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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Korrespondenzadresse
Prof. Dr. Peter Oelzner
Medizinische Klinik III
Friedrich-Schiller-Universität
Jena
Funktionsbereich
Rheumatologie und Osteologie
Erlanger Allee 101
07740 Jena
Phone: +49/3641/932 43 26
Fax: +49/3641/932 68 42
Email: Peter.Oelzner@med.uni-jena.de
