Corticosteroids, RAS Inhibitors, or Sparsentan First for FSGS?

"Corticosteroids, RAS Inhibitors, or Sparsentan First for FSGS?" takes up the question of where older standbys still belong now that sparsentan has entered the treatment landscape.

Dr. Campbell asks what role remains for corticosteroids and RAS inhibitors now that sparsentan has FDA approval for FSGS. Dr. Trachtman notes clinicians have known for two to three decades that roughly a third of patients respond meaningfully to corticosteroids, and a similar proportion see substantial proteinuria reduction on calcineurin inhibitors, while ACE inhibitors and ARBs have long served as a foundational, near-universal add-on. He suggests sparsentan may begin to displace RAS inhibitors specifically, since it capitalizes on the interacting biology between endothelin and angiotensin signaling, two systems known to reinforce glomerular injury together. His expectation is that sparsentan could become a reasonable first-line option to lower proteinuria, with corticosteroids or calcineurin inhibitors reserved for patients whose response proves insufficient. He is careful to note this doesn't diminish the value of immunosuppression, which addresses a distinct treatment need for patients who require it.

Asked how he counsels patients already on older therapies, Dr. Trachtman acknowledges the question is complicated, since tolerance for residual proteinuria varies by disease: patients with membranous nephropathy tend to tolerate higher levels without as grim a prognosis, while emerging international data in IgA nephropathy suggests there may be no truly safe proteinuria level at all. He expects FSGS research will eventually clarify how low proteinuria must fall to meaningfully change the disease's natural history, and how to combine older agents with sparsentan once that's better understood. On the practical logistics of switching, Dr. Trachtman predicts most clinicians will simply replace an ACE inhibitor or ARB outright with sparsentan, since patients already tolerate that mechanism without kidney function decline. He expects monitoring won't differ substantially from current practice, though the combined endothelin receptor blockade warrants continued vigilance to ensure no harm comes to the patient during the transition.

Up next, in "Inside the DUPLEX Trial: FSGS Design, Endpoints, and Exclusions," the experts dig into the DUPLEX trial's design, from its enrollment criteria to the endpoints that shaped its outcome.