U.S. — Sparsentan (Filspari) received approval this year for the treatment of focal segmental glomerulosclerosis (FSGS). The medication is indicated to reduce proteinuria in patients aged 8 years and older who do not have nephrotic syndrome, defined as proteinuria over 3.5 g/day.

FSGS is a kidney disease marked by scarring of the glomeruli, which can lead to chronic proteinuria and irreversible damage, frequently resulting in kidney failure. The disease has no known cure and is estimated to affect more than 40,000 people in the U.S. Kristin Meliambro, MD, described FSGS as a "difficult diagnosis to treat and one that is both frustrating for patient and nephrologists." A central goal of FSGS treatment involves reducing proteinuria.

FSGS treatments are broadly categorized into immunosuppressive and non-immunosuppressive agents. Non-immunosuppressive options, including SGLT2 inhibitors and renin-angiotensin-aldosterone system (RAAS) blockade through ACE inhibitors, ARBs, and aldosterone antagonists, help reduce proteinuria and lower hydrostatic pressure inside the glomeruli. According to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, immunosuppressant treatments, such as high-dose oral glucocorticoids and calcineurin inhibitors, are recommended as first-line therapies for primary FSGS. However, KDIGO guidelines advise against immunosuppression for patients with secondary or undetermined causes of FSGS. A 2016 review indicated that response rates for first-line treatment using daily oral prednisolone ranged from 50% to 68.8%.

Sparsentan operates with a dual mechanism of action, targeting both endothelin A and angiotensin II receptors. Margaret De Oliveira, MD, stated she is "shifting my first-line management strategy to include sparsentan, given the benefit in proteinuria reduction." Dr. De Oliveira added that "there are so many new medications in the pipeline and available now to help slow down the progression of chronic kidney disease from many different etiologies." She also noted, "I really think this is a renaissance period for our specialty and am excited to see what happens in the next few years."

Beyond existing treatments, other investigational drugs are under development. Inaxaplin, an investigational agent, targets APOL1-mediated kidney disease by inhibiting APOL1 function. A small phase II trial showed positive findings for inaxaplin in patients with biopsy-proven FSGS and two APOL1 mutations. Additionally, the investigational oral drug DMX-200 is currently in phase III testing. DMX-200, administered alongside standard ARB therapy, blocks the CCR2 receptor to reduce inflammation and demonstrated proteinuria reduction in a 16-week phase II trial. Meliambro said, "APOL1 inhibitors and CCR2 pathway inhibitors are great examples of this active movement and have the potential to really expand the treatment arsenal for FSGS patients and meaningfully alter their disease course."

Lifestyle modifications are also part of FSGS management. Every FSGS patient should adhere to a low-salt diet, limiting daily salt intake to under 2 grams, as recommended by KDIGO guidelines. Abbal Koirala, MD, noted, "It's not just to control hypertension or edema: the salt itself increases pressure in the glomeruli and causes a transient rise in proteinuria." Dr. Koirala also stated, "Obesity increases blood flow to the glomeruli and increases progression of kidney disease, independent of diabetes." Additionally, FSGS patients should limit excess protein intake to 0.6 to 0.8 g/kg per day, ensure diabetes is well-controlled, follow a low-cholesterol diet, and cease smoking.