👤 Syed J Mehdi

In recent years, there has been an emergence of new antigens discovered in membranous nephropathy (MN). Whether these antigens have impacted the approach to, and management of, MN patients undertaken by nephrologists is still unclear. We conducted a cross-sectional international survey pertaining to 13 antigens recently discovered in MN. The survey was distributed by the National Kidney Foundation, direct emails, and social media. PLA2R, THSD7A, NELL1, and EXT1/2 testing were readily available while the most common response for other antigen testing was 'Not Performed' or 'Unknown'. All respondents had tested for or treated PLA2R-positive MN. Of 79 respondents, only 12.7% had treated THSD7A, 15.2% for NELL1 and 6.3% for EXT1/2 positive MN. For PLA2R, THSD7A, and NELL1, a majority chose rituximab (75.4, 87.5, and 80.0%, respectively) as initial treatment, and would treat with immunosuppression before completing 6 months of conservative therapy. A majority of respondents would routinely or occasionally omit a kidney biopsy in the setting of positive serum anti-PLA2R antibodies, however, 27.5% would rarely do so. There was no clear consensus across respondents regarding the use of anti-PLA2R serum levels in determining remission. Although many new MN antigens have been discovered, there is limited availability of tests identifying these less common antigens. While the survey suggests potential for utilization of an antigen-tailored approach based on identified differences in screening and treatment practices, there remains a lag in the full adoption of this new information. Further progress in accessibility of antigen testing and research into antigen associations will enable a more individualized approach to the management of MN. Show less

Extracranial arteriovenous malformations (eAVMs) are complex vascular lesions characterized by anomalous arteriovenous connections, vascular instability, and disruptions in endothelial cell (EC)-to-mural cell (MC) interactions. This study sought to determine whether eAVM-MCs could induce endothelial-to-mesenchymal transition (EndMT), a process known to disrupt vascular integrity, in the eAVM microenvironment. eAVM and paired control tissues were analyzed using RT-PCR for EC ( Show less

Heart failure is a leading cause of mortality in South Asians. However, its genetic etiology remains largely unknown. Cardiomyopathies due to sarcomeric mutations are a major monogenic cause for heart failure (MIM600958). Here, we describe a deletion of 25 bp in the gene encoding cardiac myosin binding protein C (MYBPC3) that is associated with heritable cardiomyopathies and an increased risk of heart failure in Indian populations (initial study OR = 5.3 (95% CI = 2.3-13), P = 2 x 10(-6); replication study OR = 8.59 (3.19-25.05), P = 3 x 10(-8); combined OR = 6.99 (3.68-13.57), P = 4 x 10(-11)) and that disrupts cardiomyocyte structure in vitro. Its prevalence was found to be high (approximately 4%) in populations of Indian subcontinental ancestry. The finding of a common risk factor implicated in South Asian subjects with cardiomyopathy will help in identifying and counseling individuals predisposed to cardiac diseases in this region. Show less