Conservative Therapy in Fibrillary GN: A Four-Drug Kidney-Protective Approach

Asked by Gerald Appel, MD, about the role of nonspecific therapy, Andrew Bomback, MD, MPH, describes a growing number of patients with fibrillary glomerulonephritis (FGN) who have done well on conservative, nonimmunosuppressive treatment alone. The patients he feels most optimistic about, he notes, present with subnephrotic proteinuria and preserved or only mildly reduced GFR.

For these patients, Bomback uses a four-drug foundation: an ACE inhibitor or angiotensin receptor blocker; either a mineralocorticoid receptor antagonist or an endothelin receptor antagonist; an SGLT2 inhibitor; and, whenever possible, a GLP-1 receptor agonist. He tells patients that getting all four on board gives the kidney a strong foundational therapy against progression.

Bomback reports following several patients on this regimen, chosen for various reasons over immunosuppression, for 4 to 6 years, with nearly flat GFR decline and well-controlled proteinuria. He believes this expansive approach to conservative therapy makes sense even for more severe cases in which immunosuppression is used.

Appel agrees that this holds across many glomerular diseases where the best course is uncertain, but he raises a practical concern. Most of these agents lower blood pressure, and in IgA nephropathy clinicians have had difficulty combining them, sometimes struggling to add even two drugs in patients with low baseline blood pressure. He asks how Bomback sequences the medications.

Bomback explains that the challenge differs in FGN. His patients with FGN tend to be 10 to 20 years older than his patients with IgA nephropathy, who are typically younger, healthier, and more likely to start with low blood pressure. Because many patients with FGN arrive having read a grim prognosis online, he tells them he will start all four drugs at once rather than stagger them, to begin kidney protection as soon as possible, and he finds that most accept this strategy.

He agrees that endothelin receptor antagonists pose the greatest challenge because of relative hypotension, but notes this has been less of an issue in his older FGN population.