Background/Aims: Anti-neutrophil cytoplasmic autoantibody-associated vasculitis (AAV) is a cause of biopsy-proven acute kidney injury, more common in the elderly. Treatment requires immunosuppression, which can have significant toxic effects. The aim of this study was to assess whether morbidity and mortality that are associated with immunosuppression for AAV varied with age. Methods: A retrospective review of 232 patients given induction therapy with prednisolone and cyclophosphamide was conducted. Information was collected on baseline characteristics (including requirement for dialysis at presentation) and the occurrence of leukopenia, infection, end-stage renal disease and death during follow-up. Results: Median follow-up was 51 months. Older patients (aged ≥70 years) were treated with lower total cyclophosphamide doses than those aged <70 years (mean 7.3 g (SD 4.4) vs. 10.7 g (SD 7.4), respectively). Increasing age was associated with an increased risk of leukopenia (odds ratio (OR) 1.50; 95% confidence interval (CI) 1.20-1.86; p < 0.001), and older patients were more likely to develop infections in the first year (OR 1.87; 95% CI 1.1-3.2). Older patients were also significantly more likely to require dialysis at presentation (OR 1.66; 95% CI 1.13-2.5) and longer term. After multivariable adjustment, age and requirement for dialysis at presentation were significant predictors of death (hazard ratio (HR) per year of age 1.07; 95% CI 1.03-1.11; p < 0.001 and HR 2.2; 95% CI 1.10-4.38; p = 0.03, respectively). Conclusions: Among patients treated with prednisolone and cyclophosphamide, increasing age and dialysis dependency were associated with worse survival. Older patients were more likely to develop treatment-related complications despite lower cumulative doses of immunosuppression. Morbidity and mortality associated with treatment must therefore be carefully balanced against that associated with the disease process itself.

Kaplan-Pavlovcic S, Cerk K, Kveder R, Lindic J, Vizjak A: Clinical prognostic factors of renal outcome in anti-neutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis in elderly patients. Nephrol Dial Transplant 2003;18(suppl 5):v5-v7.
Moutzouris DA, Herlitz L, Appel GB, Markowitz GS, Freudenthal B, Radhakrishnan J, D'Agati VD: Renal biopsy in the very elderly. Clin J Am Soc Nephrol 2009;4:1073-1082.
Hamour SM, Salama AD: ANCA comes of age-but with caveats. Kidney Int 2011;79:699-701.
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.
Hogan J, Avasare R, Radhakrishnan J: Is newer safer? Adverse events associated with first-line therapies for ANCA-associated vasculitis and lupus nephritis. Clin J Am Soc Nephrol 2014;9:1657-1667.
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.
Pepper RJ, Chanouzas D, Tarzi R, Little MA, Casian A, Walsh M, Pusey CD, Harper L, Salama AD: Intravenous cyclophosphamide and plasmapheresis in dialysis-dependent ANCA-associated vasculitis. Clin J Am Soc Nephrol 2013;8:219-224.
McGregor JG, Hogan SL, Hu Y, Jennette CE, Falk RJ, Nachman PH: Glucocorticoids and relapse and infection rates in anti-neutrophil cytoplasmic antibody disease. Clin J Am Soc Nephrol 2012;7:240-247.
Novack SN, Pearson CM: Cyclophosphamide therapy in Wegener's granulomatosis. N Engl J Med 1971;284:938-942.
Goupil R, Brachemi S, Nadeau-Fredette AC, Déziel C, Troyanov Y, Lavergne V, Troyanov S: Lymphopenia and treatment-related infectious complications in ANCA-associated vasculitis. Clin J Am Soc Nephrol 2013;8:416-423.
de Groot K, Harper L, Jayne DR, Flores Suarez LF, Gregorini G, Gross WL, Luqmani R, Pusey CD, Rasmussen N, Sinico RA, Tesar V, Vanhille P, Westman K, Savage CO: 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.
Chen M, Yu F, Zhang Y, Zhao MH: Antineutrophil cytoplasmic autoantibody-associated vasculitis in older patients. Medicine (Baltimore) 2008;87:203-209.
Weiner M, Goh SM, Mohammad AJ, Hruskova Z, Tanna A, Bruchfeld A, Selga D, Chocova Z, Westman K, Eriksson P, Pusey CD, Tesar V, Salama AD, Segelmark M: Outcome and treatment of elderly patients with ANCA-associated vasculitis. Clin J Am Soc Nephrol 2015;10:1128-1135.
Jayne DR, Gaskin G, Rasmussen N, Abramowicz D, Ferrario F, Guillevin L, Mirapeix E, Savage CO, Sinico RA, Stegeman CA, Westman KW, van der Woude FJ, de Lind van Wijngaarden RA, Pusey CD: Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J Am Soc Nephrol 2007;18:2180-2188.
Lionaki S, Falk RJ: Removing antibody and preserving glomeruli in ANCA small-vessel vasculitis. J Am Soc Nephrol 2007;18:1987-1989.
Lionaki S, Hogan SL, Jennette CE, Hu Y, Hamra JB, Jennette JC, Falk RJ, Nachman PH: The clinical course of ANCA small-vessel vasculitis on chronic dialysis. Kidney Int 2009;76:644-651.
Haris A, Polner K, Aranyi J, Braunitzer H, Kaszas I, Mucsi I: Clinical outcomes of ANCA-associated vasculitis in elderly patients. Int Urol Nephrol 2014;46:1595-1600.
Harper L, Morgan MD, Walsh M, Hoglund P, Westman K, Flossmann O, Tesar V, Vanhille P, de Groot K, Luqmani R, Flores-Suarez LF, Watts R, Pusey C, Bruchfeld A, Rasmussen N, Blockmans D, Savage CO, Jayne D: Pulse versus daily oral cyclophosphamide for induction of remission in ANCA-associated vasculitis: long-term follow-up. Ann Rheum Dis 2012;71:955-960.
Weidner S, Geuss S, Hafezi-Rachti S, Wonka A, Rupprecht HD: ANCA-associated vasculitis with renal involvement: an outcome analysis. Nephrol Dial Transplant 2004;19:1403-1411.
de Joode AA, Sanders JS, Stegeman CA: Renal survival in proteinase 3 and myeloperoxidase ANCA-associated systemic vasculitis. Clin J Am Soc Nephrol 2013;8:1709-1717.
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.
Silva F, Specks U, Kalra S, Hogan MC, Leung N, Sethi S, Fervenza FC: Mycophenolate mofetil for induction and maintenance of remission in microscopic polyangiitis with mild to moderate renal involvement - a prospective, open-label pilot trial. Clin J Am Soc Nephrol 2010;5:445-453.
de Joode AA, Sanders JS, Smid WM, Stegeman CA: Plasmapheresis rescue therapy in progressive systemic ANCA-associated vasculitis: single-center results of stepwise escalation of immunosuppression. J Clin Apher 2014;29:266-272.
Collins R, MacMahon S: Reliable assessment of the effects of treatment on mortality and major morbidity, I: clinical trials. Lancet 2001;357:373-380.
MacMahon S, Collins R: Reliable assessment of the effects of treatment on mortality and major morbidity, II: observational studies. Lancet 2001;357:455-462.
Tarzi RM, Pusey CD: Vasculitis: risks and rewards of treating elderly patients with vasculitis. Nat Rev Nephrol 2011;7:253-255.
Jones RB, Tervaert JW, Hauser T, Luqmani R, Morgan MD, Peh CA, Savage CO, Segelmark M, Tesar V, van Paassen P, Walsh D, Walsh M, Westman K, Jayne DR: Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med 2010;363:211-220.
Stone JH, Merkel PA, Spiera R, Seo P, Langford CA, Hoffman GS, Kallenberg CG, St Clair EW, Turkiewicz A, Tchao NK, Webber L, Ding L, Sejismundo LP, Mieras K, Weitzenkamp D, Ikle D, Seyfert-Margolis V, Mueller M, Brunetta P, Allen NB, Fervenza FC, Geetha D, Keogh KA, Kissin EY, Monach PA, Peikert T, Stegeman C, Ytterberg SR, Specks U: Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med 2010;363:221-232.
Alberici F, Jayne DR: Impact of rituximab trials on the treatment of ANCA-associated vasculitis. Nephrol Dial Transplant 2014;29:1151-1159.
Kronbichler A, Jayne DR: Con: should all patients with anti-neutrophil cytoplasmic antibody-associated vasculitis be primarily treated with rituximab? Nephrol Dial Transplant 2015;30:1075-1081.
Specks U: Pro: should all patients with anti-neutrophil cytoplasmic antibody-associated vasculitis be primarily treated with rituximab? Nephrol Dial Transplant 2015;30:1083-1087.
Tesar V: Moderator's view: should all patients with ANCA-associated vasculitis be primarily treated with rituximab? Nephrol Dial Transplant 2015;30:1088-1090.
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