Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits: An Immunologic Crossroads

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is largely regarded as a form of monoclonal gammopathy of renal significance; however, 70-80% of cases lack evidence of an associated monoclonal lymphoproliferative disorder. Emerging evidence suggests it is a shared clinicopathologic manifestation of multiple, distinct disease etiologies including infection, autoimmunity, complement dysregulation, and neoplasia. Development of a more precise, etiology-based system of classification is hindered by limitations in adequately characterizing the clonal nature of monotypic deposits in renal tissue. Furthermore, the current body of evidence evaluating effective treatment options for PGNMID is limited by retrospective data, small sample sizes, and variability in treatment regimens. As a result, treatment strategies are largely extrapolated from established therapies used in overt hematologic malignancies.

In this review, we discuss the classification, pathogenesis, clinicopathologic features, diagnostic challenges, and treatment approach for PGNMID.

The heterogenous nature and lack of consensus to guide the management of PGNMID highlights the need for an individualized and multidisciplinary team approach involving nephrologists, hematologists, and nephropathologists. Practicing clinicians need to be aware of the limitations of diagnostic tools used in routine clinical practice.