Drug-induced Glomerulonephritis: The Spectre of Biotherapeutic and Antisense Oligonucleotide Immune Activation in the Kidney:

Prevalence of immune-mediated glomerulonephritis has increased in preclinical toxicity studies, with more frequent use of biotherapeutic agents (especially antigenic humanized molecules) and antisense oligonucleotide (ASO) therapies. Immune complex disease affects a small number of study monkeys, often correlates with antidrug antibody (ADA) titers, and occurs at a dose that favors immune complex formation or impedes clearance. While preclinical glomerulonephritis often fails to correlate with evidence of glomerular or vascular injury in human clinical trials and is not considered predictive, additional animal investigative immunohistochemical work may be performed to substantiate evidence for immune complex pathogenesis. While ADA is most commonly encountered as a predisposing factor with biotherapeutic agents, complement activation may occur without circulating complexes, and other mechanisms of non-ADA immune-mediated glomerulonephritis have been observed including nonendogenous immune aggregates and i...