Pregnancy-Associated Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposition

Introduction: Proliferative glomerulonephritis with monoclonal immune deposits (PGNMID) is a rare form of monoclonal gammopathy of renal significance. Although it has been rarely reported at a young age, pregnancy-associated PGNMID represents a unique and rare clinal presentation that requires further understanding. Diagnosis of the condition is challenging as the clinical presentation and lab findings upon presentation are non-specific. Case Description: A 32-year-old female without any significant past medical history presented at 35 weeks of gestation with elevated blood pressure, a serum creatinine (S. Cr) of 0.58 mg/dL, and proteinuria of 2.8 grams/d. Serum creatinine increased to 1.2 mg/dL. A presumed diagnosis of pre-eclampsia was made, and vaginal delivery was induced at 37 weeks. Six weeks later, the patient was re-admitted with peripheral edema, uncontrolled hypertension, and acute kidney injury with a peak S. Cr of 4.5 mg/dL. Her 24-hour urine protein was 9.4 grams/d, and S. albumin was 1.7 gm/dL. A kidney biopsy showed IgG3-Lambda PGNMID with 80% cellular crescents. A detailed workup to identify pathological clone was negative, including serum protein electrophoresis, serum immunofixation, light chain ratio, peripheral blood flow cytometry, and bone marrow biopsy. Although kidney function improved with high-dose steroids initially with S. Cr of 1.4 mg/dL, the patient remains with persistent and severe nephrotic syndrome after 6 weeks of high-dose steroids (Prednisone 1mg/kg/d) and is being considered for empirical clone-directed therapy, pending insurance approval, at the time of writing this report. Discussion: The pathogenesis of PGNMID associated with pregnancy requires further understanding. Pregnancy is a state of dramatic immune modulation. The fetus/placenta unit could induce a maternal immune response, as part of the pro-inflammatory state or working as an alloantigen, producing nephrotoxic monoclonal protein resulting in PGNMID. Notably, while two previously reported cases improved after delivery, our patient failed to show clinical improvement with steroids after delivery and requires further treatment with clone-directed therapy. Thus, Pregnancy-associated PGNMID requires further understanding of pathophysiology, treatment options, and clinical prognosis.