Membranous nephropathy associated with viral infection

Abstract

Background: Membranous nephropathy (MN) can be associated with hepatitis infection and less commonly with human immunodeficiency virus (HIV) infection. The significance of anti-phospholipase A2 receptor (PLA2R) and anti-thrombospondin type 1 domain-containing 7A (THSD7A) antibodies in this setting is unclear.

Methods: We describe the clinical, histopathological and outcome data of 19 patients with MN and hepatitis B virus (HBV), hepatitis C virus (HCV) or HIV infection identified through our renal biopsy database and the association with anti-PLA2R antibodies and anti-THSD7A antibodies.

Results: The cohort consisted of 19 patients, 8 male and 11 female, with a median age of 42 years (range 23-74). HBV infection was found in six cases, HCV in four and HIV in nine (two HIV patients had HBV co-infection and one HCV co-infection). PLA2R staining on biopsy was positive in 10/19 patients: 4 with HBV-MN, 3 with HCV-MN and 3 with HIV-MN and circulating anti-PLA2R antibodies were detected in 7/10 cases. THSD7A staining on biopsy was positive in three PLA2R-negative cases, one with HBV-MN and two with HIV-MN. Mean proteinuria was higher in the PLA2R-positive group and the median urinary protein:creatinine ratio (uPCR) was 963 mg/mmol (range 22-2406) compared with the PLA2R-negative group [median uPCR 548 mg/mmol (range 65-1898); P = 0.18 Mann-Whitney]. Spontaneous remission occurred in 6/19 patients and after-treatment remission occurred in 7/11 patients. Renal function was preserved in all but two patients who required haemodialysis 2 and 11 years from diagnosis.

Conclusions: We describe a cohort of patients with MN associated with viral infection, including rare cases of HIV-MN with PLA2R and THSD7A positivity. The mechanism of coincidental or viral-related MN needs to be investigated further.

Keywords: HIV; PLA2R; THSD7A; hepatitis B; hepatitis C; membranous nephropathy.

FIGURE 1

Renal biopsy of Case 15 (MN, HIV and HBV): (A) haematoxylin and eosin staining shows thickened glomerular capillary walls; (B) silver staining demonstrates characteristic spikes and holes along the capillary wall, shown in the inset; (C) IgG staining shows granular staining along the capillary wall; (D) IF for PLA2R shows granular staining along the capillary walls; (E) EM shows typical EDD in the subepithelial area and (F) THSD7A staining of Case 14 (HIN-MN) shows granular staining along the capillary walls.

FIGURE 2

Serum anti-PLA2R antibody levels in seven PLA2R-positive patients at the time of biopsy and 3-, 6- and 12-months post-biopsy. The increase in antibody titre in Case 9 occurred at the time of relapse.