Immunoglobulin G4-related kidney diseases: An updated review

Abstract

This review will encompass definition, pathogenesis, renal clinical manifestations and treatment of immunoglobulin G4-related diseases (IgG4-RDs). IgG4-RD is a recently recognized clinical entity that often involves multiple organs and is characterized by high levels of serum immunoglobulins G4, dense infiltration of IgG4⁺ cells and storiform fibrosis. Cellular immunity, particularly T-cell mediated immunity, has been implicated in the pathogenesis of IgG4-RDs. The most frequent renal manifestations of IgG4-RD are IgG4-related tubulointerstitial nephritis, membranous glomerulopathy and obstructive nephropathy secondary to urinary tract obstruction due to IgG4-related retroperitoneal fibrosis. IgG4-RD diagnosis should be based on specific histopathological findings, confirmed by tissue immunostaining, typical radiological findings and an appropriate clinical context. The first line treatment is the steroids with two warnings: Steroid resistance and relapse after discontinuation. In the case of steroid resistance, B cell depleting agents as rituximab represent the second-line treatment. In the case of relapse after discontinuation, steroid treatment may be associated with steroid sparing agents. Since the disease has been only recently identified, more prospective, long-term studies are needed to an improved understanding and a more correct and safe treatment.

Keywords: B cell depleting agents; Immunoglobulin G4-related disease; Lymphoplasmacytic infiltration; Steroid treatment; Storiform fibrosis; Tubulointerstitial nephritis.

Figure 1

Pathogenesis of immunoglobulin G4-related disease. CTL-4: Cytotoxic T-lymphocyte-associated antigen 4; FcR-3: Fc receptor like 3; TNFα: Tumor necrosis factor alpha; NODR: Nucleotide-activating factor belonging to the tumor necrosis factor (TNF) family; TLR2: Toll-like receptor 2; BAFF: B cell activating factor; APRIL: A proliferative-inducing ligand; TGFβ: Tumor growth factor beta.