Rituximab Responsive Relapsing Fibrillary Glomerulonephritis

Introduction: Fibrillary glomerulonephritis (FGN) is seen in 1% of kidney biopsies and is characterized by glomerular deposition of infiltrative fibrils larger than amyloid composed of polytypic IgG lacking Congo red (CR) reactivity. DnaJ homolog subfamily B member 9 (DNAJB9) also known as endoplasmic reticulum-localized DnaJ 4 was discovered is a highly sensitive and specific biomarker. Upto 50% progress to ESKD within a few years of biopsy but the disease course remains highly variable as some patients with sub-nephrotic proteinuria and well-preserved kidney function can have more of a chronic, smoldering course over time. Case Description: 63-year-old female with past medical history significant for arterial hypertension, morbid obesity, & prediabetes presented with microscopic hematuria & proteinuria. Cr 1.5 mg/dL, eGFR 39 mL/min, Sr albumin 4 g/dl, UPCR 8962 mg/g. Urine microscopy: acanthocyturia & RBC casts. Comprehensive serological workup negative. Kidney biopsy - LM: Moderately expanded mesangium with mild hypercellularity. Capillary basement membranes showed focal & segmental splitting due to the extension of similar material along the capillary loops; 5% IFTA. IF: 2+ smudgy, predominantly mesangial and rare capillary loop staining for IgG, C3 [1-2+], kappa = lambda = 2-3+. EM: Moderately increased mesangial matrix with segmental nodularity, containing randomly arranged, nonbranching, fibrillary deposits, 9-18 nm in diameter. No immune complex deposits or punctate amorphous deposits were identified. CR stain was negative. DNAJB9 IHC stain positive in glomeruli. Patient received 2 courses of Rituximab [each course with 2 doses of 1g spread 14 days apart]. During last follow up, Sr Cr and albumin were normal with UPCR having reduced to 2638 mg/dL. Further Rituximab administration is being based on B-cell reconstitution. Discussion: There is no standard-of-care treatment for FGN. Rituximab may be the most promising treatment for progressive FGN. In the first prospective clinical trial of rituximab in 11 patients with FGN, investigators observed no significant change in the eGFR at 12 months. At 1 year, there was an overall ∼50% reduction in proteinuria; 3 patients experienced a partial response. Neither treatment nor disease remission status affected DNAJB9 serum levels. Our case highlights the utility of considering use of repeated doses of Rituximab for a select subset of FGN patients.