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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 70 (1992), S. 865-874 
    ISSN: 1432-1440
    Keywords: Glomerular mesangium ; Glomerulonephritis ; Glomerulosclerosis ; Integrins ; Cytokines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Mesangial cells play an important role in the development and progression of human glomerular disease. This article summarizes some important aspects of mesangial properties and behaviour in situ. Intrinsic mesangial cells express α-smooth muscle actin and are best characterized as myofibroblasts or glomerular pericytes. The main intergin receptor in the mesangium is the α1\1 integrin. The \2 and \3 integrins have not been detected. Mesangial cells in situ fail to react with many monoclonal antibodies which stain human mesangial cells in culture, including leukocyte activation antigens. Prominent reactions in glomerular disease are mesangial expansion and progressive glomerular sclerosis, which are preceded by or associated with mesangial cell hypertrophy and/or proliferation. Mesangial enlargement is accompanied by an altered integrin expression and an abnormal composition of extracellular mesangial matrix. From the numerous autocrine and paracrine mediators identified in vitro which stimulate or inhibit mesangial cell growth and extracellular matrix synthesis, up to now only a few factors have been shown to be present in selected human glomerulopathies. These include platelet derived growth factors and platelet derived growth factor receptor β, transforming growth factors \, interleukin 1β, tumor necrosis factor α, and interleukin 6. Further identification of such mediators in situ will improve our understanding of pathological glomerular processes, particularly with respect to the multifunctional properties of the mesangial cell.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 63 (1985), S. 978-987 
    ISSN: 1432-1440
    Keywords: Glomerulonephritis ; Extramembraneous glomerulonephritis ; Membranoproliferative glomerulonephritis ; Lupus erythematosus ; Steroids ; Antiplatelet agents ; Glomerulonephritis ; Extramembranöse Glomerulonephritis ; Membranoproliferative Glomerulonephritis ; Lupus erythematodes ; Steroide ; Plättchenhemmer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Das Thema der therapeutischen Beeinflussung der entzündlichen Pathomechanismen bei chronisch-idiopathischer Glomerulonephritis bedarf einiger kritischer Anmerkungen. Eine ätiologische Behandlung ist nur in Ausnahmefällen möglich (infektiöse Tropenkrankheiten, infizierter ventrikuloatrialer Shunt etc.). Einer erfolgreichen Beeinflussung der Pathomechanismen, welche die glomeruläre Entzündung auslösen und unterhalten, steht unsere Unkenntnis über die im einzelnen verantwortlichen Schritte entgegen. Neuere Untersuchungen legen Schlüsselrollen für die terminale Komponente des Komplementsystems, Produkte des Lipoxygenaseabbauweges der Arachidonsäure sowie Sauerstoffradikale nahe, welche therapeutisch nicht oder nur beschränkt beeinflußbar sind. Ferner beruht die Progredienz glomerulärer Entzündungen in die Niereninsuffizienz in der Regel auf fortschreitender Sklerosierung von Glomerulus, Gefäßen und Interstitium und nicht auf zunehmenden aktiv entzündlichen glomerulären Läsionen. Beispielhaft wurden bei der Sichtung der veröffentlichten kontrollierten Therapiestudien die Untersuchungen bei extramembranöser und membranoproliferativer Glomerulonephritis herausgegriffen. Hierbei wurde eine im Ausmaß nur beschränkte, und nicht in allen Studien gesicherte, Beeinflussung der Nierenfunktion gefunden, der andererseits erhebliche Nebenwirkungen gegenüberstehen. Eine abschließende Wertung kommt zu dem Urteil, daß eine medikamentöse Beeinflussung der entzündlichen Pathomechanismen fragwürdig ist, daß jedoch ein therapeutischer Nihilismus nicht angezeigt ist angesichts der Beeinflußbarkeit unspezifischer Schädigungsmechanismen (antihypertensive Behandlung, diätetische Intervention).
    Notes: Summary It is controversial whether the pathomechanisms involved in chronic idiopathic glomerulonephritis are susceptible to therapeutic intervention. Etiological therapy, i.e. elimintion of the responsible antigen, is possible only in exceptional cases, e.g. tropical diseases, infected ventriculoatrial shunt etc. Antiinflammatory therapy directed against pathomechanisms initiating or maintaining glomerular inflammation has an uncertain theoretical foundation because of lack of knowledge relating to the exact steps mediating tissue injury. Recent studies suggest keyroles for terminal components of complement system, products of lipoxygenase pathway of arachidonic acid and oxygen radicals — all of which are not readily influenced by available therapeutic modulaties. Finally, progression of glomerular inflammation to renal failure is usually not the cause of cumulative acute inflammatory glomerular lesions but rather the consequence of progressive sclerosis of glomeruli, arterioles and interstitium. As examples of controlled intervention trials, studies on extramembranous and membranoproliferative glomerulonephritis are discussed. The studies show limited and not always statistically significant influence on renal function, however, at the expense of considerable side effects. It is concluded that it is highly questionable whether inflammatory pathomechanisms are influenced by currently available drugs. However, therapeutic nihilism is not appropriate given modalities to influence mechanisms of nonspecific damage, e.g. by antihypertensive medication or dietary intervention.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric nephrology 13 (1999), S. 816-823 
    ISSN: 1432-198X
    Keywords: Key words Schönlein-Henoch purpura ; Glomerulonephritis ; Hypertension ; Proteinuria ; Renal failure ; Plasma exchange
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We studied the long-term outcome of 64 children with biopsy-proven Schönlein-Henoch purpura (SHP) nephritis over 1–23 years of follow-up. Overall renal survival 10 years after onset was 73%. Multivariate logistic regression analysis identified initial renal insufficiency (P=0.004), nephrotic syndrome (P=0.037), and the severity of histological alterations, as defined by the proportion of glomerular crescents (P=0.051), as significant independent predictors of progressive renal failure. Four patients followed for more than 19 years showed glomerular damage after transient recovery. Eight children with crescentic nephritis associated with a rapidly progressive course and/or persistent nephrotic syndrome were treated by at least seven sessions of plasma exchange (PE) within 16 weeks of onset of purpura. During treatment serum creatinine levels dropped in each patient from a mean of 2.3 to 1.1 mg/dl, followed by a rebound increase. Repeated courses of PE in 5 patients produced comparable responses. Four patients undergoing PE reached end-stage renal disease at 1.2.–3.7 years after onset, whilst 3 finally were in preterminal renal failure (creatinine 3.2–6.1 mg/dl after 7–13.5 years), and 1 patient reached a normal glomerular filtration rate. Our experience suggests that initial renal insufficiency is the best single predictor of the further clinical course in children with SHP nephritis. Early PE appears to delay the progression in some patients with severe, rapidly progressive forms of the disease.
    Type of Medium: Electronic Resource
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