C3 Glomerulonephritis Diagnosed During Mid-Pregnancy

Introduction: C3GN is a rare glomerular disease characterized by dysregulation of the alternative complement pathway. It is a progressive kidney disease with a significant risk of progression to ESRD. Management focuses on supportive care, immunosuppressive therapy in select cases, and emerging treatments targeting the complement pathway. Its occurrence during pregnancy is uncommon and poses unique diagnostic and management challenges. Case Description: A 19-year-old primigravida at 19 wks 5 days of gestation, with a history of chronic ITP, asthma and hypertension, presented with back pain and palpitations. Physical examination was unrevealing. She had normal creatinine, but her urinalysis revealed proteinuria and microscopic hematuria. 24-hr urine protein was 2.7g. ANA, anti-dsDNA, SSA, and SSB antibodies, hepatitis B/C, and HIV negative. C4 was mildly low at 13 and C3 was normal. Kidney biopsy showed features consistent with C3GN. Complement studies showed activation of the alternative pathway with factor D deficiency. C5b-9 levels were within normal limits. Considering the preserved renal function and minimal inflammatory changes, immunosuppressive therapy was deferred initially. Patients’ proteinuria worsened once during pregnancy and tacrolimus was added, however it was discontinued within 3 days as patient did not tolerate it. Her proteinuria improved with blood pressure stabilization. Renasight genetic testing was performed, revealing that the patient is heterozygous for CFI gene and has c.1429+1G>C variant. This gene has both autosomal dominant (AD) and autosomal recessive (AR) inheritance and is associated with autosomal hemolytic uremic syndrome (AD), C3 glomerulopathy (AD) and Complement factor I deficiency (AR). Based on these results, patient is planned to be started on complement inhibitor treatment. Discussion: Previously only 5 cases have been reported in the literature that were managed conservatively during pregnancy. Newly diagnosed C3GN during pregnancy is exceedingly rare. Not much is known about this disease in pregnant individuals and prior cases of pregnancy were in patients who had a pre-existing diagnosis of C3GN. All seem to be done well during pregnancy, and it is not completely clear how pregnancy affects these patients. And data on optimal management strategies are sparse. Further research is needed to establish evidence-based guidelines for managing these patients.