Immunoglobulin G4-related kidney disease: Pathogenesis, diagnosis, and treatment

Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized clinical entity that often involves multiple organs; it is characterized by high levels of serum immunoglobulin G4 (IgG4), dense infiltration of IgG4+ cells, and storiform fibrosis. Cellular immunity, particularly T cell-mediated immunity, has been implicated in the pathogenesis of IgG4-RD. The most frequent renal manifestations of IgG4-RD are IgG4-related tubulointerstitial nephritis, membranous glomerulonephropathy (MGN), and obstructive nephropathy secondary to urinary tract obstruction due to IgG4-related retroperitoneal fibrosis, prostatitis, or ureter inflammation. Kidney function impairment can be acute or chronic. In IgG4-MGN, proteinuria can be in the nephrotic range. The diagnosis of IgG4-related kidney disease should not be based solely on serum IgG4 levels or the number of tissue-infiltrating IgG4+ plasma cells. Diagnosis should be based on specific histopathological findings, confirmed by tissue immunostaining and an appropriate clinical context. Steroid treatment is the first-line therapy. For relapsing or refractory cases, immunosuppressants could be combined with steroids. In hydronephrosis patients, appropriate immunosuppressive therapy could preclude the implantation of a double J ureteral catheter.