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Abstract: TH-PO0620

Proteomic Signatures of Early Albuminuria: Evidence from MESA and CARDIA

Session Information

Category: CKD (Non-Dialysis)

  • 2202 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

  • Vivek, Sithara, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Wang, Jianfeng, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Rotter, Jerome I., The Lundquist Institute, Torrance, California, United States
  • Thyagarajan, Bharat, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Guan, Weihua, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Deo, Rajat, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Rich, Stephen, University of Virginia, Charlottesville, Virginia, United States
  • Dubin, Ruth F., The University of Texas Southwestern Medical Center, Dallas, Texas, United States
  • Kramer, Holly J., Loyola University Chicago, Chicago, Illinois, United States
  • Franceschini, Nora, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  • Shlipak, Michael G., University of California San Francisco, San Francisco, California, United States
  • Ganz, Peter, University of California San Francisco, San Francisco, California, United States
  • Jacobs, David R., University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Tang, Weihong, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
Background

Albuminuria (urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g) is an early marker of kidney and vascular injury, but its proteomic correlates in community-based populations are poorly characterized. We examined circulating proteins associated with prevalent and incident albuminuria in MESA and evaluated replication in CARDIA. Both cohorts were free of cardiovascular disease, had eGFR ≥ 60 and were followed for ~10 years.

Methods

Plasma proteins were measured using SomaScan v4.1 (~7,000 aptamers; 5,731 proteins after QC). In MESA, associations with ln(UACR), prevalent albuminuria, longitudinal ln(UACR) change, and incident albuminuria were evaluated using linear, logistic, mixed effects, and Cox models, respectively. Models adjusted for demographics, smoking, BMI, eGFR, and cardiovascular risk factors with FDR control. Significant proteins from MESA (Exam 1, 2000) were tested in CARDIA (Year 25, 2010) using analogous models with ~10 years of follow-up.

Results

MESA (n=4,862) participants were older (60.9 vs 50.2 years) with higher albuminuria prevalence (7.7% vs 5.6%) than CARDIA (n=2,615). In MESA, several proteins were associated with ln(UACR) (n=1,119), prevalent albuminuria (n=277), longitudinal ln(UACR) change (n=421), and incident albuminuria (n=228), with consistent patterns across analyses after covariate adjustment (Figure 1). In CARDIA, 177 proteins were replicated for ln(UACR), 25 for prevalent albuminuria, and 42 for longitudinal change; three showed nominal significance for incident albuminuria (FDR p≈0.07), supporting generalizability in a younger, lower-risk cohort. Replicated proteins reflected pathways of tubular injury and vascular remodeling.

Conclusion

Proteomic signatures of albuminuria were identified in MESA and replicated in CARDIA, highlighting pathways of tubular injury, and vascular dysfunction in individuals with preserved eGFR.

Figure 1