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Kidney Week

Abstract: FR-PO355

Follistatin-Like Protein 1 (FSTL1) Expression Is Correlated with Measures of Kidney Injury in the Nephrotic Syndrome Study Network (NEPTUNE) Cohort

Session Information

  • CKD: Mechanisms - II
    November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Maksimowski, Nicholas, University of Toronto, Toronto, Ontario, Canada
  • Pei, York P., University Health Network and University of Toronto, Toronto, Ontario, Canada
  • Reich, Heather N., Toronto General Hospital, Toronto, Ontario, Canada
  • Scholey, James W., University of Toronto, Toronto, Ontario, Canada
Background

The pathogenesis of progressive kidney injury has not been fully elucidated in chronic kidney disease (CKD). Gene expression profiling of renal cortical mRNA samples was performed in male Col4a3-/- and Col4a3+/+ mice at 4 and 7 weeks of age. Our microarray analysis showed that FSTL1 was one of only three genes upregulated at 4-weeks of age. FSTL1 is expressed in interstitial fibroblasts. It activates NFkB and increases COL1α1 expression in proximal tubule cells. There is limited data on FSTL1 in human CKD.

Methods

The NEPTUNE cohort was used to relate clinical variables to candidate gene expression to FSTL1 mRNA levels in the tubulointerstitial compartment of the kidney. Our study focused on patients with nephrotic syndrome due to primary focal segmental glomerulosclerosis (FSGS), immunoglobulin A nephropathy (IgAN), and membranous nephropathy (MN).

Results

Analysis revealed FSTL1 was inversely correlated with eGFR in the FSGS (r=-0.4473, p=<0.0001), IgAN (r=-0.6751, p=0.0011), and MN cohorts (r=-0.4122, p=0.0101). Additionally, FSTL1 correlated with proteinuria in FSGS (r=0.3368, p=0.0007) and IgAN (r=0.4352, p=0.0162) but less so in MN (r=0.2665, p=0.0515). In terms of histopathology FSTL1 was also related to interstitial fibrosis in FSGS (r=0.4477, p=<0.0001), IgAN (r=0.751, p=0.0001), and MN (r=0.5445, p=0.0004). FSTL1 was also related to tubular atrophy in FSGS (r=0.4465, p=<0.0001), IgAN (r=0.7523, p=0.0001), and MN (r=0.5246, p=0.0007). Finally, FSTL1 mRNA levels were also positively correlated with injury makers NGAL and KIM-1, extracellular matrix protein genes, cytokine gene expression (COL1α1 and TGFβ1), and genes involved in inflammation (CCL2 and TNF-α) in all three cohorts (p=<0.0026).

Conclusion

FSTL1 was inversely correlated with eGFR and positively correlated with interstitial fibrosis and tubular atrophy in all three of the cohorts. FSTL1 mRNA levels also correlated with injury markers and extracellular matrix protein gene expression. These findings support the hypothesis that FSTL1 may be a novel determinant of progressive CKD in primary nephrotic syndrome.