A 59-year-old Japanese woman with treatment history of hypertension for 1 year suddenly developed peripheral edema. Primary care doctor detected hematuria and proteinuria, and she was referred to our hospital.
The initial laboratory results are summarized in Table 1. Massive proteinuria and hypoproteinemia were noted. Serum and urine protein electrophoresis revealed a monoclonal IgG-lambda peak, but bone marrow aspiration showed <10% plasma cells, which did not meet the diagnostic criteria of multiple myeloma. Although C3 hypocomplementemia was present, titers for antinuclear antibody, anti-double-stranded DNA antibody, ASO, and anti-PVB19 IgM antibody were within the normal range.
The first renal biopsy showed MPGN pattern with endocapillary proliferation (Figure 2A). Only one glomerulus was obsolescent in LM sections containing 20 glomeruli. Congo red staining was negative. IF staining for IgG was positive mainly along the glomerular capillary walls, whereas that for IgA and IgM was both negative (Figure 2B). IF IgG subclass staining demonstrated sole deposition of IgG3 (Figure 2C). Strong lambda-light chain deposition on IF staining (Figure 2D) and corresponding EDD mainly in the mesangial and subendothelial areas were observed (Figure 2E). There were also small amounts of subepithelial EDD (Figure 2E). On the other hand, IF kappa-light chain staining was rather weak and seemed non-specific (data not shown). Positive staining for NAPlr and plasmin activity was observed in the glomeruli with a similar distribution, but the staining pattern of them was different from that of complement C3 (Figure 2F). Neither fibrils nor powdery deposits were observed under EM, and no EDD were found on TBM.
Although infection-related PGNMID was suspected, detailed examination could not detect the focus of infection. Therefore, we started steroid treatment, and partial remission of nephrotic syndrome (proteinuria level of about 0.5 g/g Cr) was observed in association with normalization of serum C3 levels. The dose of steroids was gradually tapered and retained at 5 mg daily, which maintained her remission for 2 years. However, severe nephrotic syndrome relapsed (proteinuria level, 5-10 g/day) in association with decrease in the C3 level (63.7 mg/dL). The second renal biopsy was performed about 3 years after the first and showed similar pathological findings to those of the first (Figure 3A), but 5 out of 26 glomeruli were globally sclerotic in LM sections, suggesting the progression of histological chronic lesions. NAPlr and plasmin activity were completely negative at this time (Figure 3B). Although the dose of steroids was increased, the patient was complicated by severe hypogammaglobulinemia (IgG level, 100-300 mg/dL), which made it difficult for us to further intensify immunosuppressive therapy. The development of overt multiple myeloma was ruled out by the feature of repeat bone marrow aspiration that was performed about 4 years after the first. Her condition progressed to end-stage renal disease (ESRD), and she became dialysis-dependent 5 years after disease onset.