Circulating metabolic biomarkers of renal function in diabetic and non-diabetic populations

Clara Barrios, Jonas Zierer, Peter Würtz, Toomas Haller, Andres Metspalu, Christian Gieger, Barbara Thorand, Christa Meisinger, Melanie Waldenberger, Olli Raitakari, Terho Lehtimäki, Sol Otero, Eva Rodríguez, Juan Pedro-Botet, Mika Kähönen, Mika Ala-Korpela, Gabi Kastenmüller, Tim D Spector, Julio Pascual, Cristina Menni

Research output: Contribution to journalArticle (Academic Journal)peer-review

13 Citations (Scopus)


Using targeted NMR spectroscopy of 227 fasting serum metabolic traits, we searched for novel metabolic signatures of renal function in 926 type 2 diabetics (T2D) and 4838 non-diabetic individuals from four independent cohorts. We furthermore investigated longitudinal changes of metabolic measures and renal function and associations with other T2D microvascular complications. 142 traits correlated with glomerular filtration rate (eGFR) after adjusting for confounders and multiple testing: 59 in diabetics, 109 in non-diabetics with 26 overlapping. The amino acids glycine and phenylalanine and the energy metabolites citrate and glycerol were negatively associated with eGFR in all the cohorts, while alanine, valine and pyruvate depicted opposite association in diabetics (positive) and non-diabetics (negative). Moreover, in all cohorts, the triglyceride content of different lipoprotein subclasses showed a negative association with eGFR, while cholesterol, cholesterol esters (CE), and phospholipids in HDL were associated with better renal function. In contrast, phospholipids and CEs in LDL showed positive associations with eGFR only in T2D, while phospholipid content in HDL was positively associated with eGFR both cross-sectionally and longitudinally only in non-diabetics. In conclusion, we provide a wide list of kidney function-associated metabolic traits and identified novel metabolic differences between diabetic and non-diabetic kidney disease.

Original languageEnglish
Pages (from-to)15249
JournalScientific Reports
Issue number1
Publication statusPublished - 15 Oct 2018

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