Urinary peptidomic biomarkers of renal function in heart transplant recipients

Nephrol Dial Transplant. 2019 Aug 1;34(8):1336-1343. doi: 10.1093/ndt/gfy185.

Abstract

Background: Chronic kidney disease (CKD) is common in patients after heart transplantation (HTx). We assessed whether in HTx recipients the proteomic urinary classifier CKD273 or sequenced urinary peptides revealing the parental proteins correlated with the estimated glomerular filtration rate (eGFR).

Methods: In 368 HTx patients, we measured the urinary peptidome and analysed CKD273 and 48 urinary peptides with a detectable signal in >95% of participants. After 9.1 months (median), eGFR and the urinary biomarkers were reassessed.

Results: In multivariable Bonferroni-corrected analyses of the baseline data, a 1-SD increase in CKD273 was associated with a 11.4 [95% confidence interval (CI) 7.25-15.5] mL/min/1.73 m2 lower eGFR and an odds ratio of 2.63 (1.56-4.46) for having eGFR <60 mL/min/1.73 m2. While relating eGFR category at follow-up to baseline urinary biomarkers, CKD273 had higher (P = 0.007) area under the curve (0.75; 95% CI 0.70-0.80) than 24-h proteinuria (0.64; 95% CI 0.58-0.69), but additional adjustment for baseline eGFR removed significance of both biomarkers. In partial least squares analysis, the strongest correlates of the multivariable-adjusted baseline eGFR were fragments of collagen I (positive) and the mucin-1 subunit α (inverse). Associations between the changes in eGFR and the urinary markers were inverse for CKD273 and mucin-1 and positive for urinary collagen I.

Conclusions: With the exception of baseline eGFR, CKD273 was more closer associated with imminent renal dysfunction than 24-h proteinuria. Fragments of collagen I and mucin-1-respectively, positively and inversely associated with eGFR and change in eGFR-are single-peptide markers associated with renal dysfunction.

Keywords: collagen; glomerular filtration; heart transplantation; mucin-1; urinary proteomics.

MeSH terms

  • Adult
  • Aged
  • Biomarkers / urine
  • Collagen Type I / urine
  • Female
  • Glomerular Filtration Rate
  • Heart Diseases / complications*
  • Heart Diseases / surgery*
  • Heart Diseases / urine
  • Heart Transplantation / adverse effects*
  • Humans
  • Kidney Function Tests
  • Least-Squares Analysis
  • Male
  • Middle Aged
  • Mucin-1 / urine
  • Multivariate Analysis
  • Peptides / urine*
  • Proteomics
  • Renal Insufficiency, Chronic / complications*
  • Renal Insufficiency, Chronic / etiology
  • Renal Insufficiency, Chronic / urine
  • Sensitivity and Specificity

Substances

  • Biomarkers
  • Collagen Type I
  • Mucin-1
  • Peptides