Challenges in the Diagnosis and Management of Immune Complex-Mediated Membranoproliferative Glomerulonephritis and Complement 3 Glomerulopathy

Immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) and complement 3 glomerulopathy (C3G) are rare, complement-mediated kidney diseases, previously classified under the group of kidney disorders termed membranoproliferative glomerulonephritis (MPGN) type 1, type 2, and type 3. Despite new advances in our understanding of IC-MPGN and C3G, several unmet needs persist in the diagnosis and management of patients with these nephropathies, due in part to their rarity and their overlapping clinical presentations, histologic features, and underlying pathophysiologies. This review summarizes our current understanding of the role of complement in IC-MPGN and C3G, and underlines the key histopathologic differences between the diseases. Using seven illustrative patient cases, we discuss consensus guideline treatment recommendations and the uncertainties, challenges, and considerations regarding the diagnosis and management of patients with IC-MPGN and C3G in clinical practice. The presented cases emphasize the need for a multidisciplinary approach encompassing primary care providers (PCPs), nephrologists, nephropathologists, and laboratory scientists. Key knowledge gaps are evaluated, including differential diagnoses, underlying pathologic mechanisms, and the lack of effective treatments targeting drivers of disease. As the therapeutic landscape evolves, an improved understanding of IC-MPGN and C3G is crucial to identifying optimal targeted-treatment strategies and facilitating a personalized approach to the management of these complex glomerular diseases.