DISCUSSİON
IgG4-RD is a fibroinflammatory disease involving almost all organs.
Patients may be asymptomatic or have severe symptoms. Clinical diagnosis
of the disease may be difficult or the findings may be confused with
other diseases. The American College of Rheumatology/European League
Against Rheumatism IgG4-RD determined classification criteria (4). The
disease progresses with tissue and organ involvement, IgG4 level is
usually high, it can also be found normal. IgG4-RD can lead to fibrosis
and can cause to organ failure Tissue biopsy is important to support the
diagnosis (1, 5). While the disease is first described as associated
with autoimmune pancreatitis, it can affect organs such as the thyroid,
salivary gland, biliary tract, and kidney etc (6, 7).
The kidney is involved in approximately 20% of patient with IgG4-RD.
The most common kidney disease is TIN. Retroperitoneal fibrosis can
cause to obstructive acute renal injury (ARI). Rarely, IgG4-RKD can
represent as a glomerular disease, especially as membranous nephropathy
(MN) (8).
IgG4-related TIN, has been identified as a part of systemic IgG4-RD. On
biopsy, TIN shows an IgG4 + plasma cell-rich infiltrate, and may show
tubulointerstitial immune complex deposits. Saeki et al evaluated 23
patients with renal parenchymal injury, and more than 60% of them had
TIN. Light microscopy demonstrated dense cell infiltration with fibrosis
and tubular atrophy. The infiltrate was predominantly composed of plasma
cells and lympho-cytes, and also eosinophils in some patients (8-10).
IgG4-RD with TIN cases presented with hypertension, elevated serum
creatinine and IgG4, proteinuria and eosinophilia have been reported
(11, 12).
CT is the primary imaging modality used to examine patients with
suspected IgG4-RD. Multiple low-density lesions on enhanced CT are the
most common radiologic finding in IgG4-related TIN, but diffuse
bilateral renal swelling may be observed when severe renal failure is a
contraindication for the administration of contrast medium. Kidney
abnormalities on CT imaging have been observed in nearly 70 % of
patients with IgG4- RD (13-16).
In a study, 9 patients described with IgG4-RD MN. All patients showed
MGN on biopsy, presented with proteinuria (mean 8.3 g/day), and most had
elevated serum creatinine (mean 2.2 mg/dl). All biopsies showed a
pattern of MGN with subepithelial deposits in a membranous pattern seen
by immunofluorescence (IF), electron microscopy, or light microscopy,
including immunoperoxidase staining for IgG4. In another study about
IgG4-RD MN, interstitial IgG4+ plasma cell infiltration (>
10/hpf ), and IgG4-positive plasma cells account for more than 40% of
IgG+ plasma cells detected in immunohistochemistry staining (14, 15,
17).
The efficacy of glucocorticoids and rituximab (RTX) in the treatment of
IgG4-RD has been demonstrated. IgG4-related disease usually responds to
high-dose glucocorticoids, with an average dose of 40mg/day, which is
subsequently tapered. In a study, partial and complete response observed
in all patients after glucocorticoid and RTX treatment. International
consensus recommends a much more gradual tapering of the dose, over a
period of 3–6 months. With this dosing scheme, the rate of relapses was
23% (2, 18, 19). Good response to RTX has been obtained in IgG4-related
disease. In another study, RTX was used as induction therapy at a dose
of 1000 mg on days 1 and 15, without simultaneous corticosteroids (26
patients) or with a gradual reduction of the dose of the latter during
the first 2 months (4 patients). Using a responder index to measure
IgG4-RD activity, 97% of the individuals had an activity response at 6
months, with 47% incomplete remission, and 40% maintaining that
response at 12 month (20). In a French study, patients who received
rituximab treatment 375 mg/m2 once a week (4 doses)
and 1000 mg on the 1st and 15th days were evaluated, the response to the
treatment was 93.5%. The relapse rate was 41.9% (after mean 19.0 ±11.5
months) and relapse after retreatment was 27.2% (21).
In our study, we evaluated a 52-year-old patient who presented with
proteinuria and acute kidney injury. The diagnosis of IgG4-RD were made
according to American College of Rheumatology/European League Against
Rheumatism classification criteria for IgG4-related disease in our case
(4) [Hypocomplementemia (6 points), IgG4 levels (4 points), IgG4
staining level in biopsy (14 points) and radiological kidney involvement
(10 points), total 34 points] (Table 1). The patient’s clinical course
was stable and proteinuria regressed after steroid treatment. The
complete urinalysis, protein, erythrocyte and leukocyte were negative.
In his control after 60 days, serum urea decreased to 53.1 mg/dL and
creatinine to 1.71 mg/dL. Glucocorticoid dose reduced to 15 mg/day.
In conclusion, renal involvement in IgG4-related disease is rare. Early
diagnosis and treatment and management of the disease are important for
survival and progression of the disease.