Identification of Glomerular and Plasma Apolipoprotein M as Novel Biomarkers in Glomerular Disease
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Identification of Glomerular and Plasma Apolipoprotein M as Novel Biomarkers in Glomerular Disease. / Drexler, Yelena; Molina, Judith; Elfassy, Tali; Ma, Ruixuan; Christoffersen, Christina; Kurano, Makoto; Yatomi, Yutaka; Mariani, Laura H.; Contreras, Gabriel; Merscher, Sandra; Fornoni, Alessia.
I: Kidney International Reports, Bind 8, Nr. 4, 2023, s. 884-897.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Identification of Glomerular and Plasma Apolipoprotein M as Novel Biomarkers in Glomerular Disease
AU - Drexler, Yelena
AU - Molina, Judith
AU - Elfassy, Tali
AU - Ma, Ruixuan
AU - Christoffersen, Christina
AU - Kurano, Makoto
AU - Yatomi, Yutaka
AU - Mariani, Laura H.
AU - Contreras, Gabriel
AU - Merscher, Sandra
AU - Fornoni, Alessia
N1 - Publisher Copyright: © 2023 International Society of Nephrology
PY - 2023
Y1 - 2023
N2 - Introduction: Dysregulation of sphingolipid and cholesterol metabolism contributes to the pathogenesis of glomerular diseases (GDs). Apolipoprotein M (ApoM) promotes cholesterol efflux and modulates the bioactive sphingolipid sphingosine-1-phosphate (S1P). Glomerular ApoM expression is decreased in patients with focal segmental glomerulosclerosis (FSGS). We hypothesized that glomerular ApoM deficiency occurs in GD and that ApoM expression and plasma ApoM correlate with outcomes. Methods: Patients with GD from the Nephrotic Syndrome Study Network (NEPTUNE) were studied. We compared glomerular mRNA expression of ApoM (gApoM), sphingosine kinase 1 (SPHK1), and S1P receptors 1 to 5 (S1PR1–5) in patients (n = 84) and controls (n = 6). We used correlation analyses to determine associations between gApoM, baseline plasma ApoM (pApoM), and urine ApoM (uApoM/Cr). We used linear regression to determine whether gApoM, pApoM, and uApoM/Cr were associated with baseline estimated glomerular filtration rate (eGFR) and proteinuria. Using Cox models, we determined whether gApoM, pApoM, and uApoM/Cr were associated with complete remission (CR) and the composite of end-stage kidney disease (ESKD) or ≥40% eGFR decline. Results: gApoM was reduced (P < 0.01) and SPHK1 and S1PR1 to 5 expression was increased (P < 0.05) in patients versus controls, consistent with ApoM/S1P pathway modulation. gApoM positively correlated with pApoM in the overall cohort (r = 0.34, P < 0.01) and in the FSGS (r = 0.48, P < 0.05) and minimal change disease (MCD) (r = 0.75, P < 0.05) subgroups. Every unit decrease in gApoM and pApoM (log2) was associated with a 9.77 ml/min per 1.73 m2 (95% confidence interval [CI]: 3.96−15.57) and 13.26 ml/min per 1.73 m2 (95% CI: 3.57−22.96) lower baseline eGFR, respectively (P < 0.01). From Cox models adjusted for age, sex, or race, pApoM was a significant predictor of CR (hazard ratio [HR]: 1.85; 95% CI: 1.06–3.23). Conclusions: pApoM is a potential noninvasive biomarker of gApoM deficiency and strongly associates with clinical outcomes in GD.
AB - Introduction: Dysregulation of sphingolipid and cholesterol metabolism contributes to the pathogenesis of glomerular diseases (GDs). Apolipoprotein M (ApoM) promotes cholesterol efflux and modulates the bioactive sphingolipid sphingosine-1-phosphate (S1P). Glomerular ApoM expression is decreased in patients with focal segmental glomerulosclerosis (FSGS). We hypothesized that glomerular ApoM deficiency occurs in GD and that ApoM expression and plasma ApoM correlate with outcomes. Methods: Patients with GD from the Nephrotic Syndrome Study Network (NEPTUNE) were studied. We compared glomerular mRNA expression of ApoM (gApoM), sphingosine kinase 1 (SPHK1), and S1P receptors 1 to 5 (S1PR1–5) in patients (n = 84) and controls (n = 6). We used correlation analyses to determine associations between gApoM, baseline plasma ApoM (pApoM), and urine ApoM (uApoM/Cr). We used linear regression to determine whether gApoM, pApoM, and uApoM/Cr were associated with baseline estimated glomerular filtration rate (eGFR) and proteinuria. Using Cox models, we determined whether gApoM, pApoM, and uApoM/Cr were associated with complete remission (CR) and the composite of end-stage kidney disease (ESKD) or ≥40% eGFR decline. Results: gApoM was reduced (P < 0.01) and SPHK1 and S1PR1 to 5 expression was increased (P < 0.05) in patients versus controls, consistent with ApoM/S1P pathway modulation. gApoM positively correlated with pApoM in the overall cohort (r = 0.34, P < 0.01) and in the FSGS (r = 0.48, P < 0.05) and minimal change disease (MCD) (r = 0.75, P < 0.05) subgroups. Every unit decrease in gApoM and pApoM (log2) was associated with a 9.77 ml/min per 1.73 m2 (95% confidence interval [CI]: 3.96−15.57) and 13.26 ml/min per 1.73 m2 (95% CI: 3.57−22.96) lower baseline eGFR, respectively (P < 0.01). From Cox models adjusted for age, sex, or race, pApoM was a significant predictor of CR (hazard ratio [HR]: 1.85; 95% CI: 1.06–3.23). Conclusions: pApoM is a potential noninvasive biomarker of gApoM deficiency and strongly associates with clinical outcomes in GD.
KW - apolipoprotein M
KW - biomarkers
KW - glomerular disease
KW - nephrotic syndrome
KW - outcome prediction
UR - http://www.scopus.com/inward/record.url?scp=85150075319&partnerID=8YFLogxK
U2 - 10.1016/j.ekir.2023.01.031
DO - 10.1016/j.ekir.2023.01.031
M3 - Journal article
C2 - 37069998
AN - SCOPUS:85150075319
VL - 8
SP - 884
EP - 897
JO - Kidney International Reports
JF - Kidney International Reports
SN - 2468-0249
IS - 4
ER -
ID: 340406591