C3d-Targeted factor H inhibits tissue complement in disease models and reduces glomerular injury without affecting circulating complement.

Complement-mediated diseases can be treated using systemic inhibitors. However, complement components are abundant in circulation, affecting systemic inhibitors' exposure and efficacy. Furthermore, because of complement's essential role in immunity, systemic treatments raise infection risk in patients. To address these challenges, we developed antibody fusion proteins combining the alternative-pathway complement inhibitor factor H (fH1-5) with an anti-C3d monoclonal antibody (C3d-mAb-2fH). Because C3d is deposited at sites of complement activity, this molecule localizes to tissue complement while minimizing circulating complement engagement. These fusion proteins bind to deposited complement in diseased human skin sections and localize to activated complement in a primate skin injury model. We further explored the pharmacology of C3d-mAb-2fH proteins in rodent models with robust tissue complement activation. Doses of C3d-mAb-2fH >1 mg/kg achieved >75% tissue complement inhibition in mouse and rat injury models while avoiding circulating complement blockade. Glomerular-specific complement inhibition reduced proteinuria and preserved podocyte foot-process architecture in rat membranous nephropathy, indicating disease-modifying efficacy. These data indicate that targeting local tissue complement results in durable and efficacious complement blockade in skin and kidney while avoiding systemic inhibition, suggesting broad applicability of this approach in treating a range of complement-mediated diseases.

Kidney Pathology Education for Nephrology Fellows: Past, Present, and Future.

Kidney pathology education is a critical component in training of nephrology fellows, as well as for continuing medical education for practicing nephrologists. Kidney pathology images are included on nephrology fellow board exams, and clinicopathologic correlation of kidney biopsy findings is critical in everyday clinical practice. Nephropathology training is a requirement by the American College of Graduate Medical Education within nephrology fellowship curricula. However, greater than one-third of fellowship program directors believe that nephropathology training for their fellows is not sufficient. During the Coronavirus Disease-19 pandemic, the use of digital learning has become commonplace with virtual conferences (local, national, and international) and online meetings becoming the norm for education. Nephrology has become a leader in free open-access online medical education, both prior to and, to even a greater extent, during the pandemic. Here, we review available resources to nephrology fellows and other learners to supplement nephropathology training, which includes medical blogs, journal clubs, interactive quizzes and games, online conferences, podcasts, and mentorship opportunities. These resources are archived and provide durable content to learners of all stages of training, even beyond the pandemic.