ReviewIgG4-related kidney disease – A review
Introduction
IgG4-related disease (IgG4-RD) is a recently recognized systemic autoimmune disorder characterized by high levels of serum IgG4 and dense infiltration of IgG4-positive cells in multiple organs [1], [2]. The diagnosis of IgG4-related disease depends on the characteristic morphologic appearance, which includes a dense lymphoplasmacytic infiltrate, storiform fibrosis, obliterative phlebitis, and increased numbers of IgG4+ plasma cells. Deshpande et al. [3] nevertheless stresses careful clinicopathologic correlation, which cannot be superseded by the morphologic criteria alone.
This systemic disease was first recognized as a disease of the pancreas [sclerosing lymphoplasmacytic pancreatitis also referred as autoimmune pancreatitis (AIP)] by Sarles et al. in 1961 [4]. IgG4-RD disease has now been described in nearly every organ system, including the kidney, liver (sclerosing cholangitis, pseudotumor), gallbladder (IgG4-related cholecystitis), salivary and lacrimal glands (chronic sclerosing sialadenitis/Kuttner's tumor; dacryoadenitis; Mikulicz disease), lung and pleura (interstitial pneumonitis, inflammatory pseudotumor, fibrinous pleuritis), orbit (pseudotumor), breast (sclerosing mastitis, inflammatory pseudotumor), retroperitoneum (retroperitoneal fibrosis), cardiovascular system (periaortitis; inflammatory aortic aneurysm; pericarditis), lymph nodes (lymphadenopathy with various histologic patterns), skin (cutaneous pseudolymphoma), pituitary gland (infundibulo-hypophysitis), thyroid (Riedel thyroiditis; Hashimoto thyroiditis), and prostate (prostatitis) [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16]. The fibroinflammatory lesions show remarkable histologic similarity in these different organs [3], [17].
Renal involvement in IgG4-RD in any form is collectively referred to as IgG4-related kidney disease (IgG4-RKD) [18], [19], [20]. The most common renal involvement by IgG4-RD is in the form of plasma cell rich tubulointerstitial nephritis (IgG4-TIN). Other renal manifestations and associations of IgG4-RD include membranous glomerulonephritis (MGN) with or without IgG4-TIN, IgA nephropathy, membranoproliferative glomerulonephritis, mesangioproliferative immune complex glomerulonephritis, sclerosing pyelitis, IgG4-related plasma cell arteritis and hydronephrosis associated with IgG4 related retroperitoneal fibrosis or ureteral inflammatory pseudotumor [1], [18], [19], [20], [21]. To date, sporadic case reports and occasional series of IgG4-RD have been described in the literature. In this review, we discuss the recent literature related to IgG4-RD as it affects the kidney.
Section snippets
Clinical and radiologic features
IgG4-RKD like other IgG4-RD is found mostly in older men. It presents commonly as acute or progressive chronic renal failure, radiographic mass lesion, or both [22]. The mean serum creatinine in the Raissian et al. [22] biopsy series, was lower in patients with renal tissue specimens obtained primarily for mass lesions compared to those biopsied for renal failure (1.4 mg/dl versus 4.2 mg/dl, respectively). Patients with IgG4-TIN alone may have mild proteinuria and microscopic hematuria; those
Laboratory features
Almost 80% of patients with IgG4-RKD, have hypergammaglobulinemia or elevated serum total IgG and/or IgG4 levels [1], [24]. The finding of an elevated serum IgG4 alone is not specific for IgG4-RD, as 5% of the normal population and 10% of pancreatic cancer patients have an elevated serum IgG4 level [25]. Other common laboratory features are hypocomplementemia (decreased serum C3 and/or C4 levels), a high serum IgE level, and peripheral blood eosinophilia (33–48%) [1], [22]. Some patients have a
Macroscopic features
IgG4-RKD is mostly diagnosed on renal biopsies and so gross findings have not been studied extensively.
Microscopic features
IgG4-RKD can be described histologically as changes to the different compartments in the kidney, including the tubules and interstitium, the glomeruli, and the vessels.
Diagnosis
The diagnostic criteria proposed in two large series give an overview of IgG4-RKD. Raissin et al. [22] in a large series has proposed the diagnostic criteria of IgG4-related TIN. The histologic criteria of plasma cell-rich TIN with more than 10 IgG4+ plasma cells/high power field (hpf) in the most concentrated field is kept as a mandatory criteria, while TBM immune complex deposits by immunofluorescence, immunohistochemistry, and/or electron microscopy present in more than 80% of biopsy
Differential diagnosis
IgG4-RKD is not a distinct histopathologic entity and should be suspected in all biopsies with significant interstitial inflammation rich in plasma cells and in which clinical, radiologic, and laboratory features point toward this disorder. These lesions may be seen in pauci-immune glomerulonephritis, autoimmune TIN, lupus nephritis, chronic pyelonephritis, idiopathic hypocomplementemic TIN, TIN associated with Sjogren's syndrome, and granulomatosis with polyangiitis. As mentioned earlier, most
Treatment and prognosis
IgG4-TIN shows a favorable response to steroid therapy in most cases, like other IgG4-RD. The Saeki et al. [1] series showed rapid improvement in creatinine levels following treatment with steroids in 18 out of 19 (>90%) patients within 4 weeks. Similar result has been shown in the Raissian et al. [22] series, wherein 17 of 19 (∼90%) patients showed rapid response. Although TIN of any cause may respond to steroid therapy, IgG4-TIN tends to show a more brisk response, even in cases with severe
Conclusion
In conclusion, IgG4-RKD is the renal manifestation of a systemic autoimmune disease, usually in the form of plasma cell-rich TIN with immune complex deposits. MGN may also be seen in IgG4-RD, with or without concurrent TIN. IgG4-related plasma cell arteritis has recently been described in the kidney. The fibroinflammatory manifestations in IgG4-RKD (including TIN) generally show a brisk response to steroid therapy; refractory patients may respond to rituximab. Long term follow-up data of these
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Autoimmune diseases in the kidney
2019, The Autoimmune DiseasesRole of complement system in patients with biopsy-proven immunoglobulin G4–related kidney disease
2018, Human PathologyCitation Excerpt :Our kidney biopsy showed that most of our patients presented as IgG4-TIN, which is in agreement with previous investigations [19,20]. However, IgG4-RKD can manifest glomerular lesions, including MN, IgAN, and membranoproliferative glomerulonephritis [21]. IgG4-MN has been reported in about 10% of cases of IgG4-RKD [22].
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2016, Revue Francophone des LaboratoiresAn overview of the diagnosis and management of immunoglobulin G4-related disease
2016, CMAJCitation Excerpt :Stone and colleagues reported that polyclonal hypergammaglobulinemia was detected in the sera of 80% of patients and an elevated level of IgE in 60% of patients.47 One-third of patients have hypocomplementemia; this finding may be particularly associated with IgG4-related kidney disease,13 presumably as a consequence of proteinuria. A systematic review that examined the clinical features of patients with a diagnosis of IgG4-related disease showed that only 32% and 20% of patients had detectable antinuclear antibodies and rheumatoid factor, respectively.47,50
Differential diagnosis of IgG4-related pancreatitis and pancreatic cancer by MRI features and its correlation with serum IgG4 level
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