Membranous Nephropathy With Monoclonal IgM Lambda Deposits in a Patient With IgM Monoclonal Gammopathy: A Case Report

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.

Light and heavy chain deposition revealed by repeat renal biopsy after inconclusive initial biopsy

Monoclonal gammopathy is a premalignant condition associated with an abnormal circulating immunoglobulin indicative of an expanded B cell clone. Apart from monitoring, no other intensive management is prescribed in these cases. Periodic bone marrow biopsies when free light chain imbalances are detected are used to spot incidental cases of multiple myeloma. New reports have suggested the existence of a monoclonal gammopathy of renal significance where a circulating antibody and normal bone marrow biopsy results may be associated with proteinuric renal disease due to monoclonal immunoglobulin deposition. We report a case of a 65-year-old male with an immunoglobulin G kappa monoclonal gammopathy of undetermined significance, chronic kidney disease, proteinuria, and an initial inconclusive renal biopsy. His chronic kidney disease worsened with persistence of 0.5 g of proteinuria. Given the finding of ongoing Bence Jones proteinuria, a repeat renal biopsy was done revealing monoclonal immunoglobulin G kappa deposition disease. Bone marrow biopsy showed 20% plasma cells that could be consistent with smoldering myeloma. The patient’s renal disease has stabilized after starting treatment for the monoclonal gammopathy of renal significance. This case illustrates the importance of renal biopsy in making the diagnosis of monoclonal immune deposition disease and monoclonal gammopathy of renal significance.

Development of lupus nephritis in a patient with previous scleroderma renal crisis

We present a case of scleroderma overlap syndrome with systemic lupus erythematosus (SLE) including complications of both scleroderma renal crisis and lupus nephritis. Our patient was initially diagnosed with undifferentiated connective tissue disease in 1996. A diagnosis of scleroderma was made in 2010 after she developed scleroderma renal crisis. She remained stable until 2016, when she presented with Salmonella bacteremia, renal failure, nephrotic range proteinuria and microscopic hematuria. Laboratory findings were consistent lupus with positive ds-DNA, hypocomplementemia and repeat renal biopsy showed lupus nephritis.

Relationship of Intrarenal Gene Expression and the Histological Class of Lupus Nephritis — A Study on Repeat Renal Biopsy

Objective.To study the role of tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK)/Fn14 and the interferon-inducible protein (IP-10)/CXCR3 axis in lupus nephritis (LN).Methods.We studied 113 patients with LN who had had repeat renal biopsies. Glomerular and tubulointerstitial messenger RNA expression of TWEAK, Fn14, IP-10, and CXCR3 were quantified.Results.Glomerular Fn14 expression decreased when changed from proliferative or mixed nephritis to membranous nephropathy (p = 0.016), and increased when changed from membranous to proliferative or mixed nephritis (p = 0.0006). On the other hand, tubulointerstitial TWEAK expression decreased when changed from proliferative or mixed nephritis to membranous nephropathy (p = 0.004), and increased when changed from membranous nephropathy to proliferative nephritis (p = 0.010). Tubulointerstitial IP-10 expression decreased when changed from proliferative or mixed nephritis to membranous nephropathy (p < 0.0001). Histological activity index correlated significantly with the glomerular expression of Fn14 (r = 0.421, p < 0.0001) and tubulointerstitial expression of TWEAK (r = 0.413, p < 0.0001) and IP-10 (r = 0.472, p < 0.0001).Conclusion.Glomerular Fn14 and tubulointerstitial TWEAK and IP-10 expression appeared to have consistent changes in relation to the histological class of LN and correlated with the histological activity index. Our findings suggest a specific role of these genes in the pathogenesis of LN.