Kidney-shaped aquarium with protein streaming through cracked viewing glassKidney-shaped aquarium with protein streaming through cracked viewing glass

In Focal Segmental Glomerulosclerosis (FSGS)

Elevated Proteinuria Increases Risk of Disease Progression

Elevated proteinuria correlates with accelerated decline in kidney function and reduced survival probability in FSGS1-3

FSGS is characterized by glomerular injury resulting from podocyte damage.4

Reduction of proteinuria to remission and partial remission thresholds can significantly improve outcomes.1,5-7

TARGET PROTEINURIA GOAL6,7,a

<1.5 g/g

Achieving this goal correlates with extended kidney survival

aFSGS partial remission threshold defined as <1.5 g/g with a 40% reduction from baseline.

Significantly extended survival in patients with FSGS who achieved <1.5 g/g and 40% decrease in PCR7,b

Graph depicts survival data from Saleem 2021 study showing that achievement of complete or partial remission of proteinuria resulted in a 13-year improvement in survival probabilityGraph depicts survival data from Saleem 2021 study showing that achievement of complete or partial remission of proteinuria resulted in a 13-year improvement in survival probability

Endpoints based on PCR follow-up 6 to 12 months from first nephrotic-range PCR valuec:

CR/FPRE-R, PCR <1.5 g/g and 40% decrease in PCR

FPRE-NR, not achieving CR/FPRE-R

Reducing proteinuria from nephrotic-range baseline to <1.5 g/g correlated with a 13-year extension in median survival probability vs patients who did not reach this thresholdc

CR=complete remission; eGFR=estimated glomerular filtration rate; ESKD=end-stage kidney disease; FPRE=FSGS partial remission endpoint; FPRE-NR=FPRE-non-responder; FPRE-R=FPRE-responder; FSGS=focal segmental glomerulosclerosis; PCR=protein-creatinine ratio; UP/C=urinary protein-to-creatinine ratio.

bTime to ESKD or death was analyzed using accelerated failure time modelling of the Weibull distribution and Kaplan-Meier estimates of cumulative incidence.

cBaseline pertains to first nephrotic-range proteinuria value (≥3.0 g/g) at or after disease onset.

Based on data from the National Registry of Rare Kidney Diseases (RaDaR), a UK Kidney Association initiative, in 270 patients with FSGS (150 adults age 18 and older and 120 pediatrics) with long-term data collection and comprehensive follow-up, representing a nationwide database and involving a large proportion of UK renal centers. ESKD was defined as chronic kidney disease stage 5 (confirmed eGFR <15 mL/min/1.73m2 or CKD stage 5 recorded in RaDaR) or receiving chronic dialysis or kidney transplant. Time to ESKD or death was analyzed using accelerated failure time modeling.

Epidemiology of FSGS

  • FSGS is a leading glomerular cause of kidney failure.8
  • Affects those of all ages and represents a significant proportion of glomerulopathy diagnoses.9,d
  • Is prevalent in patients with recent African ancestry, with up to 80% of biopsies identifying FSGS as the cause of idiopathic nephrotic syndrome.10,e
  • In adults, identifying FSGS requires biopsy. Further evaluation may be required to differentiate the classification of primary, genetic, or secondary FSGS, or FSGS of undetermined cause (FSGS-UC).5

dAnalyses conducted from the NEPTUNE cohort; n=441 proteinuric patients (≥0.5 g/24 hrs) undergoing kidney biopsy; NEPTUNE=Nephrotic Syndrome Study Network.

eBased on US data.

Endothelin-1 and angiotensin II are key mechanisms of disease progression in FSGS11:

  • Work in tandem to amplify podocyte injury
  • Causing injury resulting in glomerular filtration breakdown
  • Increasing proteinuria

Treatment options are limited

There are no FDA-approved drugs indicated for the treatment of FSGS.12

Treatment strategies are based on limited evidence and include5,12:

  • Immunosuppressive treatment
  • ACEi/ARB

Research is ongoing to help address the needs in patients with FSGS who are at high risk of rapid progression13

Endothelin-1 and angiotensin II work in tandem to exacerbate kidney injury

ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin II receptor blocker; FDA=Food and Drug Administration; IgA=immunoglobulin A.

References:

1. Troyanov S, et al. J Am Soc Nephrol. 2005;16:1061-1068. 2. Le WB, et al. Nephrol Dial Transplant. 2012;27:1479-1485. 3. Reich HN, et al. J Am Soc Nephrol. 2007;18:3177-3183. 4. D’Agati VD, et al. New Engl J Med. 2011;365:2398-2411. 5. Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. Kidney Int. 2021;100(4S):S1-S276. 6. Troost JP, et al. Clin J Am Soc Nephrol. 2018;13:414-421. 7. Saleem MA, et al. American Society of Nephrology (ASN) Kidney Week virtual, November 4-7, 2021. PO1529. 8. Rosenberg AZ, Kopp JB. Clin J Am Soc Nephrol. 2017;12:502-517. 9. Gipson DS, et al. Clin J Am Soc Nephrol. 2016;11:81-89. 10. Korbet SM. J Am Soc Nephrol. 2012;23:1769-1776. 11. Komers R, et al. Am J Physiol Regul Integr Comp Physiol. 2016:R877-R884. 12. Raina R, et al. Kidney Dis. 2020;6:22-34. 13. 13. Nephcure Kidney International. Accessed June 23, 2022. https://kidneyhealthgateway.com/trials-research/.

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