Endocarditis-Associated C3-Dominant Glomerulonephritis in a Patient With a Solitary Kidney

Infective endocarditis (IE) is still seen globally with acute kidney injuries remaining a common complication of the disease. Histological specimens often display either diffuse or focal endocapillary proliferation as well as neutrophilic infiltration in endocarditis-related renal disease. C3-dominant glomerulonephritis (C3GN) utilizes mechanisms of complement activation unique from IE-associated glomerulonephritis. In C3GN, micrographic review may reveal scattered accumulation of C3 fragments with subepithelial hump formation and mesangial electron-dense deposits that help solidify the diagnosis of this recently discovered pathological phenomenon. Herein, we summarize a clinical case of likely IE-related C3GN without hypocomplementemia in a patient with a single kidney to help compare and contrast the key elements of each process. A 27-year-old Hispanic man with a past medical history of nephrectomy for renal donation presented to a community hospital with a high fever and altered sensorium. A serum creatinine of 6.98 mg/dL with unknown baselines, nephrotic-range proteinuria, and severe rhabdomyolysis plus methicillin-sensitive Staphylococcus aureus bacteremia were quickly discovered after admission. A later transesophageal echocardiogram showed a hypermobile vegetation along the anterior mitral valve leaflet confirming suspected IE. The patient’s serum C3 and C4 complement levels and antinuclear, myeloperoxidase, and proteinase-3 antibody titers were all within normal limits. A renal biopsy pursued in the etiological investigation of this non-oliguric acute kidney injury revealed a single subepithelial electron-dense deposit and granular immunofluorescent C3 staining in peripheral mesangial segments. Dominant C3 deposition without associated immunoglobulins can result from in situ localization of bacterial antigens promoting plasmin activation to recruit neutrophils and monocytes to initiate leukocyte-mediated damage. Immunosuppressive therapies for C3GN triggering antibody-independent activation of the alternative or lectin complement pathways may be merited where disease remission becomes difficulty to achieve.