The Association of dp-ucMGP with Cardiovascular Morbidity and Decreased Renal Function in Diabetic Chronic Kidney Disease

Int J Mol Sci. 2020 Aug 21;21(17):6035. doi: 10.3390/ijms21176035.

Abstract

We aimed to investigate the possible association of the inactive, dephosphorylated, uncarboxylated matrix Gla protein (dp-ucMGP) with oxidized low-density lipoprotein (ox-LDL) and all-cause/cardiovascular (CV) mortality and renal function in diabetic chronic kidney disease (CKD). Ox-LDL and dp-ucMGP were determined in 66 diabetic CKD patients. All patients were prospectively followed for seven years, or until the occurrence of death, or a composite renal outcome of 30% estimated glomerular filtration rate (eGFR) reduction or progression to end-stage renal disease (ESRD) requiring dialysis occurred. Secondary outcomes were the occurrence of CV events. Kaplan-Meier curves showed that patients with plasma dp-ucMGP levels above the median (≥656 pM) had a significantly higher risk for all study endpoints. After adjustment for several well-known cofounders, multivariate Cox analysis showed that high plasma dp-ucMGP levels were associated with all-cause mortality (Hazard ratio-HR = 2.63, 95% Confidence Interval-CI = 1.17-5.94, p = 0.02), CV mortality (HR = 2.82, 95% CI = 1.07-7.49, p = 0.037) and progression of CKD (HR = 4.02, 95% CI = 1.20-13.46, p = 0.024). Circulating dp-ucMGP is associated with mortality and decreased renal function in diabetic CKD.

Keywords: cardiovascular disease; chronic kidney disease; dephosphorylated uncarboxylated matrix Gla protein; diabetic kidney disease.

MeSH terms

  • Aged
  • Biomarkers / blood
  • Calcium-Binding Proteins / blood*
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / mortality
  • Cardiovascular Diseases / therapy
  • Chronic Disease
  • Diabetic Nephropathies / blood*
  • Diabetic Nephropathies / diagnosis
  • Diabetic Nephropathies / mortality
  • Diabetic Nephropathies / therapy
  • Disease Progression
  • Extracellular Matrix Proteins / blood*
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Kidney Failure, Chronic / blood*
  • Kidney Failure, Chronic / diagnosis
  • Kidney Failure, Chronic / mortality
  • Kidney Failure, Chronic / therapy
  • Lipoproteins, LDL / blood
  • Male
  • Matrix Gla Protein
  • Middle Aged
  • Prospective Studies
  • Renal Dialysis
  • Survival Analysis

Substances

  • Biomarkers
  • Calcium-Binding Proteins
  • Extracellular Matrix Proteins
  • Lipoproteins, LDL
  • oxidized low density lipoprotein