Afschin Soleiman

Background Physicians refer proteinuric patients to kidney biopsy in order to clarify the issue of underlying renal disease. We compared kidney biopsy results with classical outcome parameters in a large cohort of patients with biopsy proven glomerulonephritis (GN). Methods In a retrospective analysis, 2687 patients with different forms of GN from 123 Austrian centres were investigated. Patient characteristics, the diagnosis of GN and its respective subtype and clinical symptoms such as arterial hypertension, haematuria, amount of proteinuria and estimated glomerular filtration rate (eGFR) were tested for their association with all‐cause mortality and progression to end‐stage renal disease (ESRD). Results During a median follow‐up of 129·9 months (IQR 89·6; 177·7), 688 patients (25·6%) died and 718 patients required dialysis (29·4%). In multivariate Cox's regression analysis age (HR 1·06), female sex (HR 0·71), eGFR (HR 0·74), the diagnosis of GN and its subtypes predicted patient survival (all P < 0·01), whereas the amount of proteinuria was not associated with patient survival. The incidence of progression to ESRD was associated with female sex (HR 0·71), eGFR (HR 0·65), amount of proteinuria (HR 1·15) and the diagnosis of GN and its subtypes (all P < 0·01). Nephrotic or nephritic syndromes were not associated with patient survival or progression to ESRD and did not add further predictive value to outcome of GN. Conclusions Our study demonstrates histological diagnosis of GN and its specific subtype predicts patient survival and dialysis incidence. Therefore, kidney biopsy should be an integral part of routine diagnostic assessment in patients with any forms of suspected GN.

This prospective pilot study was performed to elucidate whether early changes in serum levels of the Her-2/neu extracellular domain (ECD) reflect histopathological response to trastuzumab-based neoadjuvant therapy in patients with Her-2/neu-overexpressing breast cancer. ECD levels were measured throughout neoadjuvant trastuzumab-based treatment in 16 patients using a Her-2/neu Microtiter ELISA. In 9 (56%) patients with Her-2/neu shedding tumors (ECD > 15 ng/ml), ECD values (in % of baseline) of non-responders vs. responders were 117% vs. 55% on day 8 (p=0.014), 157% vs. 58% on day 22 (p=0.061) and 114% vs. 46% at restaging (p=0.049). Serial monitoring of serum Her-2/neu ECD levels may represent a valuable tool to predict pathological response to trastuzumab-based neoadjuvant therapy in patients with Her-2/neu-overexpressing tumors.

Morbus Wegener ist eine vor allem kleinste Gefäße betreffende nekrotisierende Vaskulitis, die zu einer erheblichen Funktionsbe einträchtigung der beteiligten Organsysteme führt und hauptsächlich in den Nieren und im Respirationstrakt manifest wird. Die übliche Therapie basiert auf längerfristiger Immunsuppression bestehend aus einer Kombination von Kortikosteroiden. Cyclophosphamid, Azathioprin oder Methotraxat. Tödliche Verläufe sind oft Folge von Rezidiven oder mangelndem Ansprechen auf diese Therapie. Wie bei vielen chronisch entzündlichen Erkrankungen beeinflusst der Tumornekrosefaktor (TNF) wesentlich das Voranschreiten der Erkrankung. Wir berichten über einen Patienten mit massiver orbitaler Morbus Wegener Manifestation, der unter maximaler Cyclophosphamid- und Kortikosteroidtherapie ein akutes Nierenversagen entwickelte. Um eine weitere Progression zu verhindern, wurde ihm über sechs Monate hinweg der TNF-Antikörper Infliximab^® in einer Dosis von 3 mg/kg Körpergewicht sechs mal verabreicht. Zusätzlich wurde in dieser Zeit die Therapie mit Kortikosteroiden und Cyclophosphamid fortgesetzt, wobei letzteres nach drei Monaten durch Azathioprin ersetzt wurde. Bere its die erste Infliximab^®-Infusion führte zu einer Verbesserung der Nierenfunktion, eine Entwicklung, welche die gesamte Therapie hindurch anhielt. Die MDRD-GFR (Modification of Diet in Renal Disease — Glomerular Filtration Rate) stieg von 15,3 ml/min/1,73 m² vor der ersten auf 55,5 ml/min/1,73 m² nach der letzten Infusion. Die Serumkreatininkonzentration und die Proteinurie verminderten sich ebenso wie die cANCA Titer. Ohne Auftreten von Nebenwirkungen wurde duch die TNF-Blockade eine klinische Remission erzielt. Eine erneut auftretende Entzündung der Orbita wurde durch eine erhöhte Dosis Azathioprin erfolgreich behandelt. Bei diesem Fall eines therapierefraktären Morbus Wegener stellte der Einsatz des monklonalen TNF-Antikörpers Infliximab^® ein wirksames Mittel zur Induktion einer klinischen Remission mit Wiederherstellung der Nierenfunktion dar. Wegener’s granulomatosis is a systemic necrotising vasculitis of small vessels that leads to severe impairment of affected organ systems. Conventional treatment is based on immunosuppression with a combination of steroids, cyclophosphamide, azathioprine or methotrexate over a prolonged time course. Early recurrence or disease refractory to therapy often results in a fatal outcome. As in other inflammatory disorders, tumor necrosis factor (TNF) plays an early and crucial role in progression of disease activity. We report on a patient with severe orbital Wegener’s granulomatosis who developed acute renal failure despite intense conventional immunosuppression with cyclophosphamide and steroids. To stop vasculitic activity, by disrupting the autoimmune inflammatory cascade, a TNF-blocking antibody (Infliximab^ŗ) was administered six times in a six-month period at 3 mg/kg body weight. Conventional immunosuppressive therapy with steroids and cyclophosphamide was continued, the latter being changed to azathioprine after three months. The first infusion of TNF antibody induced improvement of renal function, which continued throughout the course of therapy. The modification of diet in renal disease-glomerular filtration rate (MDRD-GFR) increased from 15.3 ml/min/1.73m² before the start of TNF-blockade to 55.5ml/min/1.73m² after six months of therapy. Serum creatinine levels, proteinuria and cANCA titer decreased concomitantly. Clinical remission of Wegener’s granulomatosis was induced without any major adverse events. A slight flare of orbital inflammation was successfully treated with an increased dose of azathioprine. Thus, in this case of refractory Wegener’s granulomatosis TNF-blockade by monoclonal chimeric TNF-antibody (Infliximab^ŗ) served as an effective tool to rescue kidney function and induce clinical remission.

Rapamycin is a new immunosuppressive agent approved for maintenance therapy after kidney transplantation. It may allow calcineurin-inhibitor-free, non-nephrotoxic immunosuppression. We report, however, on four kidney-transplant recipients who developed post-transplantation glomerulonephritis after conversion from a calcineurin-inhibitor-based immunosuppression to rapamycin. In all four patients nephrotic-range proteinuria occurred 2-9 months after conversion to rapamycin. Renal biopsy confirmed membrano-proliferative glomerulonephritis type 1 in one case, membranous glomerulonephritis in another and IgA-nephropathy in two cases, respectively. Calcineurin-inhibitor-based immunosuppression was reintroduced and resulted in complete remission of proteinuria and in stabilised renal function in all patients. We conclude that in the case of rapamycin-associated post-transplantation glomerulonephritis an attempt should be made to replace rapamycin by a calcineurin inhibitor.