Mechanisms of glomerular disease

Abstract

Glomerular diseases, clinically manifesting with proteinuria, hematuria, or azotemia, result from complex disease processes. This complexity is driven by an individual's genome, unique environmental exposures, and, importantly, through their interaction mediated by innate and adaptive immune responses. The astonishing complexity of each of these aspects is emerging through the lens of new technologies that provide the ability to interrogate human biosamples, including kidney biopsies, in exquisite molecular detail. An individual's genetic background, their immune responses, and environmental exposures interactively contribute to disease pathogenesis to shape complex disease phenotypes such as glomerulonephritis. In this chapter we review the general pathogenic mechanisms that drive multiple glomerular disease diagnoses and have selected a few specific examples to illustrate how these pathogenic mechanisms influence disease initiation or progression.We have divided the disease mechanisms into the general domains of genetics and innate and adaptive immunity and highlight how genetic background modifies the immune response to cause glomerular diseases in susceptible individuals.