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Kidney Week

Abstract: FR-PO446

Plasma Metabolomics Identifies Markers of Impaired Kidney Function: A Meta-Analysis of 1,984 Europeans with Type 2 Diabetes

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Tofte, Nete, Steno Diabetes Center Copenhagen, Copenhagen, Denmark
  • Ahluwalia, Tarunveer S., Steno Diabetes Center Copenhagen, Copenhagen, Denmark
  • Vogelzangs, Nicole, Maastricht University, Maastricht, Netherlands
  • Mook-Kanamori, Dennis O., Leiden University Medical Center, Leiden, Netherlands
  • Brahimaj, Adela, Erasmus MC, Rotterdam, Netherlands
  • Nano, Jana, Erasmuc Medical Center, Rotterdam, Netherlands
  • Willems van dijk, Ko, Leiden University Medical Center, Leiden, Netherlands
  • Frimodt-Moller, Marie, Steno Diabetes Center Copenhagen, Copenhagen, Denmark
  • Van der kallen, Carla Jh, Maastricht University, Maastricht, Netherlands
  • Arts, Ilja Cw, Maastricht University, Maastricht, Netherlands
  • Beulens, Joline, VUmc, Amsterdam, Netherlands
  • Van der heijden, Amber A., VUMC, Amsterdam, Netherlands
  • Nijpels, Giel, VU University, Amsterdam, Netherlands
  • Greevenbroek, Marleen Van, Maastricht University, Maastricht, Netherlands
  • Stehouwer, Coen, University Hospital Maastricht, Maastricht, Netherlands
  • Rossing, Peter, Steno Diabetes Center Copenhagen, Copenhagen, Denmark
  • 't Hart, Leen M., Leiden University Medical Center, Leiden, Netherlands
Background

There is a need for novel biomarkers and better understanding of the pathophysiology of diabetic kidney disease. The aim was to investigate the associations between plasma metabolites and measures of kidney function.

Methods

Blood metabolites (n=235) were measured by nuclear magnetic resonance spectroscopy (NMR) in 1,984 type 2 diabetes (T2D) cases among three independent Dutch studies (the Hoorn Diabetes Care System (DCS, n=995) cohort, the Maastricht Study (MS, n=848) and the Cohort of Diabetes and Atherosclerosis Maastricht study (CODAM, n=141)) with mean ± SD age 59.7 ± 8.8. Linear regression based associations were tested between single plasma metabolites and estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) in each study. Covariate adjustments included age, sex, systolic blood pressure, body mass index, medication (lipid-lowering, glucose-lowering, anti-hypertensive), smoking, diabetes duration, HbA1c, and eGFR or UACR, where appropriate. A fixed effect meta-analysis of the 3 study sets was performed. A Bonferroni’s correction of pbonferroni = 1.0 × 10-4 was considered significant.

Results

After adjustment for multiple testing, 82 metabolites associated significantly with eGFR while two with UACR. Alteration of several lipoprotein subclasses of VLDL and HDL as well as amino acids (phenylalanine, isoleucine and glutamine) and glycoprotein acetyls were associated with lower eGFR. Higher UACR levels were significantly associated with glycoprotein acetyls and cholesterol esters in very small VLDL.

Conclusion

The current study identifies plasma metabolites associated with decreased eGFR and albuminuria among T2D cases of European origin. These findings implicate an involvement of lipid and amino acid metabolism in the pathogenesis of DKD.

Funding

  • Government Support - Non-U.S.