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Abstract: PO1977

Apolipoprotein M as a Biomarker of Glomerular Lipotoxicity in Nephrotic Syndrome

Session Information

  • Podocyte Biology
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

  • 1204 Podocyte Biology

Authors

  • Drexler, Yelena R., University of Miami Katz Family Division of Nephrology and Hypertension, Miami, Florida, United States
  • Molina David, Judith T., University of Miami Katz Family Division of Nephrology and Hypertension, Miami, Florida, United States
  • Merscher, Sandra M., University of Miami Katz Family Division of Nephrology and Hypertension, Miami, Florida, United States
  • Fornoni, Alessia, University of Miami Katz Family Division of Nephrology and Hypertension, Miami, Florida, United States
Background

Dysregulation of intrarenal metabolic pathways involved in cholesterol efflux is implicated in lipid-induced podocyte injury in glomerular diseases. Among several genes that are involved in cholesterol efflux, we recently reported a significant downregulation of glomerular apolipoprotein M (APOM) expression in patients with FSGS. HDL-associated APOM facilitates reverse cholesterol transport and is the carrier for the bioactive sphingolipid sphingosine-1-phosphate (S1P). Mutations in S1P lyase, the enzyme responsible for S1P degradation, cause a familial form of FSGS. We hypothesize that glomerular APOM deficiency is a surrogate biomarker for lipid-induced kidney injury in NS.

Methods

Patients with FSGS, MN, and MCD enrolled in NEPTUNE, a multi-center observational cohort study of children and adults with NS, who had uPCR >1 g/g at baseline were selected for analysis. RNA expression data were obtained from the glomerular compartment isolated from kidney biopsies and compared with living kidney donor controls. Plasma and urinary APOM levels were measured by ELISA using baseline samples. Linear regression analysis was used to correlate glomerular APOM expression with plasma and urinary levels of APOM and to correlate glomerular APOM expression and plasma and urinary APOM levels with eGFR at baseline.

Results

Among 84 patients, 68% were male, mean age was 40 years, mean baseline eGFR was 80.6 mL/min/1.73m2, and mean uPCR was 4.9 g/g. Glomerular APOM expression was decreased in patients with NS compared to healthy controls (p <0.001), irrespective of histologic diagnosis. APOM expression was positively correlated with plasma but not urinary APOM levels in the NS cohort (R2 = 0.089, p = 0.003) and in the FSGS subgroup (R2 = 0.189, p = 0.0218). Decreased APOM expression (p = 0.005) and decreased plasma APOM (p = 0.031) were associated with a lower eGFR at baseline in the NS cohort. After adjustment for age, sex, and race, each unit decrease in APOM expression was associated with a 9.83 mL/min/1.73m2 (95% CI, 3.72 to 15.93, p = 0.002) lower eGFR at baseline.

Conclusion

Glomerular APOM deficiency and decreased plasma APOM levels were associated with decreased kidney function at baseline in the NS cohort. These findings identify APOM as a potential biomarker of lipid-induced kidney injury in NS.

Funding

  • NIDDK Support