Nierenbeteiligung bei ANCA-assoziierten Vaskulitiden

Abstract

In patients with ANCA-associated vasculitis renal involvement is frequently seen and the severity of renal manifestation is very important for therapeutic strategies and prognosis. Clinically rapid loss of renal function, nephritic sediment and proteinuria in a non-nephrotic range are characterizing a focal segmental necrotizing pauci-immune glomerulonephritis with extrarenal proliferations. Induction treatment depends on the severity of manifestations. With a normal renal function methotrexate can be used in combination with steroids. In patients with organ threatening involvement but creatinine below 500 µmol/l cyclophosphamide pulses or Rituximab should be used together with steroids, initially with i. v. pulses. Rituximab is more effective in PR3-ANCA vasculitis and should be used in relapsing disease, in young patients to avoid gonadal toxicity and in patients with an increased risk of malignancies. In patients on dialysis or with creatinine > 500 µmol/l plasma exchange should be added. Maintenance treatment (mainly with azathioprine) is necessary as at least 50 % of the patients develop relapses. Rituximab seems more effective, however it is not approved for maintenance treatment and no long-term data are available. Adjuvant treatment, long-term side effects and the increased incidence of cardiovascular events have to be included in the follow-up of vasculitis patients. In end-stage renal disease patients relapses occur but are more difficult to diagnose and treat with higher incidence of infections. Transplantation should be offered as patient and transplant survival is good.

Vaskulitiden sind seltene Erkrankungen, die durch einen Entzündungsprozess in den Blutgefäßen gekennzeichnet sind, wobei die Art und Lokalisation der befallenen Gefäße die Symptomatik bestimmt. Die Nieren können bei fast allen Vaskulitiden betroffen sein und führen über eine Biopsie nicht selten zur Diagnose. Trotz vieler neuer Studien bleiben die Erkrankungen eine therapeutische Herausforderung.

Schlüsselwörter

ANCA - Vaskulitis - Nierenbeteiligung - Induktionstherapie - Remission - Rezidiv

Key words

ANCA - vasculitis - renal manifestation - induction treatment - remission - relapse

• Literatur

• 1 Jennette JC, Falk RJ, Bacon PA. et al. 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum 2013; 65: 1-11
• 2 Schönermarck U, Csernok E, Gross WL. Pathogenesis of anti-neutrophil cytoplasmic antibody-associated vasculitis: challenges and solutions 2014. NDT 2015; 30 (01) 46-52
• 3 Lyons PA, Rayner TF, Trivedi S. et al. Genetically distinct subsets within ANCA-associated vasculitis. N Engl J Med 2012; 367: 214-223
• 4 Haubitz M. ANCA-associated vasculitis: diagnosis, clinical characteristics and treatment. Vasa 2007; 36: 81-89
• 5 Mukhtyar C, Guillevin L, Cid MC. et al. EULAR recommendations for the management of primary small and medium vessel vasculitis. Ann Rheum Dis 2009; 68: 310-317
• 6 Berden AE, Ferrario F, Hagen EC. et al. Histopathologic classification of ANCA-associated glomerulonephritis. JASN 2010; 21: 1628-1636
• 7 Vaglio A, Buzio C, Zwerina J. Eosinophilc granulomatosis with polyangiitis (Churg-Strauss): state of the art. Allergy 2013; 68: 261-263
• 8 Mouton L, Dunogue B, Guillevin L. Diagnosis and classification of eosinophilc granulomatosis with polyangiitis. J Autoimmun 2014; 48–49: 99-103
• 9 Mohammad AJ, Hot A, Arndt F. et al. Rituximab for the treatment of eosinophilic granulomatosis with polyangiitis (Churg-Strauss). Ann Rheumatic Disease 2016; 75: 396-401
• 10 Wechsler ME, Akuthota P, Jayne D. et al. Mepolizumab or placebo for eosinophilic granuloamtosis with polyangiitis. N Engl J Med 2017; 376: 1921-1931
• 11 De Groot K, Rasmussen N, Bacon PA. et al. Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic ANCA-associated vasculitis. Arthritis Rheum 2005; 52: 2461-2469
• 12 Guillevin L, Cordier J-F, Lhote F. et al. A prospective, multicenter, randomized trial comparing steroids and pulse cyclophosphamide versus steroids and oral cyclophosphamide in the treatment of generalized Wegener´s granulomatosis. Arthritis Rheum 1997; 40: 2187-2198
• 13 Haubitz M, Schellong S, Göbel U. et al. Intravenous pulse administration of cyclophosphamide versus daily oral treatment in patients with ANCA-associated vasculitis and renal involvement: a prospective, randomized study. Arthritis and Rheum 1998; 41: 1835-1844
• 14 Groot K, Harper L, Jayne DR. et al. Pulse versus daily oral cyclophosphamide for induction of remission in ANCA-associated vasculitis: a randomized trial. Ann Int Med 2009; 150: 670-678
• 15 Lovric S, Erdbruegger U, Kuempers P. et al. Rituximab as rescue therapy in ANCA associated vasculitis: single centre experience with fifteen patients. Nephrol Dial Transplant 2009; 24: 179-185
• 16 Jones RB, Ferraro AJ, Chaudhry AN. et al. A multicenter survey of rituximab therapy for refractory ANCA-associated vasculitis. Arthritis Rheum 2009; 60: 2156-2168
• 17 Stone JH, Merkel PA, Spiera R. et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. New Engl J Med 2010; 363: 221-232
• 18 Jones RB, Tervaert JW, Hauser T. et al. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med 2010; 363: 211-220
• 19 Moosig F, Aries PM, de Groot K. et al. Stellenwert der B-Zell-gerichteten Therapie bei Granulomatose mit Polyangiitis und mikroskopischer Polyangiitis. DMW 2014; 139: 2248-2253
• 20 Birck R. Neues in der Immunsuppression von Vaskulitiden. Mycophenolat-Mofetil. Der Nephrologe 2012; 7: 222-226
• 21 Szpirt WM. Plasma exchange in antineutrophil cytoplasmic antibody-ssociated vasculitis – a 25-year perspective. Nephrol Dial Transplant 2015; 30: 146-149
• 22 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
• 23 Jayne DRW, Brachfeld AN, Harper L. et al. Randomized trial of C5a receptor inhibitor avacopan in ANCA-associated vasculitis. J Am Soc Nephrol 2017; 28: 2756-2767
• 24 Walsh M, Merkel PA, Marh A. et al. Effects of duration of glucocorticoid therapy on relapse rate in ANCA-associated vasculitis: a meta-analysis. Arthritis Care Res 2010; 62: 1166-1173
• 25 Jayne D, Rasmussen N, Andrassy K. et al. A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med 2003; 349: 36-44
• 26 Karras A, Pagnoux C, Haubitz M. et al. Randomised controlled trial of prolonged treatment in the remission phase of ANCA-associated vasculitis. Ann Rheum Dis 2017; 76: 1662-1668
• 27 Pagnoux C, Mahr A, Hamidou MA. et al. Azathioprine or methotrexat maintance for ANCA-associated vasculitis. N Engl J Med 2008; 359: 2790-2803
• 28 Hiemstra TF, Walsh M, Mahr A. et al. Mycophenolate mofetil vs azathioprine for remission maintenance in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized controlled trial. J Am Med Assoc 2010; 304: 2381-2388
• 29 Haubitz M, Koch KM, Brunkhorst R. Cyclosporin for the prevention of disease reactivation in relapsing ANCA-associated vasculitis. Nephrol Dial Transplant 1998; 13: 2074-2076
• 30 Guillevin L, Pagnoux C, Karras A. et al. Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis. New Engl J Med 2014; 371: 1771-1780
• 31 Walsh M, Flossmann O, Berden A. et al. Risk factors for relapse of antineutropil cytoplasmic antibody-associated vasculitis. Arthritis Rheum 2012; 64: 542-548
• 32 Pendergraft W, Cortazar FC, Wenger J. et al. Long-term maintenance therapy using rituximab-induced continuous B-cell depletion in patients with ANCA vasculitis. Clin J Am Soc Nephrol 2014; 9: 736-744
• 33 Moiseev S, Novikov P, Jayne D. et al. End-stage renal disease in ANCA-associated vasculitis. Nephrol Dial Transplant 2017; 32: 248-253