JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
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Characteristics of proliferative glomerulo-nephritis with monoclonal IgG deposits associated with membranoproliferative features.

BACKGROUND: Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) associated with membranoproliferative features is an extremely rare entity. Information on clinicopathological features and prognosis in this entity is limited.

METHODS: We reviewed 5,443 renal biopsies processed at our department, and identified 4 patients with PGNMID associated with membranoproliferative features. We evaluated clinicopathological features and outcomes in these patients, and characterized paraprotein deposits by immunofluorescence studies.

RESULTS: Three out of 4 patients had nephrotic syndrome with renal insufficiency at presentation. Cryoglobulin or monoclonal protein in serum and urine was not detected. Renal biopsy showed membranoproliferative features with or without nodular formation. Tubulointerstitial and vascular alterations were mild in three patients. All patients had glomerular IgG-kappa deposits. Heavy chain subclass analysis performed in 3 patients showed IgG3 deposits. Immunofluorescence studies using antibodies specific for gamma-heavy chain C(H)1, C(H)2, and C(H)3 domains and gamma3 hinge did not show any apparent deletion. Confocal microscopy revealed glomerular colocalization of light and heavy chains. On electron microscopy, granular deposits were predominantly mesangial and subendothelial. All patients were treated with steroids and cytotoxic agents, but no effect on proteinuria was observed. The renal outcome was progressive in all patients. Early death was observed in two elder patients. No patient had overt myeloma or lymphoma at presentation or over the course of follow-up (mean 43 months).

CONCLUSIONS: Our study suggests a predominance of IgG3-kappa glomerular deposits of nondeleted whole immunoglobulin molecules in PGNMID associated with membranoproliferative features. The clinical outcome in patients with this entity appears to be poor.

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