Focal Segmental Glomerulosclerosis Associated With Invasive Thymoma

Nephrotic syndrome in a patient with thymic diseases has been reported as thymoma-associated nephropathy. Most of these patients have minimal change nephropathy, which usually occurs after treatment of the thymoma (1). Here, we report a patient with focal segmental glomerulosclerosis (FSGS) whose symptoms improved after surgical treatment of invasive thymoma. In September 2006, a 72-year-old Japanese woman was admitted to another hospital for severe edema of her lower extremities, nausea, and loss of appetite. Nephrotic syndrome was diagnosed, with urinary protein excretion of 7.4 g daily, serum creatinine of 1.4 mg/dL, serum albumin of 1.4 mg/dL, and total cholesterol of 346 mg/dL. Prednisolone was administered at 40 mg/day combined with methylprednisolone pulse therapy (1000 mg/day for three days); however, her renal failure progressed rapidly and the serum creatinine rose to 6.8 mg/dL five days after the start of steroid therapy. Hemodialysis was started because of anuria and congestive heart failure. Maintenance hemodialysis was continued three times weekly for 4 h per session. The pathogenesis of her acute renal dysfunction remained unclear because a renal biopsy was not performed. Her steroid therapy was slowly tapered and was discontinued in January 2007. Two months later, she developed an intermittent high fever that was resistant to antibiotics and of unclear origin. Accordingly, she was admitted to our hospital for further evaluation. On admission, the patient’s temperature was 37.7°C, leukocyte count was 6800/mL, and C-reactive protein was 0.6 mg/dL. A chest CT scan showed a large anterior mediastinal mass measuring 65 ¥ 30 ¥ 110 mm that was strongly enhanced by intravenous contrast medium (Fig. 1A). Although antiacetylcholine receptor antibody was positive at 4.5 nmol/L (normal range: 0.2), the Tensilon test was negative. Subclinical myasthenia gravis was diagnosed. On 17 August 2007, the patient’s anterior mediastinal mass was removed surgically by video-assisted thoracoscopy. Histological examination showed an invasive thymoma of type B2, according to the WHO classification, and Masaoka clinical stage 3. She underwent adjuvant radiation therapy to a total dose of 46 Gy postoperatively. On 9 September 2007, a renal biopsy was performed. Light microscopic examination of 24 glomeruli revealed global sclerosis of four glomeruli (Fig. 1B). One glomerulus showed segmental sclerosis and adhesion to Bowman’s capsule (Fig. 1C). Immunofluorescence was negative for IgG, IgA, IgM, and complement factors C3 and C1q. Electron microscopy showed widespread fusion of epithelial cell foot processes and wrinkling of the glomerular basement membrane, but there were no electron-dense deposits (Fig. 1D). These findings were consistent with a diagnosis of FSGS. Her urine output was approximately 300 mL/day before surgery, but it increased gradually up to 1200 mL/day by two weeks after the operation. Hemodialysis was discontinued on 22 October 2007.As of July 2010, she is doing well, and her serum creatinine is 1.1 mg/dL, serum albumin is 4.0 g/dL, and urinary protein excretion is 0.10 g/day. In most previous reports, the occurrence of a thymoma occurred first and nephrotic syndrome followed 1–15 years after a successful thymectomy or medical treatment (1). Cases where nephrotic syndrome precedes the discovery of thymoma are quite rare. Histologically, minimal change nephropathy is the most common pathology, along with some reports of FSGS (2) and membranous nephropathy. As the cause of nephrotic syndrome that arises several years after thymectomy, the following hypothesis has been proposed. Thymectomy induces T-cell dysfunction, leading to nephrotic syndrome via increased production of cytokines, which increases glomerular basement membrane permeability. However, it takes several years until alterations of lymphocyte function become manifest (3). On the other hand, patients with thymoma have been well documented to have impaired cellular and humoral immunity originally. The thymus is the primary lymphoid organ where T-lymphocytes undergo maturation; therefore, immune dysfunction could be caused by thymoma, as well as by thymectomy (4). In our patient, nephrotic syndrome and acute renal failure were the presenting features of the thymoma. Steroid therapy was not effective and maintenance hemodialysis was needed. Following thymectomy, renal function improved and hemodialysis could be discontinued. This case indicates that invasive thymoma itself may contribute to the pathogenesis of FSGS, though this histological finding was gained after kidney function had been resolved. Letters to the Editor 210