Kidney Week

Abstract: FR-OR53

Identification of Glomerular and Plasma APOM as Novel Biomarkers in Glomerular Disease

Session Information

• Glomerular Diseases: From Bench to Bedside
  November 04, 2022 | Location: W414, Orange County Convention Center‚ West Building
  Abstract Time: 04:48 PM - 04:57 PM

Category: Glomerular Diseases

• 1303 Glomerular Diseases: Clinical‚ Outcomes‚ and Trials

Authors

• Drexler, Yelena, University of Miami School of Medicine, Miami, Florida, United States

Yelena Drexler, MD

• Kurano, Makoto, Tokyo Daigaku Daigakuin Igakukei Kenkyuka Igakubu Seirigaku, Bunkyo-ku, Tokyo, Japan

Makoto Kurano,

• Molina David, Judith T., University of Miami School of Medicine, Miami, Florida, United States

Judith T. Molina David,

• Elfassy, Tali, University of Miami School of Medicine, Miami, Florida, United States

Tali Elfassy,

• Ma, Ruixuan, University of Miami School of Medicine, Miami, Florida, United States

Ruixuan Ma,

• Christoffersen, Christina, Rigshospitalet, Kobenhavn, Denmark

Christina Christoffersen,

• Yatomi, Yutaka, Tokyo Daigaku Daigakuin Igakukei Kenkyuka Igakubu Seirigaku, Bunkyo-ku, Tokyo, Japan

Yutaka Yatomi,

• Mariani, Laura H., University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Laura H. Mariani,

• Contreras, Gabriel, University of Miami School of Medicine, Miami, Florida, United States

Gabriel Contreras,

• Merscher, Sandra M., University of Miami School of Medicine, Miami, Florida, United States

Sandra M. Merscher,

• Fornoni, Alessia, University of Miami School of Medicine, Miami, Florida, United States

Alessia Fornoni,

Background

Lipid-induced kidney injury is a highly relevant pathway in experimental models of glomerular disease (GD). Apolipoprotein M (APOM) has a crucial role in the mobilization of cellular cholesterol and modulation of the bioactive sphingolipid sphingosine-1-phosphate (S1P). APOM expression is decreased in glomeruli of patients with focal segmental glomerulosclerosis. We hypothesized that GD represents a state of glomerular APOM deficiency and that altered APOM expression and plasma APOM correlate with clinical outcomes.

Methods

GD patients from the NEPTUNE study with proteinuria >1 g/g and available microarray gene expression data were included in the analysis (n=84). Glomerular mRNA expression levels of APOM, sphingosine kinase 1 (SPHK1), and S1P receptors 1-5 (S1P1-5) were obtained from microdissected kidney tissue in GD patients and living kidney donor controls (n=6). From baseline samples, plasma APOM (pAPOM) was measured by ELISA and log₂-transformed. Plasma S1P (pS1P) and other bioactive lipids were measured by LC-MS/MS. We used Welch’s t-test to compare gene expression in GD and controls. We used correlation analyses to determine associations between glomerular APOM expression with pAPOM levels. We used linear regression to determine whether glomerular APOM, pAPOM, pS1P, and bioactive lipids were associated with baseline eGFR. Using Cox models, we determined whether glomerular APOM and pAPOM were associated with time to complete remission (CR).

Results

In GD patients compared to controls, APOM expression was reduced (P<0.01) and SPHK1 and S1P1-5 expression was increased (P<0.05), suggesting modulation of APOM/S1P signaling. APOM expression was positively correlated with pAPOM levels (R² = 0.12, P<0.01). Every unit decrease in APOM expression and pAPOM was associated with a 10.17 (95% CI, 4.35–16.00) and 14.95 (95% CI, 5.29–24.61) lower eGFR, respectively (P<0.01). pS1P was not associated with eGFR. From Cox models adjusted for age, sex, and race, pAPOM was a significant predictor of CR (HR 1.85; 95% CI, 1.06–3.23).

Conclusion

Plasma APOM is a non-invasive biomarker of glomerular APOM deficiency and is strongly associated with clinical outcomes in GD. We also found evidence supporting APOM/S1P pathway modulation, warranting further study.

Funding

• Other NIH Support