: 274–283.
19.
Yates M, Watts RA, Bajema IM, Cid MC, Crestani B, Hauser T, et al: EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis 2016; 75: 1583–1594.
20.
Berden AE, Ferrario F, Hagen EC, Jayne DR, Jennette JC, Joh K, et al: Histopathologic classification of ANCA-associated glomerulonephritis. J Am Soc Nephrol 2010; 21: 1628–1636.
21.
Sumnu A, Gursu M, Ozturk S: Primary glomerular diseases in the elderly. World J Nephrol 2015; 4: 263–270.
22.
Guillevin L, Pagnoux C, Karras A, Khouatra C, Aumaître O, Cohen P, et al: Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis. N Engl J Med 2014; 371: 1771–1780.
23.
Hamour SM, Salama AD: ANCA comes of age-but with caveats. Kidney Int 2011; 79: 699–701.
24.
Harper L, Savage CO: ANCA-associated renal vasculitis at the end of the twentieth century – a disease of older patients. Rheumatology (Oxford) 2005; 44: 495–501.
25.
De Groot K, Harper L, Jayne DR, Flores Suarez LF, Gregorini G, Gross WL, et al; EUVAS (European Vasculitis Study Group): Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial. Ann Intern Med 2009; 150: 670–680.
26.
Harper L, Morgan MD, Walsh M, et al: Pulse versus daily oral cyclophosphamide for induction of remission in ANCA-associated vasculitis: long-term follow-up. Ann Rheum Dis 2012; 71: 955–960.
27.
Tesar V, Hruskova Z: Conventional induction and maintenance treatment of Antineutrophil cytoplasmic antibodies-associated vasculitis – still of value for our patients? Expert Opin Pharmacother 2015; 16: 1683–1702.
28.
Pepper RJ, Chanouzas D, Tarzi R, Little MA, Casian A, Walsh M, et al: Intravenous cyclophosphamide and plasmapheresis in dialysis-dependent ANCA-associated vasculitis. Clin J Am Soc Nephrol 2013; 8: 219–224.
29.
Jones RB, Tervaert JW, Hauser T, Luqmani R, Morgan MD, Peh CA, et al; European Vasculitis Study Group: Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med 2010; 363: 211–220.
30.
Stone JH, Merkel PA, Spiera R, Seo P, Langford CA, Hoffman GS, et al; RAVE-ITN Research Group: Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med 2010; 363: 221–232.
31.
Timlin H, Lee SM, Manno RL, Seo P, Geetha D: Rituximab for remission induction in elderly patients with ANCA-associated vasculitis. Semin Arthritis Rheum 2015; 45: 67–69.
32.
Mansfield N, Hamour S, Habib AM, Tarzi R, Levy J, Griffith M, et al: Prolonged disease-free remission following rituximab and low-dose cyclophosphamide therapy for renal ANCA-associated vasculitis. Nephrol Dial Transplant 2011; 26: 3280–3286.
33.
Jayne DR, Gaskin G, Rasmussen N, et al: Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J Am Soc Nephrol 2007; 18: 2180–2188.
34.
Walsh M, Casian A, Flossmann O, et al: Long-term follow-up of patients with severe ANCA-associated vasculitis comparing plasma exchange to intravenous methylprednisolone treatment is unclear. Kidney Int 2013; 84: 397–402.
35.
Walsh M, Catapano F, Szpirt W, et al: Plasma exchange for renal vasculitis and idiopathic rapidly progressive glomerulonephritis: a meta-analysis. Am J Kidney Dis 2011; 57: 566–574.
36.
Walsh M, Merkel PA, Peh CA, et al: Plasma exchange and glucocorticoid dosing in the treatment of anti-neutrophil cytoplasm antibody associated vasculitis (PEXIVAS): protocol for a randomized controlled trial. Trials 2013; 14: 73.
© 2018 S. Karger AG, Basel
2018
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.