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Abstract: SA-PO349

Carbamylated Homocitrulline Is Associated with Left Ventricular Hypertrophy in CKD: Results from the CAIN Study

Session Information

Category: Hypertension and CVD

  • 1403 Hypertension and CVD: Mechanisms

Authors

  • Lu, Tzongshi, Brigham and Women's Hospital, Harvard Medical School, Natick, Massachusetts, United States
  • Lim, Kenneth, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
  • Song, Michelle D., Brigham and Women's Hospital, Harvard Medical School, Natick, Massachusetts, United States
  • Liu, Jialing, Brigham and Women's Hospital, Harvard Medical School, Natick, Massachusetts, United States
  • Siedlecki, Andrew M., Brigham and Women's Hospital, Harvard Medical School, Natick, Massachusetts, United States
  • Thadhani, Ravi I., Cedars-Sinai, Los Angeles, California, United States
  • Kalim, Sahir, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
Background

Carbamylated proteins arise from post-translational modifications that accelerate with renal failure, can cause molecular and cellular dysfunction, and have been strongly associated to the presence of cardiovascular disease among patients with chronic kidney disease (CKD). To-date, it is unknown whether tissue levels of carbamylated proteins are linked to specific cardiac outcomes such as left ventricular hypertrophy (LVH). We hypothesized that carbamylated protein burden in cardiac tissue is associated with LVH in dialysis patients.

Methods

We analyzed 47 left ventricular (LV) human heart tissues collected in The CAIN (Cardiac Aging in CKD) Study Cohort. LV tissues from hemodialysis (HD; n=17), hypertensive (HTN; n=10) and healthy controls (n=20) were analyzed in a 3-arm cross-sectional controlled design. All tissues underwent gross pathologic exam. Tissue carbamylation levels was assessed by western blotting using an antibody specific to homocitrulline as a marker (Cat. No. 22428, Cayman Chemical, MI, USA). Multiple regression analysis was performed to determine the association between carbamylated tissue levels and left ventricular free wall thickness (LVWT), an index of LVH.

Results

Across all 3 groups, there was no statistical difference in age (HD 46.2±11.2; HTN 55.9±5.0; control 49.2±15.3 yrs, p=0.2), gender (HD 59; HTN 60; control 50 % male, p=0.9) or BMI (HD 27.0±4.8; HTN 30.9±6.6; control 26.5±5.9 kg/m2, p=0.1). HTN and HD patients had significantly greater LVWT standardized by body surface area on gross pathologic exam (p<0.0001). Basal homocitrulline was detected in LV tissues from control donors, however LV tissues from HTN patients exhibited increased homocitrulline levels (1.6-fold), while HD patients had even greater levels (2.3-fold) compared to control (P<0.0001). Multiple adjusted regression analysis showed that carbamylated homocitrulline levels was significantly associated with LVWT (p<0.05).

Conclusion

This present study is the first to assess carbamylated tissue levels in human hearts. We provide evidence that homocitrulline in LV tissues is associated with LVH as assessed by LVWT. Further studies are critically needed to determine the mechanisms involved.