C3 glomerulonephritis with light chain crystalline podocytopathy and non-crystalline proximal tubulopathy: a case report and integrative clinicopathologic analysis

This report describes a novel renal triad consisting of C3 glomerulonephritis (C3GN), light chain crystalline podocytopathy (LCCP), and non-crystalline light chain proximal tubulopathy (NC-LCPT) in a 41-year-old male presenting with nephrotic syndrome and rapidly progressive renal failure. Investigations revealed monoclonal IgG kappa paraproteinemia and isolated C3 hypocomplementemia. Renal histopathology demonstrated three distinct lesions: (1) C3GN with mesangial and capillary wall C3 deposits; (2) LCCP, featuring intralysosomal κ-restricted crystalline deposits in podocytes; and (3) NC-LCPT, manifesting tubular epithelial injury without crystal formation. This unique combination suggests concurrent and synergistic renal injury resulting from dysregulation of the alternative complement pathway and monoclonal immunoglobulin toxicity, consistent with the spectrum of monoclonal gammopathy of renal significance (MGRS). Although chemotherapy with bortezomib, cyclophosphamide, and prednisone was initiated, treatment was interrupted due to infection. Consequently, the patient progressed to end-stage renal disease within eight months. This case illustrates the aggressive nephrotoxic potential when complement-mediated glomerulopathy coexists with dual monoclonal immunoglobulin-induced glomerular and tubular damage. It emphasizes the critical need for early and integrated therapeutic strategies targeting both the clonal plasma cell population and complement activation to prevent irreversible renal failure. Comprehensive morphological and immunofluorescence analyses are essential for the accurate diagnosis of such complex overlapping nephropathies.