IgG Heavy-Chain Deposition Disease: An Overlooked Cause of ESRD

Introduction: Heavy Chain Deposition Disease (HCDD) is a rare type of Monoclonal Immunoglobulin Deposition Disease (MIDD) in which structurally altered monoclonal immunoglobulin heavy chains are deposited in multiple organs, including kidneys - without light chain deposition. Classified under Monoclonal Gammopathy of Renal Significance, HCDD presents as nephrotic-range proteinuria, hypertension & rapid progression to ESRD. Case Description: A 55 y/o man with T-cell lymphoma s/p allogeneic stem cell transplant, with worsening anasarca, renal dysfunction & sob. Labs: Cr 6.95 mg/dL, UPCR 7.7, Albumin 2.7 g/dL Immunofixation: Faint free lambda chains. SPEP lacked a definitive M-spike Renal biopsy: Nodular glomerulosclerosis with linear deposition of IgG heavy chains on immunofluorescence Bone marrow biopsy: 5–10% lambda-restricted plasma cells FISH: IGH rearrangement & gain of chromosome 1q Urgent dialysis, chemotherapy, & dexamethasone were initiated to target the plasma cell clone, but he remained dialysis-dependent, reflecting the fulminant course of HCDD. Discussion: HCDD can progress to ESRD within 3 months, requiring kidney biopsy due to low paraprotein burden. Chromosomal abnormalities 1q gain/IGH rearrangement predict poor outcomes despite minimal clonal burden, supporting an underlying monoclonal disorder. Patients are at increased risk for amyloidosis & multiple myeloma, necessitating lifelong follow-up.FISH panelFlow cytometry