Long-term renal survival of γ3-heavy chain deposition disease: a case report.

ABSTRACT

BACKGROUND: Monoclonal immunoglobulin deposition disease (MIDD) is characterized by the non-amyloid deposition of monoclonal immunoglobulin fragments in the basement membranes. Heavy chain deposition disease (HCDD) is a type of MIDD. HCDD is an extremely rare disease, and only three cases have been reported in Japan up to the present. The prognosis of HCDD is very poor, and optimal treatment has not been established. Only a few cases of HCDD with favorable long-term renal prognosis have been reported to date. CASE PRESENTATION The authors describe a 61-year-old woman who presented with massive proteinuria, progressive kidney impairment, and hypocomplementemia. Kidney biopsy was performed for a precise diagnosis. On light microscopy, glomerules were lobulated and presented with nodular sclerosing glomerulopathy with membranoproliferative glomerulonephritis-like features. Immunofluorescence studies were positive for IgG, C3, and C1q within the mesangial nodules and in a linear distribution along the capillary walls without associated deposition of light chains. Staining for IgG showed the presence of linear deposits along tubular basement membranes. The analysis of the IgG subclass stain demonstrated intense positivity for IgG3 only. Electron microscopy revealed non-organized electron-dense deposits in the expanded mesangial area and inner aspect of the glomerular basement membranes. In accordance with the histological findings, we diagnosed γ3-HCDD. There was no evidence of plasma cell dyscrasia as a result of bone marrow aspiration. Serum and urine monoclonal proteins were not detected by immunoelectrophoresis and immunofixation electrophoresis. The serum free light chain ratio was within normal range. At first, prednisolone was administrated at a dose of 40 mg/day. However, a therapeutic effect was not observed. Urinary protein was not decreased and renal function further deteriorated. Therefore, melphalan plus prednisolone (MP) therapy was initiated. After 4 courses of MP therapy, the clinical parameters, including proteinuria, serum creatinine, albumin, and complement level (C3 and C4) were ameliorated. To date, the patient has been followed for 28 months, and long-term renal survival has been observed. CONCLUSIONS: In this case, hematologic disease such as multiple myeloma was not detected; however, MP therapy was effective. Recently, the novel concept of monoclonal gammopathy of renal significance (MGRS) has been reported. MIDD, which includes HCDD, is one category of MGRS. In MGRS, aggressive chemotherapy may induce favorable renal outcomes.