Immunosuppression in Fibrillary GN: Early Biopsy and Histology-Guided Treatment

Gerald Appel, MD, opens the segment by observing that patients with fibrillary glomerulonephritis (FGN) who present with lower proteinuria and better GFR tend to do better, a pattern that mirrors lupus nephritis and IgA nephropathy. He argues that this makes early kidney biopsy essential, particularly now that DNAJB9 staining is highly specific for FGN and excludes immunotactoid glomerulonephritis and other entities that were once grouped together and caused confusion.

Appel then asks Andrew Bomback, MD, MPH, where he draws the line between immunomodulatory and nonspecific therapy for a newly diagnosed patient. Bomback reserves immunosuppression for patients who are heavily nephrotic or clearly progressing, with GFR declining faster than expected. Choosing a regimen, he acknowledges, is still largely uncharted territory, but the FACT trial offers some guidance with two options: ACTH alone, which produced a strong antiproteinuric response in some patients, or ACTH combined with tacrolimus, which also worked for some.

Bomback turns the question back to Appel, asking whether he favors monotherapy or combination immunosuppression. Appel describes an individualized approach that starts with light microscopy. He acknowledges that his view may not be universally shared, but he finds that the light microscopy pattern can be very helpful in guiding therapy. Crescentic disease, with 40% to 50% crescents, is always treated vigorously, and he recalls that the very first FGN case he saw had this pattern, at a time when Dr Pirani described the deposits as noncongophilic amyloid-like fibrils.

Appel explains that he treats crescentic FGN as a crescentic glomerulonephritis and considers membranous-type regimens for a membranous pattern. For the more common mesangioproliferative and membranoproliferative patterns, he leans toward a more vigorous, multidrug approach. Nonspecific therapy aimed at lowering proteinuria remains part of that foundation, he adds, with proteinuria serving as the marker of response.

He adds that the question of what to do after a fixed course of therapy ends remains unanswered, noting that for some glomerular diseases clinicians continue rituximab every 6 months while heavy proteinuria persists.