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.

Steroid Therapy and Steroid Response in Autoimmune Pancreatitis

“…A group of extrapancreatic lesions, including dacryoadenitis, sialoadenitis [103], hilar lymphadenopathy [88], interstitial pneumonitis [104], sclerosing cholangitis [21,35,54], retroperitoneal fibrosis [105], and tubulointerstitial nephritis [106], are thought to have a close association with type 1 AIP, whereas inflammatory bowel diseases (e.g., ulcerative colitis and Crohn's disease) are associated with type 2 AIP [2,4,12,14,21]. Another group categorized as possible AIP-associated lesions and other possible IgG4-related lesions are listed in Table 2.…”

“…with type 1 AIP hypophysitis [107] skull and vertebral lesions [108][109][110] dacryoadenitis [103] neurosensory hearing loss [4] orbital lesions [109] sialoadenitis [103] chronic thyroiditis [4] meningitis [111] hilar lymphadenopathy [88] inflammatory pseudotumors esophagitis [112] interstitial pneumonitis [104] breast [113] sclerosing mesenteritis [114,115] sclerosing cholangitis [21,35,54] lung [116,117] Rosai-Dorfman disease [118,119] retroperitoneal fibrosis [105] liver [35,36,104,120] gastroenteritis [121] tubulointerstitial nephritis [106] gastric ulcer [4] vasculitis [122] swelling of the papilla of Vater [123] neuropathy [124] with type 2 AIP hepatopathy [35] myopathy [125] inflammatory bowel diseases [2,4,12,14] (ulcerative colitis and Crohn's disease)…”

IgG4-Related Disease and the Spectrum of Mimics in Rheumatology

“…Rarely tumor masses in the kidneys or damage to the glomeruli are observed. However, such locations of IgG4-RD may be found in the literature too [70]. Moreover, involvement of the kidneys may be divided into directly related to the location of infiltration in the parenchyma, and indirectly related to infiltration of structures of the urinary system in the course of retroperitoneal fibrosis.…”

“…Recently, also a case of renal amyloidosis AA in the course of IgG4-RD was reported. It is estimated that kidney involvement occurs in about 15% patients with IgG4-RD [70]. Besides symptoms of renal insufficiency in patients with IgG4-TIN, increased serum concentration of IgG and IgG4 is observed.…”

“…The infiltrate observed in IgG4-MGN composed of IgG4 cells in the wall of glomerular capillaries may imitate primary membranous nephritis. Detection of antibodies against phospholipase A2 receptor (anti-PLA2R), which do not occur in IgG4-MGN, may be then helpful [70].…”