PLA2R related primary membranous nephropathy in a hepatitis C positive patient

A 58-year-old non-diabetic female with history of hypertension presented with swelling of both lower limbs and facial puffiness of 5-month duration. Evaluation revealed nephrotic syndrome (proteinuria 2.8 g/day, bland urinary sediment, serum albumin 1.6 g/dL) and normal kidney function (serum creatinine 0.63 mg/dL). The kidney biopsy was suggestive of membranous nephropathy with enhanced staining for M-type phospholipase A2 receptor (PLA2R). Anti-hepatitis C virus (HCV) antibody was positive, with 38,90,243 IU/mL of HCV RNA (genotype 3). The serum antibody to PLA2R (aPLA2R) was 236 RU/mL. The patient was started on telmisartan, atorvastatin, diuretics, warfarin, sofosbuvir and ribavirin. The HCV RNA became undetectable (< 50 IU/mL) at 2 months. The aPLA2R after 2 months of antiviral therapy came down to 4.67 RU/mL. However, the nephrotic syndrome persisted. A repeat aPLA2R 9 months after initial presentation showed a rise (117.62 RU/mL). At this time, a diagnosis of aPLA2R related MN was made, cyclical cyclophosphamide and steroids were started and the patient achieved complete clinical remission. The proteinuria became undetectable; serum albumin was 3.69 g/dL and repeat aPLA2R 0.0019 RU/mL 8 months after starting the therapy. The patient remains in remission after 5 months of stopping immunosuppressive therapy, and the HCV viral load remains undetectable (13 months after stopping antivirals). The present case highlights the fact that not all MN in hepatitis C positive patients are virus related. Larsen et al. reported enhanced staining for PLA2R in 64% of HCV associated MN. The studies describing PLA2R in MN with hepatitis B and/or C infection are limited by lack of sequential antibody monitoring after treating infection. In the index case, the NS failed to abate despite successful treatment of hepatitis C infection. Interestingly, the aPLA2R came down during the anti-viral treatment but reappeared, perhaps due to the serum-glomerular dynamics, which has been well described in the past. The clinical and serological remission with immunosuppressive treatment clearly demonstrates the primary nature of the disease. Alternatively, the virus could be acting as a trigger for producing antibodies.