How You Lower Proteinuria in IgAN: Immunologic vs Hemodynamic

In "How You Lower Proteinuria in IgAN: Immunologic vs Hemodynamic," the panel draws a distinction that reshapes treatment goals.

Dr. Parikh reiterates a point of agreement between Dr. Rovin and Dr. Fervenza. New therapies can lower proteinuria without eliminating it while stabilizing GFR, at least with B-cell drugs. Dr. Rovin calls that stabilization amazing. He contrasts the endothelin antagonists, which reduce proteinuria with only a modest GFR effect, against B-cell drugs with a major effect on GFR slope. He argues the way proteinuria is reduced is the important aspect of treatment. Dr. Rovin frames it as a soundbite: if two drugs lower proteinuria equally but only one stabilizes GFR, he wants that drug. He says treating the disease's immunology slows progression. Dr. Mehdi offers a challenging patient scenario to illustrate the point. He describes younger patients in their thirties and forties with hematuria and roughly one gram of proteinuria. On non-immunomodulatory therapy, their proteinuria falls to 0.3 grams, yet hematuria persists. When rebiopsied two or three years later, their glomerulosclerosis has climbed from 10% to 35%. Dr. Rovin confirms he has seen exactly this pattern. Dr. Mehdi notes this population has been excluded from clinical trials, even though the biology argues for immunologic treatment. Dr. Parikh summarizes for the audience that the CKD-directed therapies still matter. He lists RAS blockade, SGLT2 inhibitors, MRAs, and endothelin antagonists as important for maladaptive kidney processes. But reducing proteinuria that way, he stresses, is not the same as reducing inflammation immunologically. He remains worried about patients left with persistent hematuria and residual proteinuria, because ongoing glomerular inflammation predicts progression.

Our next episode, "IgAN Pathogenesis and the Rationale for Complement Inhibition," turns to Dr. Rovin for an overview of the multi-hit pathogenesis and the first targeted therapy, complement inhibition.