DNA J homolog subfamily B member 9 and other advances in fibrillary glomerulonephritis

Purpose of review Fibrillary glomerulonephritis (FGN) involves ∼1% of native kidney biopsies and is characterized by glomerular deposition of fibrils larger than amyloid (12–24 nm diameter) composed of polyclonal immunoglobulin G (IgG). The recent discovery of DNA J homolog subfamily B member 9 (DNAJB9) in FGN glomerular deposits has contributed a specific and sensitive biomarker, informing morphologic classification and pathogenesis. This review will consider contemporary FGN incidence and genetics, pathogenesis, (lack of) paraprotein association, variants, treatment, and transplantation. Recent findings DNAJB9 tissue assays have enabled the identification of morphologic variants and improved classification of fibrillary-like glomerular diseases. Together with paraffin immunofluorescence and IgG subclass studies, these have established that FGN is only rarely monoclonal and these patients usually do not have an monoclonal gammopathy. The discovery of DNAJB9 opens new avenues of investigation into FGN pathogenesis, especially those of the unfolded protein response. Treatment for FGN remains empiric, with some encouraging data on rituximab-based therapy. Transplantation is a good option for patients progressing to end-stage kidney disease. Summary Advances building on the discovery of DNAJB9 in FGN should lead to long-term evolution in targeted treatment and outcome of this glomerular disease.