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Proteomics of CKD progression in the chronic renal insufficiency cohort

Ruth F Dubin1, Rajat Deo2, Yue Ren3

  • 1Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, TX, USA. ruth.dubin@utsouthwestern.edu.

Nature Communications
|October 10, 2023
PubMed

Insights

Researchers identified 100 plasma proteins linked to chronic kidney disease (CKD) progression. A 65-protein model predicts risk, offering potential therapeutic targets to slow kidney failure.

Area of Science:

  • Nephrology
  • Proteomics
  • Biomarker Discovery

Background:

  • Chronic kidney disease (CKD) progression leads to severe complications, including kidney failure.
  • Identifying predictive biomarkers is crucial for managing CKD and preventing adverse outcomes.

Purpose of the Study:

  • To identify circulating proteins associated with CKD progression.
  • To develop a predictive risk model for kidney failure.
  • To explore potential therapeutic targets for slowing CKD.

Main Methods:

  • Analysis of 4638 plasma proteins in 3235 participants from the Chronic Renal Insufficiency Cohort Study over 10 years.
  • Primary outcome: 50% decline in estimated glomerular filtration rate or kidney failure.
  • Validation in the Atherosclerosis Risk in the Communities study; Bonferroni correction for statistical significance.

Main Results:

  • 100 circulating proteins associated with CKD progression identified.
  • Biological pathways implicated include bone morphogenetic proteins, ephrin signaling, and prothrombin activation.
  • A 65-protein risk model demonstrated excellent discrimination (C-statistic: 0.862).
  • Five potentially causal proteins identified via Mendelian randomization: EGFL9, LRP-11, MXRA7, IL-1 sRII, and ILT-2.
  • 14 of the 65 proteins in the risk model are druggable targets.

Conclusions:

  • Circulating proteins are significantly associated with CKD progression and kidney failure.
  • A multi-protein risk model shows high predictive accuracy.
  • Identified proteins and pathways offer novel therapeutic targets for slowing CKD progression.

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