IgG4-related kidney disease
Takako Saeki and Mitsuhiro Kawano
KI 0ct 2013
Sandeep G Huilgol
Outline of discussion
• BRIEF OVERVIEW OF IgG4-RD
• CLINICAL FEATURES OF IgG4-RKD
• LABORATORY FEATURES OF IgG4-RKD
• IMAGING FEATURES OF IgG4-RKD
• PATHOLOGICAL FEATURES OF IgG4-RKD
– Tubulointerstitial lesions
– Glomerular lesions
• DIAGNOSIS OF IgG4-RKD
• DIFFERENTIAL DIAGNOSIS
• TREATMENT AND CLINICAL COURSE OF IgG4-RKD
BRIEF OVERVIEW OF IgG4-RD
• First case described in 1961 – Autoimmune pancreatitis
(Sarles et al.)
• In 2001, Hamano et al demonstrated that the serum level of
IgG4 was significantly elevated in patients with sclerosing
pancreatitis (now called type 1 AIP).
• In 2003, (Kamisawa et al.) reported the presence of numerous
IgG4-positive plasma cell infiltrates in both the pancreatic and
extrapancreatic lesions of type 1 AIP and proposed a new
clinicopathological entity: IgG4-related systemic disease.
• IgG4-RD mainly affects middle-aged to elderly men,
many of whom have allergic conditions.
• Lesions seen in several organs
• Clinical symptoms vary depending on the affected
organ, they are relatively mild
• IgG4-RD is diagnosed from a combination of clinical,
serological, and radiological findings, along with
• The feature essential for a pathological diagnosis
- increased number of infiltrating IgG4-bearing
plasma cells within the involved organ(s).
• Other key histopathological features include a
– Dense lymphoplasmacytic infiltrate,
– Fibrosis arranged at least focally in a storiform
– Increased number of eosinophils may also be
• Several mechanisms - autoimmunity, allergy, or innate
immunity have been discussed,
• The role of IgG4 in IgG4-RD and the pathogenesis of
IgG4-RD is poorly understood.
• Predominance of a Th2-cell response and activation of
regulatory T cells at affected sites have been commonly
confirmed in various organs in association
• Production of IL-4, IL-10, and TGF-b is also markedly
increased in IgG4-TIN compared with other types of
CLINICAL FEATURES OF IgG4-RKD
• Male predominance (73–87%).
• Average patient age is about 65 years.
• Systemic symptoms are relatively mild.
• The condition usually becomes clinically apparent
when renal dysfunction and/or renal radiographic
abnormalities occur, during systemic examination for
extrarenal IgG4-RD or by chance.
• Patients with IgG4-RKD have IgG4-related
extrarenal lesions, the salivary glands, lacrimal
glands, lymph nodes, and pancreas being
• Edema may be evident in patients with IgG4-
RKD accompanied by glomerular lesions or in
patients with hydronephrosis due to
LABORATORY FEATURES OF IgG4-RKD
• Polyclonal hypergammaglobulinemia is a characteristic
feature of IgG4-RKD.
• 30% of patients with IgG4-RD have normal serum IgG4
• Almost all patients with IgG4-RKD have an elevated
serum IgG4 level, and 90% have an elevated serum
total IgG level.
• Hypocomplementemia and a high serum IgE level are
also characteristics, being evident in 50–70% and 70%
• ANA and RA are often positive.
• Anti-DNA, anti- SS-A, anti-SS-B, anti-Sm, and
anti-RNP antibodies are usually negative.
• The level of C-reactive protein is usually low,
and cryoglobulin, M-protein, and
antineutrophil cytoplasmic antibodies are not
• Although nearly half of all patients with IgG4-RKD
have proteinuria (and some have hematuria).
• Nephrotic range proteinuria is rarely detected,
except when glomerular lesions such as
membranous nephropathy are also present.
• Kidney function varies from normal to renal failure,
and the development of renal dysfunction also varies
from relatively acute to slowly progressive
IMAGING FEATURES OF IgG4-RKD
• Abnormalities of the kidney- this is a characteristic
feature that distinguishes the disease from other
types of TIN.
• Most common finding of enhanced computed
tomography is multiple low-density lesions (65%)
• Diffuse kidney enlargement (20–30%)
• Mass lesions(3–27%).
• Renal pelvic lesions - diffuse thickening of the
pelvic wall with a smooth intraluminal surface.
• Gallium scintigraphy and fluorodeoxyglucose
position emission tomography are helpful in
identifying not only renal but also extrarenal
PATHOLOGICAL FEATURES OF IgG4-RKD
• A dense lymphoplasmacytic infiltrate with an
increased number of IgG4-positive plasma
cells and fibrosis is a key feature of the
• Plasma cell rich TIN with an increased number
of IgG4-positive plasma cells and fibrosis.
• Storiform fibrosis - critical histopathological
feature of IgG4-RD.
• A unique characteristic feature of IgG4-TIN is nests of
inflammatory cells with irregular fibers surrounding them.
• This is usually revealed by periodic acid, methenamine silver
staining, and therefore it is not described in extrarenal organs.
• ‘bird’s-eye fibrosis’ to describe this feature, because it
resembles the ‘bird’s eye’ grain pattern of maple
• Eosinophil infiltration, extension of lesions into the renal
capsule, a well-defined regional lesion distribution, and a
TREATMENT AND CLINICAL COURSE OF IgG4-