Nierenbeteiligung bei Kollagenosen

Zusammenfassung

Renale Manifestationen bei Kollagenosen unterscheiden sich erheblich in Pathogenese, Häufigkeit sowie in ihrer Bedeutung für Prognose und Therapie der zugrunde liegenden Erkrankung. Die Lupusnephritis bestimmt entscheidend Prognose und Therapie des systemischen Lupus erythematodes und bedarf zur gezielten Therapieplanung der histologischen Abklärung. Die Induktionstherapie der proliferativen Lupusnephritis wird in der Regel mit einer low-dose Cyclophosphamid-Puls-Therapie in Kombination mit Glukokortikoiden durchgeführt. Dem schließt sich eine längere Phase der Remissionserhaltung mit Azathioprin an. Bei Unverträglichkeit oder Unwirksamkeit dieser Substanzen kann alternativ sowohl im Rahmen der Remissionsinduktion als auch der Remissionserhaltung Mycophenolat-Mofetil (MMF) eingesetzt werden. Bei gegenüber der Standard-Therapie und MMF therapierefraktären Verläufen ist der Einsatz von Rituximab Erfolg versprechend. Das Antiphospholipidsyndrom (APS) kann sich an den Nieren u. a. in Form von Nierenarterienstenose, thrombotischer Mikroangiopathie und anderen histologischen Erscheinungsformen der APS-Nephropathie, oft assoziiert mit renaler Hypertonie, manifestieren. Wichtig zur Differenzialdiagnose gegenüber der Lupusnephritis ist die histologische Abklärung, da das APS eine Antikoagulation und in der Regel keine Immunsuppression erfordert. Im Rahmen des Sjögren-Syndroms ist eine renale Manifestation mit 30–40% relativ häufig. Allerdings hat die typische Manifestation in Form der interstitiellen Nephritis mit distal tubulärer Azidose Typ 1 eine vergleichsweise geringe klinische Bedeutung und bedarf keiner Immunsuppression. Die renale Krise ist eine schwerwiegende Komplikation der systemischen Sklerose, hat jedoch seit Anwendung der ACE-Hemmer gegenüber pulmonaler Hypertonie und Lungenfibrose an prognostischer Bedeutung verloren. Wichtig für die Beherrschung der renalen Krise, welche sich histologisch in vaskulären Veränderungen manifestiert, ist die antihypertensive Therapie mit Hemmung des Renin-Angiotensin-Systems. Bei Polymyositis/Dermatomyositis sowie Sharp-Syndrom ist eine renale Manifestation bis auf die akute tubuläre Nekrose bei unzureichend behandelter Rhabdomyolyse eher selten. Da jedoch im Zusammenhang mit beiden Krankheitsbildern wie auch bei Sjögren-Syndrom und systemischer Sklerose in seltenen Fällen sekundäre Glomerulonephritiden vorkommen können, sollte im Hinblick auf die therapeutische Konsequenz im Zweifelsfall immer die histologische Abklärung durch Nierenbiopsie erfolgen.

Abstract

Renal manifestations of connective tissue diseases differ with respect to pathogenesis, frequency and consequences for prognosis and therapy. Lupus nephritis represents the prognostically most important organ manifestation of systemic lupus erythematosus (SLE) and needs histological evaluation by renal biopsy for optimal therapy. Low-dose cyclophosphamide pulse therapy in combination with glucocorticoids is the treatment of choice for remission induction of proliferative lupus nephritis. Azathioprin is used for maintenance of remission. In the case of side effects or ineffectiveness of standard therapy, mycophenolat mofetil (MMF) can be used for both remission induction and maintenance of remission. In refractory disease, B cell depletion by rituximab is promising. The renal manifestations of antiphospholipid syndrome (APS) include renal artery stenosis, thrombotic microangiopathy and other histological features of APS nephropathy often associated with renal hypertension. Especially in cases of secondary APS due to SLE, differentiation to lupus nephritis by renal biopsy is important with respect to the therapeutic consequences, anticoagulation in APS nephropathy and immunosuppression in lupus nephritis. Renal involvement in Sjögren's syndrome is observed in about 30–40%. The characteristic finding is interstitial nephritis with distal tubular acidosis type 1. This disease has a good prognosis with respect to renal function and needs no immunosuppression. Renal crisis is a severe complication of systemic sclerosis, but has lost the dominant prognostic importance in the disease course due to the use of ACE inhibitors in comparison to both pulmonary fibrosis and pulmonary hypertension. Antihypertensive therapy is critical in the management of scleroderma renal crisis which is mainly characterised by vascular changes and endothelial dysfunction. Despite the possibility of acute tubular necrosis due to rhabdomyolysis in cases of polymyositis and dermatomyositis, renal disease is relatively rare in patients with myositis as well as in those with mixed connective tissue disease (MCTD). On the other hand, rare cases of glomerulonephritis have been observed not only in patients with polymyositis, dermatomyositis and MCTD but also in those with Sjögren's syndrome and systemic sclerosis. Therefore, histological evaluation of kidney tissue should be done in connective tissue diseases with unclear renal affection with respect to differential therapy.

Schlüsselwörter

Kollagenosen - Nierenbeteiligung - Pathogenese - Therapie

Key words

connective tissue diseases - renal involvement - pathogenesis - therapy

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