Membranous Nephropathy with Microspherule Deposits

Introduction: Electron microscopy (EM) findings of microspherule deposits in the glomerular basement membrane (GBM) and mesangium occur in a small proportion of membranous nephropathy (MN) cases. We report a case of microspherical structures in immune deposits by EM in a patient with MN, autoimmune hepatitis (AIH) and prior hepatitis B (Hep B) exposure. Case Description: 57-year-old female with AIH presented for evaluation of urine protein to creatinine ratio of 8000 mg/g and urine albumin to creatinine ratio 4206 mg/g. Lab work revealed serum creatinine 0.68 mg/dL, albumin 2.7 mg/dL. Hep B serologies were indicative of past Hep B exposure without previous treatment. Hepatitis C, Syphilis, HIV serologies were negative. Autoimmune work up showed normal C3 and C4 levels, negative anti-PLA2R and anti-THSD7A, negative double stranded DNA, positive ANA (> 1:640) and anti-smooth muscle antibody (1:1280). On kidney biopsy, glomeruli had diffuse global thickening of capillary walls. Silver stain demonstrated numerous GBM craters (pinholes). Immunofluorescence microscopy showed glomerular diffuse global granular capillary wall staining for IgG 4+, IgA 2-3+, IgM 2+, C3 2+, and kappa and lambda light chains 3+; with no staining for C1q. On EM, microspherical structures were noted in immune deposits (Fig 1). A possible cause of the MN with microspherular deposits is AIH. She received conservative treatment for proteinuria and was started on azathioprine and prednisone for AIH, resulting in partial remission of MN. The focus remains on achieving AIH remission to manage her kidney disease Discussion: The presence of microspherical structures on EM has been previously associated with MN due to underlying infections, autoimmune disorders, and malignancies. Clinicians should consider a thorough work up for secondary causes when micropherules are identified in MN immune deposits.