DNAJB9 in Fibrillary Glomerulonephritis: Diagnostic Biomarker, Putative Autoantigen, or Disease-Associated Scaffold?...

Fibrillary glomerulonephritis (FGN) is an uncommon glomerular deposition disease characterized by randomly oriented, nonbranching fibrils that are usually Congo-red-negative and larger than amyloid fibrils on electron microscopy. The discovery of DNAJ homolog subfamily B member 9 (DNAJB9) has transformed FGN from a primarily ultrastructural diagnosis into a molecularly recognizable disease. However, the pathogenic significance of DNAJB9 remains unresolved: it may represent a highly specific biomarker, a putative autoantigen, a chaperone-associated scaffold, or a marker of disturbed protein quality control. We report two patients with positive glomerular DNAJB9 staining and markedly divergent clinical phenotypes. The first patient, a 58-year-old man, presented with severe acute kidney injury, nephritic urinary sediment, severe hypertension, crescentic immune-complex glomerulonephritis, and dialysis-requiring kidney failure. Electron microscopy and IgG subclass staining were unavailable; therefore, the findings were interpreted as probable rather than definitive DNAJB9-positive FGN. Diagnostic and causal interpretation was further complicated by concurrent Klebsiella pneumoniae urinary tract infection, mild bilateral hydronephrosis, acute tubulointerstitial injury, and severe hypertension. Kidney function did not recover despite glucocorticoids and cyclophosphamide, but the adverse outcome and treatment response cannot be attributed to FGN alone. The second patient, a 66-year-old woman, presented with chronic proteinuria, preserved kidney function, inactive urinary sediment, and lupus-like serologic findings. Electron microscopy demonstrated randomly arranged, nonbranching 13-19 nm fibrils, and DNAJB9 staining confirmed FGN. She was managed with angiotensin receptor blockade and dapagliflozin, with reduction of proteinuria to below 1 g/day. Together with previously published cohorts, these cases illustrate the diagnostic value of DNAJB9 staining and the potential clinicopathologic heterogeneity of FGN. However, Case 1 should be considered a clinically confounded, hypothesis-generating example and not definitive evidence that FGN alone caused the crescentic presentation, dialysis dependence, or lack of response to immunosuppression.