Metabolites associate with kidney function decline and incident chronic kidney disease in the general population

Oemer Necmi Goek, Cornelia Prehn, Peggy Sekula, Werner Römisch-Margl, Angela Döring, Christian Gieger, Margit Heier, Wolfgang Koenig, Rui Wang-Sattler, Thomas Illig, Karsten Suhre, Jerzy Adamski, Anna Köttgen, Christa Meisinger

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Background. Serum metabolites are associated cross-sectionally with kidney function in population-based studies. Methods. Using flow injection and liquid chromatography tandem mass spectrometry methods, we examined longitudinal associations of baseline concentrations of 140 metabolites and their 19 460 ratios with kidney function decline and chronic kidney disease (CKD) incidence over 7 years in 1104 participants of the Cooperative Health Research in the Region of Augsburg S4/F4 study. Results. Corrected for multiple testing, a significant association with annual change in the estimated glomerular filtration rate was observed for spermidine (P = 5.8 × 10-7) and two metabolite ratios, the phosphatidylcholine diacyl C42:5- tophosphatidylcholine acyl-alkyl C36:0 ratio (P = 1.5 × 10-6) and the kynurenine-to-tryptophan ratio (P = 1.9 × 10-6). The kynurenine-to-tryptophan ratio was also associated with significantly higher incidence of CKD at the follow-up visit with an odds ratio of 1.36 per standard deviation increase; 95% confidence interval 1.11-1.66, P = 2.7 × 10 -3). In separate analyses, the predictive ability of the metabolites was assessed: both the three significantly associated metabolite (ratios) as well as a panel of 35 metabolites selected from all metabolites in an unbiased fashion provided as much but not significantly more prognostic information than selected clinical predictors as judged by the area under the curve. Conclusions. Baseline serum concentrations of spermidine and two metabolite ratios were associated with kidney function change over subsequent years in the general population. In separate analyses, baseline serum metabolites were able to predict incident CKD to a similar but not better extent than selected clinical parameters. Our longitudinal findings provide a basis for targeted studies of certain metabolic pathways, e.g. tryptophan metabolism, and their relation to kidney function decline.

Original languageEnglish
Pages (from-to)2131-2138
Number of pages8
JournalNephrology Dialysis Transplantation
Volume28
Issue number8
DOIs
Publication statusPublished - Aug 2013
Externally publishedYes

Fingerprint

Chronic Renal Insufficiency
Tryptophan
Kynurenine
Kidney
Spermidine
Population
Serum
Incidence
Tandem Mass Spectrometry
Metabolic Networks and Pathways
Phosphatidylcholines
Glomerular Filtration Rate
Liquid Chromatography
Area Under Curve
Odds Ratio
Confidence Intervals
Injections
Health
Research

Keywords

  • GFR
  • Incident chronic kidney disease
  • Kidney function loss
  • Metabolites
  • Prediction

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

Goek, O. N., Prehn, C., Sekula, P., Römisch-Margl, W., Döring, A., Gieger, C., ... Meisinger, C. (2013). Metabolites associate with kidney function decline and incident chronic kidney disease in the general population. Nephrology Dialysis Transplantation, 28(8), 2131-2138. https://doi.org/10.1093/ndt/gft217

Metabolites associate with kidney function decline and incident chronic kidney disease in the general population. / Goek, Oemer Necmi; Prehn, Cornelia; Sekula, Peggy; Römisch-Margl, Werner; Döring, Angela; Gieger, Christian; Heier, Margit; Koenig, Wolfgang; Wang-Sattler, Rui; Illig, Thomas; Suhre, Karsten; Adamski, Jerzy; Köttgen, Anna; Meisinger, Christa.

In: Nephrology Dialysis Transplantation, Vol. 28, No. 8, 08.2013, p. 2131-2138.

Research output: Contribution to journalArticle

Goek, ON, Prehn, C, Sekula, P, Römisch-Margl, W, Döring, A, Gieger, C, Heier, M, Koenig, W, Wang-Sattler, R, Illig, T, Suhre, K, Adamski, J, Köttgen, A & Meisinger, C 2013, 'Metabolites associate with kidney function decline and incident chronic kidney disease in the general population', Nephrology Dialysis Transplantation, vol. 28, no. 8, pp. 2131-2138. https://doi.org/10.1093/ndt/gft217
Goek, Oemer Necmi ; Prehn, Cornelia ; Sekula, Peggy ; Römisch-Margl, Werner ; Döring, Angela ; Gieger, Christian ; Heier, Margit ; Koenig, Wolfgang ; Wang-Sattler, Rui ; Illig, Thomas ; Suhre, Karsten ; Adamski, Jerzy ; Köttgen, Anna ; Meisinger, Christa. / Metabolites associate with kidney function decline and incident chronic kidney disease in the general population. In: Nephrology Dialysis Transplantation. 2013 ; Vol. 28, No. 8. pp. 2131-2138.
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abstract = "Background. Serum metabolites are associated cross-sectionally with kidney function in population-based studies. Methods. Using flow injection and liquid chromatography tandem mass spectrometry methods, we examined longitudinal associations of baseline concentrations of 140 metabolites and their 19 460 ratios with kidney function decline and chronic kidney disease (CKD) incidence over 7 years in 1104 participants of the Cooperative Health Research in the Region of Augsburg S4/F4 study. Results. Corrected for multiple testing, a significant association with annual change in the estimated glomerular filtration rate was observed for spermidine (P = 5.8 × 10-7) and two metabolite ratios, the phosphatidylcholine diacyl C42:5- tophosphatidylcholine acyl-alkyl C36:0 ratio (P = 1.5 × 10-6) and the kynurenine-to-tryptophan ratio (P = 1.9 × 10-6). The kynurenine-to-tryptophan ratio was also associated with significantly higher incidence of CKD at the follow-up visit with an odds ratio of 1.36 per standard deviation increase; 95{\%} confidence interval 1.11-1.66, P = 2.7 × 10 -3). In separate analyses, the predictive ability of the metabolites was assessed: both the three significantly associated metabolite (ratios) as well as a panel of 35 metabolites selected from all metabolites in an unbiased fashion provided as much but not significantly more prognostic information than selected clinical predictors as judged by the area under the curve. Conclusions. Baseline serum concentrations of spermidine and two metabolite ratios were associated with kidney function change over subsequent years in the general population. In separate analyses, baseline serum metabolites were able to predict incident CKD to a similar but not better extent than selected clinical parameters. Our longitudinal findings provide a basis for targeted studies of certain metabolic pathways, e.g. tryptophan metabolism, and their relation to kidney function decline.",
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AU - Sekula, Peggy

AU - Römisch-Margl, Werner

AU - Döring, Angela

AU - Gieger, Christian

AU - Heier, Margit

AU - Koenig, Wolfgang

AU - Wang-Sattler, Rui

AU - Illig, Thomas

AU - Suhre, Karsten

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N2 - Background. Serum metabolites are associated cross-sectionally with kidney function in population-based studies. Methods. Using flow injection and liquid chromatography tandem mass spectrometry methods, we examined longitudinal associations of baseline concentrations of 140 metabolites and their 19 460 ratios with kidney function decline and chronic kidney disease (CKD) incidence over 7 years in 1104 participants of the Cooperative Health Research in the Region of Augsburg S4/F4 study. Results. Corrected for multiple testing, a significant association with annual change in the estimated glomerular filtration rate was observed for spermidine (P = 5.8 × 10-7) and two metabolite ratios, the phosphatidylcholine diacyl C42:5- tophosphatidylcholine acyl-alkyl C36:0 ratio (P = 1.5 × 10-6) and the kynurenine-to-tryptophan ratio (P = 1.9 × 10-6). The kynurenine-to-tryptophan ratio was also associated with significantly higher incidence of CKD at the follow-up visit with an odds ratio of 1.36 per standard deviation increase; 95% confidence interval 1.11-1.66, P = 2.7 × 10 -3). In separate analyses, the predictive ability of the metabolites was assessed: both the three significantly associated metabolite (ratios) as well as a panel of 35 metabolites selected from all metabolites in an unbiased fashion provided as much but not significantly more prognostic information than selected clinical predictors as judged by the area under the curve. Conclusions. Baseline serum concentrations of spermidine and two metabolite ratios were associated with kidney function change over subsequent years in the general population. In separate analyses, baseline serum metabolites were able to predict incident CKD to a similar but not better extent than selected clinical parameters. Our longitudinal findings provide a basis for targeted studies of certain metabolic pathways, e.g. tryptophan metabolism, and their relation to kidney function decline.

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KW - Incident chronic kidney disease

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KW - Metabolites

KW - Prediction

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