A Case of MGRS-Associated C3 Glomerulonephritis following Acute COVID-19 Infection

Introduction: C3 glomerulonephritis (C3GN) is a proliferative GN resulting from mutations or functional inhibition of regulatory proteins in the alternative complement pathway. Rarely, inhibition of complement-regulating proteins may result from monoclonal gammopathy. We present a case of C3GN associated with monoclonal gammopathy of renal significance (MGRS) following acute COVID-19 infection. Case Description: A 60-year-old female with a history of hypertension developed new edema one month following acute COVID-19 infection which had been managed conservatively as an outpatient. She was subsequently admitted for nephritic syndrome with worsening hypertension, serum creatinine of 1.9 mg/dl, and proteinuria of 2.4g/24hr. Urinalysis was positive for protein and blood with dysmorphic RBCs on urine sediment. Serologic evaluation was notable for a new IgG Lambda M-protein on SPEP with a normal free-light chain ratio and low C3 level. Blood cultures, C4, ANA, cryoglobulins, ANCA, HIV, HBV, HCV, and were normal/negative. Despite adequate blood pressure control with nifedipine and irbesartan, proteinuria and hematuria persisted for >8 weeks. Kidney biopsy showed neutrophilic glomerulitis with a membranoproliferative pattern. Immunofluorescence showed only mesangial and capillary C3 deposits. Pronase digestion of paraffin samples did not reveal masked immunoglobulin deposits. Functional complement testing demonstrated increased C3 convertase activity and negative for autoantibodies to complement regulatory proteins. Subsequent bone marrow biopsy revealed a 5% IgG Lambda plasma cell clone, consistent with MGRS-associated C3GN. She was treated with six cycles of cyclophosphamide, bortezomib, and dexamethasone resulting in improvement in proteinuria and serum creatinine. Discussion: C3GN is a rare variant of MGRS not associated with infection. Although causality between the preceding COVID-19 infection and the subsequent C3GN cannot be proven, other cases of post-viral MGRS, have been reported. Nephrologists should be aware that not all kidney disease occurring after COVID-19 is due to tubular injury or collapsing glomerulopathy.