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Aktuelle Rheumatologie 2020; 45(02): 150-162
DOI: 10.1055/a-1117-2920
Übersichtsarbeit
© Georg Thieme Verlag KG Stuttgart · New York

Nierenbeteiligung bei Kollagenosen – Teil 1: Lupus-Nephritis

Renal Involvement in Connective Tissue Diseases – part 1: Lupus Nephritis
Peter Oelzner
1   Klinik für Innere Medizin III, Universitätsklinikum Jena
,
Kerstin Amann
2   Abteilung Nephropathologie, Universitätsklinikum Erlangen
,
Gunter Wolf
3   Nephrologie, Klinik für Innere Medizin III, Universitätsklinikum Jena
› Author Affiliations
Further Information

Publication History

Publication Date:
02 April 2020 (online)

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Zusammenfassung

Die Lupus-Nephritis (LN) tritt in Abhängigkeit von Ethnizität und Geschlecht in bis zu 50% der Patienten mit systemischem Lupus erythematodes (SLE) auf und ist die prognostisch entscheidende Organmanifestation bei SLE. Pathogenetisch wichtige Aspekte des SLE sind eine multifaktoriell bedingte Störung der Clearance von im Rahmen von Apoptose und NETose anfallendem Autoantigen, was in der Entwicklung einer Autoimmunreaktion resultiert, eine Amplifizierung der pathologischen Immunreaktion durch eine Überaktivierung des Typ-I-Interferon-Signalweges und eine Zytokinimbalance. An der Niere manifestiert sich der pathogenetische Prozess in Form einer Immunkomplexglomerulonephritis. Entscheidend für die Prognose der LN sind frühzeitige Diagnose und umgehende Therapieeinleitung. Die Auswahl der medikamentösen Therapie basiert grundsätzlich auf dem Befund der Nierenbiopsie. Bei Vorliegen einer proliferativen LN (Klasse III und IV, auch in Kombination mit einer membranösen LN) erfolgt eine Remissionsinduktion mit einer intravenösen low-dose Cyclophosphamid (CYC) – Therapie (6 x 500 mg) oder mit Mycophenolatmofetil (MMF) kombiniert mit initial hoch dosierten Glukokortikoiden (GK), gefolgt von einer Remissionserhaltung mit Azathioprin oder MMF. Bei Therapie-refraktärer Situation erfolgt der Wechsel von CYC auf MMF oder umgekehrt. Alternativ können auch Rituximab oder Calcineurin-Inhibitoren eingesetzt werden. Bei anderen Formen der LN wird das therapeutische Vorgehen wesentlich durch die Entwicklung der Nierenfunktion und das Ausmaß der Proteinurie bestimmt. Zusätzlich kommen supportive Massnahmen, wie der generelle Einsatz von Hydroxychloroquin, ACE-Hemmer oder Angiotensin-Rezeptor-Blocker in Abhängigkeit vom Ausmaß der Proteinurie und vom Blutdruck, sowie Maßnahmen zur Thromboembolie-, Osteoporose- und Infektionsprophylaxe zur Anwendung.

Ziele der Therapie sind eine möglichst komplette renale Remission, die Vermeidung chronischer Schäden und eine effektive Reduktion von GK. Eine komplette Remission, welche sich über den Erhalt einer normalen Nierenfunktion und eine effektive Reduktion der Proteinurie definiert, wird in ca. 50–60% erreicht. Dies unterstreicht einerseits die Effektivität der aktuellen Therapie, beleuchtet aber auch die Notwendigkeit neuer Therapiestrategien, gerade auch in Anbetracht der hohen Rate chronischer Schäden.

Neue therapeutische Ansätze wie Multitarget-Therapie und neue Protokolle zur B-Zell-Depletion und -Neutralisation sowie weitgehend GK-freie Behandlungsprinzipien zielen auf eine noch effektivere und Nebenwirkungs-ärmere Therapie der LN.

Abstract

Lupus nephritis (LN) occurs dependent on ethnicity and gender in up to 50% of patients with systemic lupus erythematosus (SLE) and represents the prognostic most important organ manifestation in SLE. Pathogenetic important aspects of SLE are a multifactorial caused disturbance of the clearance of autoantigen released in the context of apoptosis and NETosis resulting in the development of autoimmune reaction, an amplification of the pathologic immune reaction by hyperactivation of type I-interferon signaling and cytokine imbalance. The pathogenetic process in the kidney results in immune complex glomerulonephritis.

Early diagnosis and initiation of therapy are of critical importance for the prognosis of LN. The selection of therapy is based principally on the findings in renal biopsy. In the case of proliferative LN (class III or IV, also in combination with membranous LN) a remission induction with low-dose cyclophosphamide (CYC)-pulse therapy (6 x 500 mg) or with mycophenolatofetil (MMF) in combination with initial high dose glucocorticoids (GC) is followed by a maintenance therapy with azathioprine or MMF. In refractory situations a switch from CYC to MMF or conversely is indicated. Alternatively rituximab or calcineurin inhibitors can also be used. In other forms of LN the therapeutic procedure is essentially determinated by the course of renal function and the extent of proteinuria. In addition supportive procedures such as the general use of hydroxychloroquine, ACE inhibitors or angiotensin rezeptor blockers in dependence of the extent of proteinuria and of blood pressure and prophylactic measures to prevent thromboembolism, osteoporosis and infections come into use. Aims of therapy are a preferably complete renal remission, prevention of chronic damage and an effective reduction of GC dose. A complete remission which is defined by the preservation of normal renal function and a substantial reduction of proteinuria is achieved in approximately 50–60%. This underlines the effectiveness of the curent therapy on one hand but illuminates the need of new therapeutic strategies on the other, especially in view of the high rate of damage.

New therapeutic approaches such multitarget therapy, new protocolls of B cell depletion and B cell neutralization and GC free treatment principles aim at a more effective and side effect poor therapy of LN.

Schlüsselwörter

Lupus-Nephritis - Pathogenese - Therapie

Key words

Lupus nephritis - pathogenesis - therapy
 

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