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Updated: May 12, 2025

Assessment of Vascular Function in Patients With Chronic Kidney Disease
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Cardiometabolic protein expression levels and pathways associated with kidney function decline in older European

Ryan E Aylward1,2, Samantha Hayward3,4, Nicholas C Chesnaye5,6

  • 1Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.

Clinical Kidney Journal
|May 9, 2025
PubMed

Insights

This study links higher levels of specific proteins, including Receptor-type tyrosine-protein phosphatase S, to faster kidney function decline in older adults with advanced chronic kidney disease (CKD). These findings highlight fibrogenesis and complement pathways in CKD progression.

Area of Science:

  • Proteomics
  • Nephrology
  • Cardiovascular Medicine

Background:

  • Cardiovascular disease (CVD) and chronic kidney disease (CKD) share similar pathophysiological mechanisms.
  • Investigating protein expression in advanced CKD can elucidate kidney function decline.
  • Older adults with advanced CKD present a critical population for understanding disease progression.

Purpose of the Study:

  • To investigate the associations between cardiometabolic protein expression and pathways with kidney function decline.
  • To explore the mechanisms underlying CKD progression in older adults.
  • To identify specific proteins and pathways linked to the rate of estimated glomerular filtration rate (eGFR) decline.

Main Methods:

  • Utilized plasma proteomic panels (Olink cardiometabolic T96 and cardiovascular II T96) from the European Quality (EQUAL) Study.
  • Analyzed longitudinal estimated glomerular filtration rate (eGFR) data from European adults aged over 65 with advanced CKD (eGFR <20 mL/min/1.73 m²).
  • Employed generalized linear mixed-effects models to estimate protein-slope associations and pathway enrichment analysis for biological pathways.

Main Results:

  • Higher expression of Receptor-type tyrosine-protein phosphatase S, Insulin-like growth factor binding protein 6, and Ficolin 2 were significantly associated with accelerated eGFR decline.
  • A doubling of Receptor-type tyrosine-protein phosphatase S expression correlated with a -15.4% annual change in eGFR.
  • Validated associations were found between specific proteins and the rate of kidney function loss across discovery and validation cohorts.

Conclusions:

  • Elevated protein expression and pathways related to fibrogenesis and the complement cascade are associated with kidney function loss in advanced CKD.
  • These findings suggest potential therapeutic targets for slowing CKD progression.
  • Further research is needed to validate these findings and explore kidney cellular proteomic signatures.
Abstract

Keywords:
chronic kidney diseasefibrosisprogressionproteins

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