Review of the Clinical, Humanistic, and Economic Burden of Focal Segmental Glomerulosclerosis

Summary

A summary of the clinical, humanistic, and economic burden of FSGS¹

Background

Focal segmental glomerulosclerosis (FSGS) is a rare, progressive kidney condition defined by a histological pattern of glomerular and podocyte damage.^1,2 If unaddressed, podocyte damage can lead to proteinuria and progression to kidney failure.^1,3 FSGS can be classified as primary, secondary, genetic, or of undetermined cause, though all forms result in podocyte injury.^1,2

Incidence of primary FSGS in the US is estimated at 1.7 per 100,000 patient-years, with global estimates of approximately 0.2 to 2.5 per 100,000 per year.^1,4,5 Sparsentan recently became the first pharmacological intervention to be approved by the FDA for treatment in FSGS.^1,6

Aim

This review summarized the results of three systematic literature reviews (SLRs) investigating the clinical, humanistic, and economic burden of FSGS.¹

Approach

Several literature databases were systematically searched for relevant FSGS data on clinical, humanistic, and economic burden.⁷ All three SLRs included studies with patients of any age with primary or genetic FSGS.⁷

The clinical, humanistic, and economic SLRs included studies reporting efficacy/safety outcomes, studies reporting health-related quality of life (HRQoL), health state utility, or utility mapping data, and studies reporting cost, resource utilization, or economic evaluation data, respectively.⁷

Findings

FSGS is a serious clinical condition associated with significant morbidity¹

Historical cohorts of primary FSGS report 10-year renal survival of approximately 40% to 70%, with outcomes strongly dependent on achieving proteinuria remission.¹ Studies show that patients with FSGS who fail to achieve proteinuria remission are substantially more likely to progress to dialysis or transplant, and those with nephrotic-range proteinuria typically reach kidney failure within a few years if untreated.^1,8

Genetic forms of FSGS are generally resistant to immunosuppression and show comparably poor kidney survival rates.^1,9

Additionally, two studies observed that in primary FSGS patients, post-transplant recurrence is significant and linked to poorer graft survival.^1,9,10

Collectively, clinical data across FSGS populations demonstrate that FSGS is a serious condition with considerable associated morbidity.¹

FSGS impairs QoL for adult and pediatric patients and their caregivers¹

One study of adults with FSGS observed that, when evaluated with the 36-Item Short Form Survey, patients had lower mental and physical component scores than healthy adults, and lower mental component scores than patients with end-stage kidney disease (ESKD).^1,11

Similarly, a study in children with FSGS using the Pediatric QoL Inventory scale found poorer HRQoL and impaired emotional and school functioning compared to healthy populations.^1,12 Caregivers also reported reduced mental health scores.^1,12

Data from the Patient-Reported Outcomes Measurement Information System in adults and children with FSGS observed that achieving proteinuria remission was linked with better HRQoL in both groups, lower fatigue and better mental health in adults, and less pain and anxiety in children.^1,13

Taken together, FSGS diminished the HRQoL and mental well-being for both patients and their caregivers.¹

FSGS leads to greater costs and resource utilization¹

A retrospective study in the US showed that resource utilization and costs of those with FSGS exceeded those of matched controls, where outpatient care was the most frequently used category.^1,14 Both resource use and costs rose with disease severity.¹ Nephrotic-range proteinuria led to three-fold higher resource use and approximately 40% higher prescription costs than non–nephrotic-range proteinuria.^1,14

In addition to the direct costs of FSGS, work productivity was reduced in employed adults with FSGS.^1,12

Overall, FSGS drives high healthcare costs and resource utilization that escalate with disease severity, while also reducing patient productivity.¹

Treatment for FSGS focuses on reducing proteinuria to preserve kidney function¹

The 2021 Kidney Disease: Improving Global Outcomes (KDIGO) guideline recommends supportive care (including renin-angiotensin system blockade, blood-pressure control, and dietary salt restriction) for all adult patients with FSGS.^1,15

In April 2026, the FDA approved sparsentan, a non-immunosuppressive Dual Endothelin and Angiotensin Receptor Antagonist (DEARA), as the first pharmacological treatment for FSGS.^1,6 It was approved to reduce proteinuria in adult and pediatric patients aged 8 years and older with FSGS without nephrotic syndrome.^1,6 Nephrotic syndrome was defined as the concurrent presence of proteinuria >3.5 g/24 hours (adults) or urine protein-creatinine ratio (UPCR) >2.0 g/g (pediatric patients <18 years of age), serum albumin <3.0 g/dL, and edema at baseline.⁶

In the Phase 3 DUPLEX study, sparsentan led to a greater reduction in UPCR compared to irbesartan [-50.0% vs. -32.3%] at 108 weeks.^1,16 There was no significant difference observed in eGFR slope.^1,16 Safety of sparsentan was comparable to irbesartan.^1,16

Similar results were seen in the Phase 2 DUET trial and the interim analysis of the EPPIK study.¹

Key takeaway

SLR findings show that FSGS is associated with a clinical, humanistic, and economic burden, leading to poor long-term kidney outcomes, decreased HRQoL, and large financial impact.¹ Historical treatment options have been limited and often supportive in nature.^1,15 In April 2026, sparsentan became the first FDA-approved pharmacological treatment indicated to reduce proteinuria in patients with FSGS without nephrotic syndrome.^1,6

Footnotes

This study was funded by Travere Therapeutics.

DEARA, Dual Endothelin Angiotensin Receptor Antagonist; eGFR, estimated glomerular filtration rate; ESKD, end-stage kidney disease; FDA, Food and Drug Administration; FSGS, focal segmental glomerulosclerosis; HRQoL, health-related quality of life; KDIGO, Kidney Disease Improving Global Outcomes; SLR, systematic literature review; UPCR, urine protein-creatinine ratio.

MA-DS-26-0062 | July 2026