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Abstract: TH-PO0345

Plasma and Urinary Oxalate Association with Circulating Proteins and Markers of Subclinical Cardiovascular Disease in the CRIC Study

Session Information

Category: Hypertension and CVD

  • 1602 Hypertension and CVD: Clinical

Authors

  • Jaber, Karim, NYU Langone Health, New York, New York, United States
  • Surapaneni, Aditya L., NYU Langone Health, New York, New York, United States
  • Cohen, Debbie L., University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States
  • Dobre, Mirela A., University Hospitals Health System, Cleveland, Ohio, United States
  • Waikar, Sushrut S., Boston Medical Center, Boston, Massachusetts, United States
  • Weir, Matthew R., University of Maryland Baltimore School of Medicine, Baltimore, Maryland, United States
  • Grams, Morgan, NYU Langone Health, New York, New York, United States
  • Nazzal, Lama, NYU Langone Health, New York, New York, United States
Background

Oxalate, a common component of the American diet, has been implicated as a potential cause of cardiovascular disease (CVD) morbidity and mortality, particularly in the dialysis population. The association of oxalate in patients with chronic kidney disease (CKD) to CVD is uncertain as oxalate excretion is impaired with progressive CKD. Leveraging the Chronic Renal Insufficiency Cohort (CRIC), we sought to evaluate the cross-sectional association of plasma (pOx) and urinary oxalate (uOx) levels with 1) untargeted circulating proteins, 2) mitral annular calcification, and 3) left ventricular mass index (LVMI) on echocardiogram.

Methods

CRIC participants with pOx (n=1535) measured by HPLC-MS metabolomics, or uOx (n=2934) measured by oxalate oxidase method scaled to 24-hour urine creatinine at the 1-year visit were included in the study. Circulating proteins were assessed by the untargeted Soma v4.1 platform; LVMI, and mitral calcification score were estimated from echocardiography. Linear regressions relating pOx and uOx and the outcomes of interest were adjusted for demographics, comorbidities, estimated glomerular filtration rate (eGFR), and CVD.

Results

The correlation between UOx and pOx was low (r=0.21). There was little association between UOx and eGFR; in contrast, pOx levels increased when eGFR <50 mL/min/1.73m2. Proteomic analysis identified 140 proteins associated with uOx and 80 with pOx after Bonferroni correction, with 33 overlapping. Several of the overlapping proteins were linked to inflammation or oxidative stress, including ceruloplasmin NADH-cytochrome b5 reductase3. Higher uOx and pOx levels were associated with higher mitral annular calcification volume (p=0.02, respectively) and higher pOx but not uOx was associated with increased LVMI (p=0.04).

Conclusion

These findings highlight potential mechanisms linking oxalate to cardiovascular risk in CKD, including inflammation, oxidative stress, valvular calcification and cardiac remodeling.

Digital Object Identifier (DOI)