IgG4-related kidney disease: from renal histopathology and immunopathogenesis to novel pharmacological interventions

Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a rare and chronic fibroinflammatory condition hallmarked by tumefactive lesions that can affect nearly any organ of the body and lead to fibrotic organ destruction. Parenchymal and non-parenchymal affection of the kidney and urogenital tract are subsumed under the umbrella term IgG4-related kidney disease (IgG4-RKD), which is a severe and quite common organ manifestation in IgG4-RD. The immunopathogenesis in IgG4-RD is depicted by a complex interplay of distinct B- and T-cell subsets, excessive antibody production, a unique cytokine environment and the development of exuberant fibrosis. Scientific advancements over the last two decades have fostered to explore a broad repertoire of pharmacological interventions starting from B-cell depleting agents and extending to modulators of T-cell co-stimulation.

The aim of this review is to a) provide an overview of the current knowledge on IgG4-RKD with an emphasis on the unique properties of renal histopathology and immunopathogenesis and b) overview novel pharmacological interventions targeting B cells, T cells, and beyond.

Speculating on a potential scenario that dominates IgG4-RD's treatment reality in 5 years, the advent of integrative treatment strategies combining both B- and T-cell targeting agents is conceivable.