Complement Dysregulation in Preeclampsia: The Role of Kidney Biopsy

Introduction: New-onset Systemic Lupus Erythematosus (SLE) in pregnancy is a well-recognized entity that has overlapping features with Preeclampsia. We describe a patient with pre-eclampsia who presented with severe nephrotic syndrome, 16 g proteinuria, and positive Anti-DNA Ab. Case Description: A 29-year-old G3P2 female with no medical history presented at 25+3 weeks gestation with hypertension 150/90 and apparent volume overload. Hb 10.7 g/dL, platelets 240 k/mm3 and creatinine (sCr) 0.7 mg/dL. Workup revealed microscopic hematuria, Tp/cr ratio of 3.5 g/dl, hyperkalemia, LDH 449 IU/ml, haptoglobin 69 g/dl, normal transaminases, normal ADAMST13 73%, negative ANA, and positive anti-dsDNA 14. C3 was normal 107 mg/dL with negative ANCA, cardiolipin, PLA2R, and autoimmune workup. She had a nadir platelet count of 120 k/mm3, complement C4 of 5 mg/dL, proteinuria increased to 16 g/g, and sCr to 1.3 mg/dL. There was no evidence of HELLP. A diagnosis of lupus nephritis was made due to the presence of Anti-dsDNA, low C4, and proteinuria, and she received pulse dose steroids for 3 days. Complement Factors H, I, B, complement I Ab, and CD46 expression were all normal however genetic testing showed a Complement Factor H (CFH) variant. A kidney biopsy showed glomerular endothelial swelling & no immune complexes by IF or EM, as well as thrombotic microangiopathy (TMA) consistent with pre-eclampsia. No features of lupus nephritis were otherwise identified. An urgent C-section was performed. Patient had rapid resolution of edema and proteinuria with complete recovery of renal function. Discussion: Defective complement regulation allows for placental damage and generalized endothelial activation that can be seen in pre-eclampsia. In our case, genetic testing confirmed a CFH variant, supporting the patient’s predisposition to preeclampsia. New-onset lupus and lupus nephritis in pregnancy closely mimic findings of pre-eclampsia, as seen in our case, where the patient had positive Ant-dsDNA Ab, low complement C4, and nephrotic range proteinuria. Our case highlights the potential role for kidney biopsy in patients with features suggestive of lupus nephritis as, in this case, the biopsy findings consistent with pre-eclampsia rather than lupus nephritis prompted appropriate treatment with urgent C-section, with resolution of pre-eclampsia and avoidance of unnecessary immunosuppression in pregnancy.