Membranous nephropathy in patients with HIV: a report of 11 cases

Abstract

Background: Membranous nephropathy (MN) has been recognized to occur in patients with human immunodeficiency virus (HIV) infection since the beginning of the HIV epidemic. The prevalence of phospholipase A2 receptor (PLA2R)-associated MN in this group has not been well studied.

Methods: We conducted a retrospective review of electronic pathology databases at three institutions to identify patients with MN and known HIV at the time of renal biopsy. Patients with comorbidities and coinfections known to be independently associated with MN were excluded.

Results: We identified 11 HIV-positive patients with biopsy-confirmed MN meeting inclusion and exclusion criteria. Patient ages ranged from 39 to 66 years old, and 10 of 11 patients (91%) were male. The majority of patients presented with nephrotic-range proteinuria, were on anti-retroviral therapy at the time of biopsy and had low or undetectable HIV viral loads. Biopsies from 5 of 10 (50%) patients demonstrated capillary wall staining for PLA2R. Measurement of serum anti-PLA2R antibodies was performed in three patients, one of whom had positive anti-PLA2R antibody titers. Follow-up data was available on 10 of 11 patients (median length of follow-up: 44 months; range: 4-145 months). All patients were maintained on anti-retroviral therapy (ARV) and 5 patients (52%) received concomitant immunosuppressive regimens. Three patients developed end-stage renal disease (ESRD) during the follow-up period.

Conclusions: MN in the setting of HIV is often identified in the setting of an undetectable viral loads, and similar to other chronic viral infection-associated MNs, ~ 50% of cases demonstrate tissue reactivity with PLA2R antigen, which may be seen without corresponding anti-PLA2R serum antibodies.

Fig. 1

Biopsy Findings in patients with HIV infection and membranous nephropathy (MN). A-C: Early MN A) Well preserved glomerulus with mildly thickened basement membranes (PAS, × 400). B) Diffuse granular capillary wall staining with IgG. C) Subepithelial electron dense deposits (arrows) with associated basement membrane spikes (× 10,000; Patient 5). D-F: Chronic MN with extensive tubular atrophy and hypertensive arteriosclerosis. D) Glomerulus with basement membrane spikes (JMS, × 400). E) Diffuse granular capillary wall staining with PLA2R immunofluorescence. F) Discrete capillary wall deposits with PLA2R immunohistochemistry. (Patient 6). G-I: MN with co-existent HIVAN-like features. G) Prominent interstitial inflammation and intratubular neutrophils (arrows) in a biopsy with segmental MN (not shown) (PAS, × 200). H) Glomerulus with epithelial cell proliferation and segmental capillary wall collapse (Toluidine-Blue, × 400). I) Segmental subepithelial and intramembranous electron dense deposits (arrows). Mesangial sclerosis attributed to co-existent early diabetic nephropathy. Focal mesangial deposits were also present (not shown) (× 2700; Patient 2). J-M: MN with chronic active tubulointerstitial nephritis. J) Interstitial edema and inflammation associated with tubular injury. Glomerulus has thickened basement membranes (arrow) (H&E, × 200). K) Diffuse granular capillary wall immunofluorescence staining with IgG4 subclass. L: Similar staining with PLA2R immunofluorescence. M) Intramembranous deposits with electron lucent areas (arrows) (stage III-IV MN deposits; Patient 3)

Fig. 2

Immunofluorescence microscopy findings in 11 patients with HIV and MN. Intensity of staining was graded on a scale of 0–3, and color coded in the figure from light blue (0) to dark blue (3). A value of 0.5 refers to “trace” staining. All numbers reflect the intensity of granular capillary wall staining, unless otherwise specified. *Refers to granular mesangial and segmental capillary wall staining. Abbreviations: NG: No glomeruli present for evaluation; NP: Not performed