Video
RKD Show: Introduction to FSGS Ft. Dr. Howard Trachtman
Explore the complex nature of FSGS
What is it about?
Focal segmental glomerulosclerosis (FSGS) is a rare, progressive kidney condition characterized by a histological pattern of glomerular and podocyte injury that leads to proteinuria and often concomitant nephrotic syndrome.¹ ² It is one of the leading causes of kidney failure (KF).³
FSGS is classified based on proteinuria, underlying etiology (i.e. primary, secondary, genetic, or undetermined causes), and histologic patterns observed from a kidney biopsy.¹ ⁴ All forms of FSGS, regardless of their etiology, are podocytopathies that share a common glomerular lesion mediated by podocyte injury.¹ ²
The pathogenesis of FSGS is multifactorial and involves various mediators and pathways.⁵ Endothelin-1 (ET-1) and angiotensin II (Ang II) are key disease mediators of podocyte damage in FSGS.⁶ They act in tandem via the endothelin type A and angiotensin subtype 1 receptors (ETAR and AT₁R, respectively) to amplify ongoing podocyte injury and depletion, ultimately worsening proteinuria and driving progression to KF.⁶
With the current standard of care, treatment response is often limited in FSGS, leading to a high clinical, economic, and humanistic burden.⁷
Why is it important?
Although FSGS is rare, it has a substantial impact on patients and the healthcare system.⁷ Between 2008 and 2018, KF caused by FSGS affected approximately 87.6 per one million Americans.⁷ Elevated proteinuria and progression to KF in FSGS is associated with worse clinical outcomes, including an increased risk of cardiovascular disease and all-cause mortality.⁸
Patients who progress to KF may require hospitalization as well as therapies and interventions such as dialysis and kidney transplantation, resulting in high healthcare costs.⁷ An analysis of data from the US Renal Data System (USRDS) found that patients using Medicare who were hospitalized accrued a mean total of $68,384 in annual healthcare costs; however, the true costs are likely much higher.⁷
FSGS also negatively impacts quality of life, with patients experiencing painful physical symptoms, psychological impairment, and decreased work productivity.⁷ ⁹ ¹⁰ Patients with FSGS have been found to experience increased anxiety, depression, and impairment in work productivity as compared to those without FSGS.⁹
Despite the high clinical, economic, and humanistic burden, there are currently no FDA-approved targeted therapies to treat FSGS.¹¹ With the current standard of care, few patients achieve complete remission of proteinuria, and most remain at high risk of rapid progression to KF.¹¹
To reduce the burden of FSGS, there is a need for⁷ ⁹ ¹² ¹³:
- Early diagnosis and intervention
- Increased awareness of impact on patient quality of life
- Patient and care-partner support
- FDA-approved therapies
References:
- Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. Kidney Int. 2021;100(4S):S1-S276.
- D’Agati VD et al. N Engl J Med. 2011;365:2398-2411.
- Mariani LH et al. Am J Kidney Dis. 2025;85(5):610-617.
- Shabaka A et al. Nephron. 2020;144(9):413-427.
- Jefferson JA et al. Adv Chronic Kidney Dis. 2014;21(5):408-416.
- Kohan DE et al. Clinical Science (Lond). 2024;138:645-662.
- Bensink ME et al. Kidney Med. 2023;6(2):100760.
- Velez JCQ et al. Kidney360. 2024;5(8):1145-1153.
- Szklarzewicz J et al. Qual Life Res. 2025;34:1925–1937.
- Mathias SD et al. Am J Kidney Dis. 2017;70:532-540.
- Trachtman H. Expert Opin Emerg Drugs. 2020;25(3):367-375.
- Goldschmidt D et al. PLOS ONE. 2024;19(12):e0315302.
- Shoji J et al. Nephron. 2020;144(1):65-70.
MA-DS-25-0084 | September 2025
