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Background: Pregnancies in patients with complement gene variant-mediated thrombotic microangiopathy (cTMA) are challenging, and pregnancies in such patients after kidney transplantation (KTX) are even more so., Methods: We identified nine pregnancies following KTX of three genetically high-risk cTMA patients enrolled in the Vienna thrombotic microangiopathy cohort. Preventive plasma therapy was used in three pregnancies, and one patient had ongoing eculizumab (ECU) therapy during two pregnancies., Results: Seven out of nine pregnancies (78%) resulted in the delivery of healthy children. The other two included one early abortion at gestational Week 12 during ongoing ECU therapy and one late foetal death at gestational Week 33 + 3, most likely not related to complement dysregulation. Kidney transplant function after delivery remained stable in all but one pregnancy. In the aforementioned case, a severe cTMA flare occurred after delivery despite use of preventive plasma infusions. Kidney graft function could be rescued in this patient by ECU. As such, successful pregnancies can be accomplished in kidney transplant recipients (KTRs) with a history of cTMA. We used preemptive plasma therapy or ongoing ECU treatment in selected cases., Conclusions: Thus, becoming pregnant can be encouraged in KTRs with native kidney cTMA. Extensive preconception counselling, however, is mandatory in such cases., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: A novel data-driven cluster analysis identified distinct pathogenic patterns in C3-glomerulopathies and immune complex-mediated membranoproliferative glomerulonephritis. Our aim was to replicate these observations in an independent cohort and elucidate disease pathophysiology with detailed analysis of functional complement markers., Methods: A total of 92 patients with clinical, histological, complement and genetic data were involved in the study, and hierarchical cluster analysis was done by Ward method, where four clusters were generated., Results: High levels of sC5b-9 (soluble membrane attack complex), low serum C3 levels and young age at onset (13 years) were characteristic for Cluster 1 with a high prevalence of likely pathogenic variations (LPVs) and C3 nephritic factor, whereas for Cluster 2-which is not reliable because of the small number of cases-strong immunoglobulin G staining, low C3 levels and high prevalence of nephritic syndrome at disease onset were observed. Low plasma sC5b-9 levels, decreased C3 levels and high prevalence of LPV and sclerotic glomeruli were present in Cluster 3, and patients with late onset of the disease (median: 39.5 years) and near-normal C3 levels in Cluster 4. A significant difference was observed in the incidence of end-stage renal disease during follow-up between the different clusters. Patients in Clusters 3-4 had worse renal survival than patients in Clusters 1-2., Conclusions: Our results confirm the main findings of the original cluster analysis and indicate that the observed, distinct pathogenic patterns are replicated in our cohort. Further investigations are necessary to analyse the distinct biological and pathogenic processes in these patient groups., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA.)

Conditions presenting with signs of thrombotic microangiopathies (TMAs) comprise a wide spectrum of different diseases. While pathological hallmarks are thrombosis of arterioles and capillaries, clinical signs are mechanical haemolysis, thrombocytopenia and acute renal injury or neurological manifestations. The current classification of various syndromes of TMA is heterogeneous and often does not take the underlying pathophysiology into consideration. Therefore we propose a simplified classification based on the aetiology of different syndromes leading to TMA. We propose to categorize different TMA syndromes in hereditary and acquired forms and classify them based on the genetic background or underlying conditions. Of course, this classification is not always distinctly applicable in each case and from time to time reassessment of the established diagnosis is strongly recommended. The recommended treatment of TMA in the past was plasma exchange (PE). However, recently, the terminal complement inhibitor eculizumab became commercially available and has shown promising results in different open-label studies and case series. In our centre, first-line therapy is PE; however, patients are instantly switched to complement inhibitory therapy in case of treatment failure or intolerance.

Aims: The binary sign, a binary appearance of the left ventricular endocardial border, was suggested to be an echocardiographic hallmark in diagnosing Fabry disease, a hereditary, lysosomal storage disorder. The aim of the present study was to examine the reliability of the binary sign as a screening tool to identify patients with Fabry disease., Methods and Results: In total 309 subjects with an interventricular septum (IVS) thickness of ≥12 mm were investigated, of which 14 had a confirmed diagnosis of Fabry disease. Urinary globotriaosylceramide testing was used to rule out Fabry disease in the control group. From all patients echocardiographic images of the apical four-chamber view were analysed offline by a blinded observer. A binary sign was seen in 63 patients (20%), 4 had Fabry disease and 59 belonged to the control group. Although the proportion of binary signs in patients with Fabry disease was higher (29%) compared with the control group (20%) this difference was not statistically significant. The sensitivity and specificity were 28% (95% confidence interval (CI): 12-65%) and 80% (95% CI: 76-85%), respectively. In a logistic regression model adjusted for age, sex and presence of Fabry disease, the occurrence of a binary sign was highly dependent on the IVS thickness (odds ratio: 1.21; 95% CI: 1.1-1.35; P<0.001)., Conclusion: The endocardial binary appearance is associated with the degree of septal hypertrophy but cannot adequately distinguish between patients with Fabry disease and patients with other causes of left ventricular hypertrophy.