Methylglyoxal as a prognostic factor in patients with chronic kidney disease

Nephrology (Carlton). 2019 Sep;24(9):943-950. doi: 10.1111/nep.13526. Epub 2019 Apr 29.

Abstract

Aim: Advanced glycation end products and their precursors cause vascular damage through oxidative stress. We investigated the hypothesis that methylglyoxal (MG), 3-deoxyglucosone (3-DG) and pentosidine influence outcomes of chronic kidney disease (CKD) patients.

Methods: We conducted a 3 years prospective observational study involving 150 outpatients at CKD stages 3-5. At enrolment, MG, 3-DG and pentosidine plasma concentrations were measured; patients were divided into tertiles according to the concentration of each substance. The primary endpoint was death, a cardiovascular event or end-stage renal disease. Survival analysis was performed using the Cox regression model.

Results: The patients' mean age was 62 ± 12 years, 97 were men, and 20 had diabetic nephropathy. The mean estimated glomerular filtration rate was 25.0 ± 12.1 mL/min per 1.73 m2 , which negatively correlated with MG but not with 3-DG and pentosidine. Forty-eight patients reached the primary endpoint. Compared with the lowest MG tertile, the hazard ratio for the primary endpoint was 7.57 (95% confidence interval (CI): 1.71-33.54) in the middle tertile and 27.00 (CI: 6.46-112.82) in the highest tertile. When adjusted for characteristics at baseline, the corresponding hazard ratio decreased to 2.09 (CI: 0.37-11.96) and 6.13 (CI: 0.97-38.82), but MG tertile remained an independent risk factor for the primary endpoint. However, 3-DG and pentosidine were not related to the primary outcome.

Conclusion: Methylglyoxal has a close clinical association with CKD. Higher MG concentrations may contribute renal function deterioration in CKD. In CKD patients, MG concentration might be useful when determining the prognosis.

Keywords: advanced glycation end products; cardiovascular disease; chronic kidney disease; end-stage kidney disease.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Aged
  • Arginine / analogs & derivatives
  • Arginine / blood
  • Biomarkers / blood
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / mortality
  • Deoxyglucose / analogs & derivatives
  • Deoxyglucose / blood
  • Diabetic Nephropathies / blood*
  • Diabetic Nephropathies / diagnosis
  • Diabetic Nephropathies / mortality
  • Disease Progression
  • Female
  • Humans
  • Japan
  • Kidney Failure, Chronic / blood*
  • Kidney Failure, Chronic / diagnosis
  • Kidney Failure, Chronic / mortality
  • Lysine / analogs & derivatives
  • Lysine / blood
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prospective Studies
  • Pyruvaldehyde / blood*
  • Renal Insufficiency, Chronic / blood*
  • Renal Insufficiency, Chronic / diagnosis
  • Renal Insufficiency, Chronic / mortality
  • Risk Factors
  • Time Factors
  • Up-Regulation

Substances

  • Biomarkers
  • 3-deoxyglucose
  • Pyruvaldehyde
  • Arginine
  • Deoxyglucose
  • pentosidine
  • Lysine

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