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Abstract: TH-PO244

Proteomics of Myocardial Fibrosis in Advanced CKD

Session Information

Category: Hypertension and CVD

  • 1602 Hypertension and CVD: Clinical

Authors

  • Liu, Chenyu, Case Western Reserve University, Cleveland, Ohio, United States
  • Zhang, Liangliang, Case Western Reserve University, Cleveland, Ohio, United States
  • Janus, Scott E., University Hospitals, Cleveland, Ohio, United States
  • Gaivin, Robert J., Case Western Reserve University, Cleveland, Ohio, United States
  • Iyengar, Sudha K., Case Western Reserve University, Cleveland, Ohio, United States
  • Padiyar, Aparna, University Hospitals, Cleveland, Ohio, United States
  • Rahman, Mahboob, Case Western Reserve University, Cleveland, Ohio, United States
  • Rajagopalan, Sanjay, Case Western Reserve University, Cleveland, Ohio, United States
  • Al-Kindi, Sadeer, University Hospitals, Cleveland, Ohio, United States
  • Huml, Anne M., Cleveland Clinic, Cleveland, Ohio, United States
  • Schelling, Jeffrey R., Case Western Reserve University, Cleveland, Ohio, United States
  • Dobre, Mirela A., Case Western Reserve University, Cleveland, Ohio, United States
Background

We used a large-scale, high-throughput DNA aptamer-based discovery proteomic platform to identify circulating biomarkers of myocardial fibrosis (MF) in advanced chronic kidney disease (CKD).

Methods

We evaluated 26 living kidney transplant (KT) recipients (age 53±16 years, 44% women, dialysis vintage 24.3±20 months) and 21 KT waitlisted participants (age 55±13 years, 38% women, dialysis vintage 23.2±17 months) who underwent proteomic profiling (SomaScan v.4.1) at study baseline. Living KT group had MF assessed by non-contrast cardiac magnetic resonance T1 maps prior to and 9 months post KT. Waitlisted group had T1 maps at baseline and 9 months follow-up. Plasma levels of 6472 proteins were related to baseline and change in T1 maps using DESeq2, adjusted linear regression, spike and slab regression, and Firth's bias-reduced logistic regression models. PathfindR and STRING-db v11.5 enrichment analyses were used to explore pathways.

Results

Among 126 proteins associated with baseline T1 maps, 43 remained significant after adjusting for clinical covariates (false discovery rate [FDR] adjusted p<0.05). Of these, 10 proteins were consistently selected across a large proportion of resampling iterations (>60%), with macrophage colony stimulating factor-1 (M-CSF1), displaying the greatest retest reproducibility (80%). Compared to waitlisted, KT recipients had a significant reduction in T1 maps at 9 months (79.2% vs 38.9% participants, p=0.003). Though FDR adjustment attenuated the association, greater baseline M-CSF1 was associated with decreased T1 maps in KT recipients (OR 2.53, 95%CI: 0.85, 14.11) and lower baseline M-CSF1 associated with increased T1 maps in waitlisted participants (OR 0.35, 95%CI: 0.07, 1.08). Plasma M-CSF1 levels by ELISA highly correlated with SomaScan values, and confirmed the inverse correlation with T1 maps.

Conclusion

Kidney transplantion was associated with a reduction in myocardial fibrosis measured by T1 maps. Plasma M-CSF1 was inversely associated with T1 maps and may serve as prognostic, and potentially mechanistic biomarker, conferring a protective effect against myocardal fibrosis in advanced CKD.

Funding

  • Other NIH Support