Rituximab Rescue in Pregnancy: Triumph over Membranous Nephropathy

Abstract

A 18-year-old South Asian female developed nephrotic syndrome. Subsequent renal biopsy showed thickened glomerular basement membrane on light microscopy Periodic Acid Schiff (PAS) stain, with spikes on silver stain. Immunofluorescence showed IgG and C3 deposits while IgA, IgM and C1q were negative. This led to a diagnosis of Membranous Nephropathy (MN). As IgG4 staining was not introduced in the country at that time, and rest of the findings were typical for MN, patient was presumed to have Primary Membranous Nephropathy(PMN). She was treated with oral Prednisolone (60mg/day) along with Tacrolimus (0.05mg/kg/day). Prednisolone was successfully tapered off however attempting to taper tacrolimus, albeit prematurely, resulted in relapse twice. Her first presentation to us was at the age of 20. At that time, she was normotensive with pitting edema to her mid-shins. Urine routine examination showed 3+ proteinuria with no active sediment. She had a urine protein to creatinine Ratio (UPCR) of 5.8g/g, albumin of 2.47g/dl, LDL of 150 mg/dl and creatinine 0.5mg/dl. Phospholipase A2 Receptor Antibodies (anti-PLA2R) could not be checked due to unavailability of the assays at our setup at that time.  Further workup was ordered to exclude secondary causes of  MN. Hepatitis serology (for Hepatitis B and C) were negative. Complement levels were ordered that were normal. Erythrocyte Sedimentation Rate(ESR) was elevated at 35mm/hr. Her tacrolimus trough levels were suboptimal and her dose was optimized at 2mg twice a day. Ramipril 2.5mg twice a day was continued for proteinuria, furosemide 40 mg once a day for her pitting edema and rosuvastatin 20 mg at night for primary prevention of cardiovascular disease. She achieved partial clinical remission the following year with UPCR of 0.56g/g. After that, at the age of 21, she got married and wished to conceive. Ramipril was switched to Diltiazem. She was advised to wait till further reduction in proteinuria. She miscarried twice during this time, at the age of 22 and 24. At 25 years of age, she achieved complete clinical remission (UPCR of 0.06g/g).  At her next presentation to us, she was in her 5^th week of gestation with UPCR of 4.8g. Given that her proteinuria had increased before the 20^th week mark and her blood pressure was normal, the increase was attributed to relapse of her primary disease. Tacrolimus trough levels were confirmed to be optimal. Based on available evidence of Rituximab in pregnancy, potential risks and benefits were discussed with the patient and she subsequently opted for it. She was offered a low dose regime of Rituximab 100mg/week for 4 weeks which was administered at weeks 13, 14 16 and 17. Tacrolimus was continued at the same dose of 2mg twice a day. Her UPCR, albumin and LDL were followed closely throughout her pregnancy.

At 34 weeks of gestation, due to low Amniotic Fluid Index (AFI), labour was induced and a baby boy was born. He required admission in the nursery for a week due to prematurity. Post discharge, he remained stable. He is currently 2.5 years old, healthy and developing normally.

The mother was started on Valsartan 80mg once a day post-delivery and Diltiazem was discontinued. She achieved complete remission (UPCR 0.17g/g) 1-year post Rituximab administration and is in remission to date.