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Connective tissue diseases (CTD) comprise a group of inflammatory systemic diseases that can affect various organs. Kidney involvement is frequently associated with significant irreversible damage and often before patients become symptomatic. Screening tests of blood and urine as well as clinical vigilance are therefore essential for all CTDs with possible renal involvement. A kidney biopsy is the gold standard for the diagnosis, prognosis and treatment decisions. A common and severe organ involvement in systemic lupus erythematosus (SLE) is glomerulonephritis (GN), also collectively referred to as lupus nephritis (LN). If left untreated LN often leads to end-stage renal failure. The treatment depends on the clinical parameters and histopathology of the renal involvement. Mycophenolate mofetil and cyclophosphamide are potent but nonspecific immunosuppressants which have been available for many years. Recently, new substances specific for LN have also been approved for the first time. Kidney involvement in Sjogren's syndrome has been far less studied. In studies the frequency of renal involvement is still unclear and ranges from 5% to 33%. Tubulointerstitial nephritis (IN) is the typical form of renal involvement which clearly differs from GN in its clinical presentation. Recommendations for treatment are based exclusively on retrospective studies. A renal crisis in systemic scleroderma (SSc) is a rare but feared complication with a high mortality. An antiphospholipid syndrome (APS) nephropathy (APSN) can occur during CTD. These entities are vasculopathies and often thrombotic microangiopathies, which clearly differ from GN and IN in terms of pathophysiology, clinical features and treatment. This article provides an overview of the diversity of the most important renal manifestations of CTDs.Kollagenosen umfassen eine Gruppe entzündlicher Systemerkrankungen, die sich an unterschiedlichen Organen manifestieren können. Eine Beteiligung der Nieren geht häufig mit einem beträchtlichen, irreversiblen Schaden einher, oftmals bevor Patient:innen symptomatisch werden. Screeninguntersuchungen von Blut und Urin sowie klinische Wachsamkeit sind daher bei allen Kollagenosen mit möglicher renaler Beteiligung unabdingbar. Für Diagnose, Prognose und Therapieentscheidung ist eine Nierenbiopsie der Goldstandard. Eine häufige und schwere Organbeteiligung des systemischen Lupus erythematodes (SLE) sind Glomerulonephritiden (GNs), die kollektiv als Lupusnephritis (LN) bezeichnet werden. Unbehandelt führt die LN nicht selten zur terminalen Niereninsuffizienz. Die Therapie richtet sich nach Klinik und Histopathologie der Nierenbeteiligung. Mit Mycophenolat-Mofetil und Cyclophosphamid stehen seit vielen Jahren potente, aber unspezifische Immunsuppressiva zur Verfügung. Seit Kurzem sind zudem erstmals neue Substanzen speziell für die LN zugelassen worden. Die Nierenbeteiligung des Sjögren-Syndroms ist weit weniger untersucht. Die Häufigkeit ist letztlich unklar und reicht in Studien von 5–33 %. Meist kommt es zu einer tubulointerstitiellen Nephritis (IN), die sich in der klinischen Präsentation deutlich von den GNs unterscheidet. Die Therapieempfehlungen basieren ausschließlich auf retrospektiven Studien. Die renale Krise bei der systemischen Sklerose (SSc) ist eine seltene, aber gefürchtete Komplikation mit hoher Mortalität. Die Antiphospholipidsyndrom(APS)-Nephropathie (APSN) kann bei primärem oder sekundärem APS im Rahmen einer Kollagenose auftreten. Als Vaskulopathien bzw. thrombotische Mikroangiopathien unterscheiden sich beide Entitäten bezüglich Pathophysiologie, Klinik und Therapie deutlich von GN und IN. Diese Arbeit soll eine Übersicht über die Diversität der wichtigsten renalen Manifestationen bei Kollagenosen liefern.

Systemic lupus erythematosus (SLE) is a common autoimmune disorder with a complex and poorly understood immuno-pathogenesis. Lupus nephritis (LN) is a frequent and difficult to treat complication, which causes high morbidity and mortality. The multifunctional cytokine amphiregulin (AREG) has been implicated in SLE pathogenesis, but its function in LN currently remains unknown. We thus studied the model of pristane-induced LN and found increasing renal and systemic AREG expression during the course of disease. Importantly, renal injury was significantly aggravated in the absence of AREG, revealing a net anti-inflammatory role. Analyses of immune responses showed dual effects. On the one hand, AREG enhanced activation of pro-inflammatory myeloid cells, which however did not play a major role for the course of LN. More importantly, on the other hand, AREG strongly suppressed pathogenic cytokine production by T helper effector cells. This effect was more general in nature and could be reproduced in response to antigen immunization. Since AREG has been postulated to downregulate T cell responses via enhancing Treg suppressive capacity, we followed up on this aspect. Interestingly, however, in vitro studies revealed potential direct and Treg independent effects of AREG on T helper effector cells. In favor of this notion, we found significantly enhanced T cell responses and consecutive aggravation of LN, only if epidermal growth factor receptor (EGFR) signaling was abrogated in total T cells, but not if the EGFR was absent on Tregs alone. Finally, we also found enhanced AREG expression in plasma and renal biopsies of patients with LN, supporting the relevance of our findings for human disease. In summary, our data identify AREG as an anti-inflammatory mediator of LN via broad downregulation of pathogenic T cell immunity. These findings further highlight the AREG/EGFR axis as a potential therapeutic target.

The purpose of this observational, multi-center study was to reveal epidemiologic, etiological and clinical aspects of hospitalized children with thermal injuries in Germany and Austria and the workup of a renewed web-based pediatric burn registry.From 2006 to 2015, comprehensive patient data of thermally injured children in Germany and Austria were collected prospectively. Retrospective analysis of age, gender, mechanism of injury, total body surface area burned, way of admission and length of stay was performed, followed by the comparative analysis between designated burn centers and other pediatric hospitals.32 hospitals participated in the study including data of 13,460 thermally injured hospitalized children. The majority was 12-36 months of age with a share of 48%. 56.5% were boys. The most frequent cause of injury was scalding representing 74.4%. Designated pediatric burn centers treated 82.2% of all patients. In relation to non-centers, no significant differences were seen concerning the affected total body surface area and the amount of patients1 year of age in contrast to a significant difference regarding the amount of fire injuries, all being parameters indicating the severity of thermal injuries. Overall mortality was 0.1%.This study extends our knowledge about population characterization of thermally injured children, highlights risk factors and serves as a basis for the renewed pediatric burn registry from 2016 on.