Anti-brush Border Antibody Disease with Segmental Membranous Nephropathy and Acute Tubular Injury in a Patient with Severe Diabetic Nephropathy

Introduction: Autoantibody directed to the low-density lipoprotein receptor related protein 2 (LRP2), also known as megalin, is a newly recognized cause of human autoimmune tubular injury. This entity has been termed antibrush border antibody (ABBA) disease or anti-LRP2 nephropathy. LRP2 plays an important role in proximal tubular endocytosis of albumin and other molecules. Case Description: A 64-year-old male with longstanding diabetes and recurrent AKIs on CKD4A3 presented with symptomatic volume overload and oliguric AKI. He was hypoalbuminemic [Sr albumin 1.5 g/dL] and had high grade proteinuria [UPCR ~ 12.5 g/g] on admission. Extensive serological workup was negative. Kidney biopsy revealed severe diabetes related kidney injury including mesangiolysis and microaneurysmal ruptures, segmental membranous nephropathy [IgG and light chains being 2+], and moderate acute tubular injury. Diffuse, homogenous appearing electron-dense deposits were noted along the TBMs. NELL-1 staining was negative along the GBM; LRP2 staining was positive along the TBM as well as segmentally in the glomeruli [membranous pattern] and along the Bowman's capsule. Patient continues to be dialysis dependent as of now. Immunosuppression was not started given his tenous overall condition. Discussion: ABBA disease is extremely rare seen in 0.05% of all kidney biopsies. It most commonly afflicts elderly White males; 41% cases have concomitant monoclonal gammopathies. Its co-occurance with severe diabetic nephroapthy is not well ascribed. Acute tubular injury, granular TBM deposits in the proximal tubule, and segmental deposits in the subepithelial region and Bowman's capsule [seen in 80%] are charecteristic. Confirmation warrants positive IF staining for LRP2 within TBM deposits or serologic confirmation of anti-LRP2 antibodies by indirect IF performed on normal human kidney. Prognosis is guarded with 53% progressing to ESKD. Immunosuppression may be warranted in most cases. Our case highlights the importance of considering ABBA disease in the differential when diffuse TBM injury is noted.