ABSTRACT
We report a case of membranous nephropathy with monoclonal immunoglobulin (Ig)M lambda deposits in a patient with IgM monoclonal gammopathy, in whom histological changes were observed on repeat renal biopsy. A 72-year-old Japanese woman was referred to our hospital because of massive proteinuria. A prominent increase in monoclonal IgM lambda level was identified, and she was diagnosed as having IgM monoclonal gammopathy of undetermined significance. Renal biopsy showed glomerular subepithelial electron-dense deposits that were found to be granular deposits of IgM lambda but not kappa or IgG by immunofluorescence staining, resulting in a diagnosis of membranous nephropathy with monoclonal IgM deposits. The second biopsy, which was performed 2 years later because of exacerbation of her nephrotic syndrome, demonstrated less immunofluorescence staining of IgM, and dominant IgG2 deposition without light chain restriction. Interestingly, immunostaining for thrombospondin-type-1-domain-containing-7A was positive in both renal biopsy tissues, although the second biopsy showed clearly stronger immunoreactivity. The effect of steroid therapy was limited; however, rituximab treatment improved both the hematological and renal abnormalities. Solitary deposition of IgM in membranous nephropathy is a quite rare condition. To our knowledge, this is the first case of monoclonal gammopathy of renal significance presenting as membranous nephropathy with monoclonal IgM deposits, in which chronological immunohistochemical changes were observed and rituximab therapy was effective.
ABSTRACT
BACKGROUND: Anti-glomerular basement membrane (GBM) glomerulonephritis does not usually coexist with another glomerulonephritis such as IgA nephropathy. We present a rare case having a combination of these two diseases, and furthermore, histological evaluation could be performed before and after the development of anti-GBM glomerulonephritis over a period of only10 months. CASE PRESENTATION: A 66-year-old woman was admitted with complaints of microscopic hematuria and mild proteinuria for the past 3 years. Serum creatinine level was normal at that time. The first renal biopsy was performed. Light microscopy revealed mesangial proliferative glomerulonephritis with fibro-cellular crescents in one out of 18 glomeruli, excluding one global sclerotic glomerulus. Immunofluorescence (IF) showed IgA and C3 deposition in the mesangium. Therefore, the diagnosis was IgA nephropathy. Eight months later, the patient's serum creatinine suddenly rose to 4.53 mg/dL and urinalysis showed 100 red blood cells per high power field with nephrotic range proteinuria (12.3 g/gCr). The serological tests revealed the presence of anti-GBM antibody at the titer of 116 IU/mL. Treatments were begun after admission, consisting of hemodialysis, plasma exchange, and intravenous methylprednisolone pulse therapy. At 4 weeks after admission, the second renal biopsy was performed. Light microscopy revealed crescents in 18 of 25 glomeruli, excluding six global sclerotic glomeruli. IF showed linear IgG deposition along the GBM in addition to granular IgA and C3 deposition. Based on these findings, the diagnosis of anti-GBM glomerulonephritis and IgA nephropathy was confirmed. Renal function was not restored despite treatment, but alveolar hemorrhage was prevented. CONCLUSIONS: We report a patient with a diagnosis of anti-GBM disease during the course of IgA nephropathy. This case strongly suggests that the presence of autoantibodies should be checked to rule out overlapping autoimmune conditions even in patient who have previously been diagnosed with chronic glomerulonephritis, such as IgA nephropathy, who present an unusually rapid clinical course.
