RSS-Feed abonnieren
DOI: 10.1055/s-0031-1275660
© Georg Thieme Verlag KG Stuttgart · New York
Nierenbeteiligung bei systemischen Vaskulitiden
Renal Manifestations of Systemic VasculitisPublikationsverlauf
Publikationsdatum:
15. April 2011 (online)
![](https://www.thieme-connect.de/media/rheuma/201105/lookinside/thumbnails/10.1055-s-0031-1275660-1.jpg)
Zusammenfassung
Systemische Vaskulitiden sind eine heterogene Gruppe von Autoimmunerkrankungen, in deren Verlauf durch entzündliche Gefäßveränderungen eine Gewebszerstörung und ein Funktionsverlust der betroffenen Organe auftreten. Die Einteilung der Vaskulitiden erfolgt nach ätiologischen, morphologischen und immunologischen Kriterien. Neben der Unterscheidung zwischen primären und sekundären Vaskulitisformen, die im Rahmen anderer Erkrankungen auftreten, unterteilt man nach den betroffenen Gefäßabschnitten in Klein-, Mittel- und Großgefäßvaskulitiden. Pathogenetisch bedeutsam ist die Abgrenzung der Immunkomplex bedingten gegenüber den pauci-immunen Vaskulitiden. Tritt im Rahmen einer systemischen Vaskulitis eine Beteiligung der Nieren auf, so ist die rapid progressive Glomerulonephritis (RPGN) mit einem Verlust der Organfunktion eine bedrohliche Komplikation und bedarf einer raschen Diagnostik und Therapie. Das charakteristische histologische Bild einer ANCA-assoziierten Vaskulitis ist eine schwere Entzündungsreaktion in Form halbmondbildender glomerulärer Nekrosen und eine Vaskulitis der kleinen Gefäße. Es liegen evidenzbasierte Therapieprotokolle für die Remissionsinduktion und Remissionserhaltung vor. Grundsätzlich wird initial eine höherpotente Immunsuppression, bei kritischer Organbeteiligung mit Prednisolon und Cyclophosphamid durchgeführt. Bei refraktären Verläufen ist die Behandlung mit einem CD20-Antikörper (Rituximab) etabliert. Zur Remissionserhaltung kommen anschließend Azathioprin, Methotrexat oder Leflunomid in Betracht. Von klinischer Bedeutung ist die Vermeidung erkrankungs- und therapieassoziierter Komplikationen (Infektionen, gonadale Insuffizienz bei Cyclophosphamidtherapie, Steroid-induzierte Osteoporose und Atherosklerose). Auch immunkomplexbedingte Vaskulitiden können zu einer Nierenbeteiligung (RPGN) führen, die jedoch meist weniger aggressiv verläuft. Für die Kryoglobulinämie ist eine Assoziation zu einer aktiven Hepatitis C bekannt, wobei die erfolgreiche Therapie der Virusinfektion zu einer Remission der Vaskulitis führt. Großgefäßvaskulitiden manifestieren sich meist nur indirekt an den Nieren. Eine Beteiligung der Nierenarterien und eine konsekutive renale Hypertonie sind möglich.
Abstract
The systemic vasculitides are a heterogenous group of autoimmune disorders, characterised by vessel wall inflammation leading to tissue damage and consecutive loss of function in the dependent organ systems. Vasculitides are classified by aetiological, morphological and immunological criteria. Primary and secundary vasculitis are distinguished diseases and they are categorised according to different sizes of the involved vessels into small, medium and large vessel vasculitis. Immunologically important are 2 different types of vasculitis, immune complex-mediated and pauci immune vasculitis. Renal involvement with rapid progressive glomerulonephritis (RPGN) is a life-threatening complication and needs to be diagnosed and treated immediately. Necrotising crescentic glomerulonephritis is histologically characteristic for ANCA-associated vasculitis. There are evidence-based protocols for induction and maintenance therapy. Combined treatment with steroids and cyclophosphamide is mandatory for critical organ involvement. B-cell-depleting therapy with rituximab is an efficient alternative. Azathioprine, methotrexate and leflunomide are recommended for maintaining remission. Infections, related to therapy or disease, are of particular clinical interest, because they are responsible for increased mortality during the early course of disease. Furthermore, gonadal insufficiency after cyclophosphamide therapy and steroid-induced osteoporosis should be prevented. Immune complex-mediated vasculitis could also cause renal involvement, although the course of glomerulonephritis is less agressive. Kryoglobulinaemic vasculitis is often associated with active hepatitis C infection and remission could be achieved by elimination of virus with interferon alpha. Renal involvement in large vessel vasculitis is mainly attributed to ischaemia and consecutive renal hypertension.
Schlüsselwörter
systemische Vaskulitis - Nierenbeteiligung - Pathogenese - Therapie
Key words
systemic vasculitis - renal involvement - pathogenesis - therapy
Literatur
- 1 Bloch DA, Michel BA, Hunder GG. et al . The American College of Rheumatology 1990 criteria for the classification of vasculitis. Patients and methods. Arthritis Rheum. 1990; 33 1068-1073
- 2 Jennette JC, Falk RJ, Andrassy K. et al . Nomenclature of systemic vasculitides. Proposal of an international consensus conference. Arthritis Rheum. 1994; 37 187-192
- 3 Watts R, Lane S, Hanslik T. et al . 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
- 4 Booth AD, Almond MK, Burns A. et al . Outcome of ANCA-associated renal vasculitis: a 5-year retrospective study. Am J Kidney Dis. 2003; 41 776-784
- 5 Stilmant MM, Bolton WK, Sturgill BC. et al . Crescentic glomerulonephritis without immune deposits: clinicopathologic features. Kidney Int. 1979; 15 184-195
- 6 Kallenberg CG. Antineutrophil cytoplasmic antibodies (ANCA) and vasculitis. Clin Rheumatol. 1990; 9 132-135
- 7 Savige JA, Paspaliaris B, Silvestrini R. et al . A review of immunofluorescent patterns associated with antineutrophil cytoplasmic antibodies (ANCA) and their differentiation from other antibodies. J Clin Pathol. 1998; 51 568-575
- 8 Jennette JC, Falk RJ. New insight into the pathogenesis of vasculitis associated with antineutrophil cytoplasmic autoantibodies. Curr Opin Rheumatol. 2008; 20 55-60
- 9 Kallenberg CG. Pathogenesis of PR3-ANCA associated vasculitis. J Autoimmun. 2008; 30 29-36
- 10 Falk RJ, Terrell RS, Charles LA. et al . Anti-neutrophil cytoplasmic autoantibodies induce neutrophils to degranulate and produce oxygen radicals in vitro. Proc Natl Acad Sci U S A. 1990; 87 4115-4119
- 11 Falk RJ, Hogan S, Carey TS. et al . Clinical course of anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis and systemic vasculitis. The Glomerular Disease Collaborative Network. Ann Intern Med. 1990; 113 656-663
- 12 Boomsma MM, Stegeman CA, van der Leij MJ. et al . Prediction of relapses in Wegener's granulomatosis by measurement of antineutrophil cytoplasmic antibody levels: a prospective study. Arthritis Rheum. 2000; 43 2025-2033
- 13 Morita S, Ueda Y, Eguchi K. Anti-thyroid drug-induced ANCA-associated vasculitis: a case report and review of the literature. Endocr J. 2000; 47 467-470
- 14 Stegeman CA, Tervaert JW, Sluiter WJ. et al . Association of chronic nasal carriage of Staphylococcus aureus and higher relapse rates in Wegener granulomatosis. Ann Intern Med. 1994; 120 12-17
- 15 Pendergraft WF, Preston GA, Shah RR. et al . Autoimmunity is triggered by cPR-3 (105-201), a protein complementary to human autoantigen proteinase-3. Nat Med. 2004; 10 72-79
- 16 Eisenberger U, Fakhouri F, Vanhille P. et al . ANCA-negative pauci-immune renal vasculitis: histology and outcome. Nephrol Dial Transplant. 2005; 20 1392-1399
- 17 de Lind van Wijngaarden RA, Hauer HA, Wolterbeek R. et al . 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
- 18 Berden AE, Ferrario F, Hagen EC. et al . Histopathologic classification of ANCA-associated glomerulonephritis. J Am Soc Nephrol. 2010; 21 1628-1636
- 19 Watts RA, Scott DGI. Epidemiology of Vasculitis.. In: Ball G. V. BSL ed, Vasculitis. 2nd ed. Oxford: Oxford University Press; 2008: 7-22
- 20 Lane SE, Watts RA, Shepstone L. et al . Primary systemic vasculitis: clinical features and mortality. QJM. 2005; 98 97-111
- 21 Savage CO, Winearls CG, Evans DJ. et al . Microscopic polyarteritis: presentation, pathology and prognosis. Q J Med. 1985; 56 467-483
- 22 Serra A, Cameron JS, Turner DR. et al . Vasculitis affecting the kidney: presentation, histopathology and long-term outcome. Q J Med. 1984; 53 181-207
- 23 Balow JA, Fauci AS. Vasculitis diseases of the kidney.. In: Schrier R. W. GWJ ed, Diseases of the Kidney. Boston: Little Brown; 1997: 1851-1878
- 24 Lhote F, Cohen P, Guillevin L. Polyarteritis nodosa, microscopic polyangiitis and Churg-Strauss syndrome. Lupus. 1998; 7 238-258
- 25 Guillevin L, Durand-Gasselin B, Cevallos R. et al . Microscopic polyangiitis: clinical and laboratory findings in eighty-five patients. Arthritis Rheum. 1999; 42 421-430
- 26 Watts RA, Carruthers DM, Scott DG. Epidemiology of systemic vasculitis: changing incidence or definition?. Semin Arthritis Rheum. 1995; 25 28-34
- 27 Falk RJ, Gross WL, Guillevin L. et al . Granulomatosis with polyangiitis (Wegener's): An alternative name for Wegener's granulomatosis. Ann Rheum Dis. 70 704
- 28 Fauci AS, Haynes BF, Katz P. et al . Wegener's granulomatosis: prospective clinical and therapeutic experience with 85 patients for 21 years. Ann Intern Med. 1983; 98 76-85
- 29 Hoffman GS, Kerr GS, Leavitt RY. et al . Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med. 1992; 116 488-498
- 30 Novak RF, Christiansen RG, Sorensen ET. The acute vasculitis of Wegener's granulomatosis in renal biopsies. Am J Clin Pathol. 1982; 78 367-371
- 31 Franssen CF, Gans RO, Arends B. et al . Differences between anti-myeloperoxidase- and anti-proteinase 3-associated renal disease. Kidney Int. 1995; 47 193-199
- 32 Abril A, Calamia KT, Cohen MD. The Churg-Strauss syndrome (allergic granulomatous angiitis): review and update. Semin Arthritis Rheum. 2003; 33 106-114
- 33 Churg J, Strauss LCP. Allergic granulomatosis, allergic angiitis, and periarteritis nodosa. Am J Pathol. 1951; 27 277-301
- 34 Lanham JG, Elkon KB, Pusey CD. et al . Systemic vasculitis with asthma and eosinophilia: a clinical approach to the Churg-Strauss syndrome. Medicine (Baltimore). 1984; 63 65-81
- 35 Masi AT, Hunder GG, Lie JT. et al . The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum. 1990; 33 1094-1100
- 36 Mahr A, Guillevin L, Poissonnet M. et al . Prevalences of polyarteritis nodosa, microscopic polyangiitis, Wegener's granulomatosis, and Churg-Strauss syndrome in a French urban multiethnic population in 2000: a capture-recapture estimate. Arthritis Rheum. 2004; 51 92-99
- 37 Sinico RA, Di Toma L, Maggiore U. et al . Renal involvement in Churg-Strauss syndrome. Am J Kidney Dis. 2006; 47 770-779
- 38 Clutterbuck EJ, Evans DJ, Pusey CD. Renal involvement in Churg-Strauss syndrome. Nephrol Dial Transplant. 1990; 5 161-167
- 39 Bosch X, Guilabert A, Espinosa G. et al . Treatment of antineutrophil cytoplasmic antibody associated vasculitis: a systematic review. JAMA. 2007; 298 655-669
- 40 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
- 41 de Groot K, Adu D, Savage CO. et al . The value of pulse cyclophosphamide in ANCA-associated vasculitis: meta-analysis and critical review. Nephrol Dial Transplant. 2001; 16 2018-2027
- 42 de Groot K, Harper L, Jayne DR. et al . 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
- 43 Guillevin L, Cordier JF, 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
- 44 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
- 45 de Groot K, Rasmussen N, Bacon PA. et al . Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2005; 52 2461-2469
- 46 Silva F, Specks U, Kalra S. et al . 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
- 47 Walters GD, Willis NS, Craig JCCP. Interventions for renal vasculitis in adults. A systematic review. BMC Nephrol. 2010; 11 12
- 48 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
- 49 Stone JH, Merkel PA, Spiera R. et al . Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010; 363 221-232
- 50 Jones RB, Tervaert JW, Hauser T. et al . Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med. 2010; 363 211-220
- 51 Jones RB, Ferraro AJ, Chaudhry AN. et al . A multicenter survey of rituximab therapy for refractory antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2009; 60 2156-2168
- 52 Group TWsGETWR . Etanercept plus standard therapy for Wegener's granulomatosis. N Engl J Med. 2005; 352 351-361
- 53 Mukhtyar C, Luqmani R. Current state of tumour necrosis factor {alpha} blockade in Wegener's granulomatosis. Ann Rheum Dis. 2005; 64 (S 04) iv31-iv36
- 54 Morgan MD, Drayson MT, Savage CO. et al . Addition of infliximab to standard therapy for ANCA-associated vasculitis. Nephron. 2011; 117 c89-c97
- 55 Laurino S, Chaudhry A, Booth A. et al . Prospective study of TNFalpha blockade with adalimumab in ANCA-associated systemic vasculitis with renal involvement. Nephrol Dial Transplant. 2010; 25 3307-3314
- 56 Flossmann O, Baslund B, Bruchfeld A. et al . Deoxyspergualin in relapsing and refractory Wegener's granulomatosis. Ann Rheum Dis. 2009; 68 1125-1130
- 57 Schmitt WH, Hagen EC, Neumann I. et al . Treatment of refractory Wegener's granulomatosis with antithymocyte globulin (ATG): an open study in 15 patients. Kidney Int. 2004; 65 1440-1448
- 58 Walsh M, Chaudhry A, Jayne D. Long-term follow-up of relapsing/refractory anti-neutrophil cytoplasm antibody associated vasculitis treated with the lymphocyte depleting antibody alemtuzumab (CAMPATH-1 H). Ann Rheum Dis. 2008; 67 1322-1327
- 59 Reinhold-Keller E, Fink CO, Herlyn K. et al . High rate of renal relapse in 71 patients with Wegener's granulomatosis under maintenance of remission with low-dose methotrexate. Arthritis Rheum. 2002; 47 326-332
- 60 Metzler C, Miehle N, Manger K. et al . Elevated relapse rate under oral methotrexate versus leflunomide for maintenance of remission in Wegener's granulomatosis. Rheumatology (Oxford). 2007; 46 1087-1091
- 61 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. JAMA. 2010; 304 2381-2388
- 62 Stegeman CA, Tervaert JW, de Jong PE. et al . Trimethoprim-sulfamethoxazole (co-trimoxazole) for the prevention of relapses of Wegener's granulomatosis. Dutch Co-Trimoxazole Wegener Study Group. N Engl J Med. 1996; 335 16-20
- 63 Walsh M, Merkel PA, Mahr A. et al . Effects of duration of glucocorticoid therapy on relapse rate in antineutrophil cytoplasmic antibody-associated vasculitis: A meta-analysis. Arthritis care & research. 2010; 62 1166-1173
- 64 Gardner-Medwin JM, Dolezalova P, Cummins C. et al . Incidence of Henoch-Schönlein purpura, Kawasaki disease, and rare vasculitides in children of different ethnic origins. Lancet. 2002; 360 1197-1202
- 65 Shrestha S, Sumingan N, Tan J. et al . Henoch Schönlein purpura with nephritis in adults: adverse prognostic indicators in a UK population. QJM. 2006; 99 253-265
- 66 Narchi HCP. Risk of long term renal impairment and duration of follow up recommended for Henoch-Schonlein purpura with normal or minimal urinary findings: a systematic review. Arch Dis Child. 2005; 90 916-920
- 67 Davin JC, Ten Berge IJ, Weening JJ. What is the difference between IgA nephropathy and Henoch-Schönlein purpura nephritis?. Kidney Int. 2001; 59 823-834
- 68 Huber AM, King J, McLaine P. et al . A randomized, placebo-controlled trial of prednisone in early Henoch Schönlein Purpura [ISRCTN85109383]. BMC Med. 2004; 2 7
- 69 Pillebout E, Alberti C, Guillevin L. et al . Addition of cyclophosphamide to steroids provides no benefit compared with steroids alone in treating adult patients with severe Henoch Schonlein Purpura. Kidney Int. 2010; 78 495-502
- 70 Brouet JC, Clauvel JP, Seligmann M. [Cryoglobulinemias. Clinical and biological correlations]. Ann Med Interne (Paris). 1975; 126 563-567
- 71 Della Rossa A, Ferri C, Bombardieri S. Y S. From essential mixed cryoglobulinemia to virus induced autoimmunity: ten years of research in mixed cryoglobulinemia. In: The decade of autoimmunity. Amsterdam: Elsevier Science; 1999: 235-243
- 72 Trejo O, Ramos-Casals M, García-Carrasco M. et al . Cryoglobulinemia: study of etiologic factors and clinical and immunologic features in 443 patients from a single center. Medicine (Baltimore). 2001; 80 252-262
- 73 Tarantino A, Campise M, Banfi G. et al . Long-term predictors of survival in essential mixed cryoglobulinemic glomerulonephritis. Kidney Int. 1995; 47 618-623
- 74 Gatta A, Giannini C, Lampertico P. et al . Hepatotropic viruses: new insights in pathogenesis and treatment. Clin Exp Rheumatol. 2008; 26 S33-S38
- 75 Braun A, Neumann T, Oelzner P. et al . Cryoglobulinaemia type III with severe neuropathy and immune complex glomerulonephritis: remission after plasmapheresis and rituximab. Rheumatol Int. 2008; 28 503-506
- 76 Zaja F, De Vita S, Mazzaro C. et al . Efficacy and safety of rituximab in type II mixed cryoglobulinemia. Blood. 2003; 101 3827-3834
- 77 Matteson EL. Notes on the history of eponymic idiopathic vasculitis: the diseases of Henoch and Schönlein, Wegener, Churg and Strauss, Horton, Takayasu, Behçet, and Kawasaki. Arthritis Care Res. 2000; 13 237-245
- 78 Henegar C, Pagnoux C, Puéchal X. et al . A paradigm of diagnostic criteria for polyarteritis nodosa: analysis of a series of 949 patients with vasculitides. Arthritis Rheum. 2008; 58 1528-1538
- 79 Guillevin L, Pagnoux C, Teixeira L. Polyarteritis nodosa and microscopic polyangiitis. Oxford: Oxford University Press; 2008
- 80 Frohnert PP, Sheps SG. Long-term follow-up study of periarteritis nodosa. Am J Med. 1967; 43 8-14
- 81 Gayraud M, Guillevin L, le Toumelin P. et al . Long-term follow-up of polyarteritis nodosa, microscopic polyangiitis, and Churg-Strauss syndrome: analysis of four prospective trials including 278 patients. Arthritis Rheum. 2001; 44 666-675
- 82 Pagnoux C, Cohen P, Guillevin L. Vasculitides secondary to infections. Clin Exp Rheumatol. 2006; 24 S71-S81
- 83 Medvedev G, Al-Shamari AE, Copland MA. et al . Isolated renal giant cell arteritis. Am J Kidney Dis. 2002; 40 658-661
- 84 Hall S, Barr W, Lie JT. et al . Takayasu arteritis. A study of 32 North American patients. Medicine (Baltimore). 1985; 64 89-99
- 85 Flossmann O, Berden A, de Groot K. et al . Long-term patient survival in ANCA-associated vasculitis. Ann Rheum Dis. 2010;
- 86 Little MA, Nightingale P, Verburgh CA. et al . Early mortality in systemic vasculitis: relative contribution of adverse events and active vasculitis. Ann Rheum Dis. 2010; 69 1036-1043
- 87 Clowse ME, Behera MA, Anders CK. et al . Ovarian preservation by GnRH agonists during chemotherapy: a meta-analysis. Journal of women's health (2002). 2009; 18 311-319
- 88 de Leeuw K, Sanders JS, Stegeman C. et al . Accelerated atherosclerosis in patients with Wegener's granulomatosis. Ann Rheum Dis. 2005; 64 753-759
- 89 Ruster C, Wolf G. Renin-angiotensin-aldosterone system and progression of renal disease. J Am Soc Nephrol. 2006; 17 2985-2991
Korrespondenzadresse
Dr. Thomas Neumann
Universitätsklinikum Jena
Klinik für Innere Medizin III
Rheumatologie/Osteologie
Erlanger Allee 101
07747 Jena
Telefon: +49/0364/193 245 95
Fax: +49/0364/193 243 62
eMail: Thomas.Neumann@med.uni-jena.de