Immunoglobulin-Negative DNAJB9-Associated Fibrillary Glomerulonephritis: A Report of 9 Cases.

Fibrillary glomerulonephritis (FGN) was previously defined by glomerular deposition of haphazardly oriented fibrils that stain with antisera to immunoglobulins but do not stain with Congo red. We report what is to our knowledge the first series of immunoglobulin-negative FGN, consisting of 9 adults (7 women and 2 men) with a mean age at diagnosis of 66 years. Patients presented with proteinuria (100%; mean protein excretion, 3g/d), hematuria (100%), and elevated serum creatinine level (100%). Comorbid conditions included carcinoma in 3 and hepatitis C virus infection in 2; no patient had hypocomplementemia or monoclonal gammopathy. Histologically, glomeruli were positive for DNAJB9, showed mostly mild mesangial hypercellularity and/or sclerosis, and were negative for immunoglobulins by immunofluorescence on frozen and paraffin tissue. Ultrastructurally, randomly oriented fibrils measuring 13 to 20nm in diameter were seen intermingling with mesangial matrix in all and infiltrating glomerular basement membranes in 5. On follow-up (mean duration, 21 months), 2 had disease remission, 4 had persistently elevated serum creatinine levels and proteinuria, and 3 required kidney replacement therapy. Thus, rare cases of FGN are not associated with glomerular immunoglobulin deposition, and the diagnosis of FGN in these cases can be confirmed by DNAJB9 immunostaining. Pathogenesis remains to be elucidated.

Relapse or worsening of nephrotic syndrome in idiopathic membranous nephropathy can occur even though the glomerular immune deposits have been eradicated.

BACKGROUND: Relapse or worsening of nephrotic syndrome (NS) in idiopathic membranous nephropathy (IMN) is generally assumed to be due to recurrent disease. Here we document that often that may not be the case. SUBJECTS AND METHODS: This is a prospective study of 7 consecutive IMN patients whose renal status improved, then worsened after completing a course of immunosuppressive therapy. Each underwent detailed testing and repeat kidney biopsy. RESULTS: In 4 patients (group A), the biopsy showed recurrent IMN (fresh subepithelial deposits). Immunosuppressive therapy was begun. In the other 3 patients (group B), the biopsy showed that the deposits had been eradicated. However, the glomerular basement membrane (GBM) was thickened and vacuolated. Immunosuppressive therapy was withheld. Groups A and B were comparable except that group B had very high intakes of salt and protein, based on 24-hour urine testing. Reducing their high salt intake sharply lowered proteinuria to the subnephrotic range and serum creatinine stabilized. CONCLUSION: This work is the first to demonstrate that relapse/worsening of NS can occur in IMN even though the GBM deposits have been eradicated. High salt and protein intake in combination with thickened and vacuolated GBM appears to be the mechanism.