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.