Proteinuria is accompanied by intratubular complement activation and apical membrane deposition of C3dg and C5b-9 in kidney transplant recipients
Gustaf Lissel Isaksson, Marie Bodilsen Nielsen, Gitte R. Hinrichs, Nicoline V. Krogstrup, Rikke Zachar, Heidi Stubmark, Per Svenningsen, Kirsten Madsen, Claus Bistrup, Bente Jespersen, The CONTEXT Study Group, Henrik Birn, Yaseelan Palarasah, Boye L. Jensen
Abstract
The present study proposes a mechanistic coupling between proteinuria and aberrant filtration of complement precursors, intratubular complement activation, and apical membrane attack in kidney transplant recipients. C3dg and C5b-9-associated C9 neoantigen associate with proximal tubular apical membranes as demonstrated in urine extracellular vesicles. The discovery suggests intratubular complement as a mediator between proteinuria and progressive kidney damage. Inhibitors of soluble and/or luminal complement activation with access to the tubular lumen may be beneficial.