Monoclonal and monotypic immunoglobulin-related kidney diseases in young people: literature review including evolving entities.

Monoclonal gammopathy, paraprotein secreted by a clonal B-lymphoproliferative or plasma cell disorder, is quite rare in children and adolescents and may be transient. Kidney injury related to monoclonal proteins, or monoclonal gammopathy of renal significance (MGRS), is correspondingly rare and may be relatively unfamiliar to pediatric nephrologists when encountering such diagnoses on kidney biopsy (e.g., amyloid, light chain tubulopathy, light chain cast nephropathy). Several recently described glomerulonephritides with monotypic deposits, characterized by deposits of a single heavy chain and a light chain, without a matching clone in serum or bone marrow, are emerging as more common in this age group than true MGRS, such as proliferative glomerulonephritis with monoclonal immunoglobulin deposit (PGNMID), IgA nephropathy with light chain restriction, monotypic membranous nephropathy, and membranous-like nephropathy with masked IgG-kappa (MGMID). PGNMID may arise after infection or other triggers and, in children, is often associated with hypocomplementemia. A recent adult study employing sensitive bone marrow immunoglobulin repertoire sequencing has failed to identify a true clone in many cases, particularly those with IgG3 glomerular deposits. Unfortunately, PGNMID has a propensity for post-transplant recurrence. The pathophysiology, etiology, and treatment for PGNMID and other monotypic entities remain yet to be elucidated in children and adults. Nevertheless, a screening immunofluorescence microscopy panel that includes kappa and lambda light chains is essential for biopsy diagnosis, with confirmation sometimes requiring additional studies such as IgG subclasses and/or antigen retrieval immunofluorescence. This review aims to comprehensively cover monoclonal and monotypic immunoglobulin-related kidney disease in young people.