Second-Line Therapy in Fibrillary GN: Secondary Causes and Rituximab Data

Asked by Andrew Bomback, MD, MPH, how he approaches second-line therapy when a patient with fibrillary glomerulonephritis (FGN) does not respond to initial treatment, Gerald Appel, MD, begins by stressing the need to exclude secondary causes. Although secondary disease is much less common in FGN than in immunotactoid glomerulonephritis, some patients have an underlying tumor, a monoclonal gammopathy, or hepatitis C infection, and those possibilities should be ruled out first.

From there, Appel describes the role of nonspecific antiproteinuric therapy. Some clinicians, he notes, believe that patients with proteinuria below 2 to 3 g should receive only nonspecific therapy, including ACE inhibitors or angiotensin receptor blockers and, in the modern era, potentially SGLT2 inhibitors or an endothelin receptor antagonist. Whether proteinuria reduction achieved this way yields the same results as reduction with ACTH or rituximab remains unclear, he adds.

The conversation turns to rituximab, which has been examined in several FGN studies. Bomback notes that one of the larger series, frequently cited as evidence that rituximab may be effective in FGN, comes from their own group at Columbia, and that both he and Appel are authors. A subset of patients in that series responded, with proteinuria reduction and slowed progression.

Bomback highlights a finding he believes is often overlooked. The patients who responded best to rituximab also had the strongest predictors of response to any immunosuppressive therapy, namely the best GFR and the lowest proteinuria at the start of treatment. Those who fared worst had the lowest GFR and the highest proteinuria. He suggests that the responders likely sat on the milder end of the FGN spectrum and may have done well with conservative therapy alone.

For that reason, Bomback explains, he does not currently use rituximab as a main therapy for FGN, in part because the role of B-cell biology in FGN pathogenesis remains uncertain.