Amino Acids

, Volume 50, Issue 10, pp 1347–1356 | Cite as

l-Homoarginine and its AGXT2-metabolite GOCA in chronic kidney disease as markers for clinical status and prognosis

  • Jens Martens-LobenhofferEmail author
  • Insa E. Emrich
  • Adam M. Zawada
  • Danilo Fliser
  • Stefan Wagenpfeil
  • Gunnar H. Heine
  • Stefanie M. Bode-Böger
Original Article


Plasma concentrations of l-homoarginine (hArg) are an emerging marker for clinical status and prognosis in renal and cardiovascular disease. Lowered hArg concentrations are associated with higher risk for these conditions, although a clear pathophysiological explanation for this association has not been established. Baseline plasma samples of patients with different stages of chronic kidney disease (CKD) (n = 527) were obtained from the CARE FOR HOMe study and were analyzed for hArg and, for the first time, its metabolite 6-guanidino-2-oxocaproic acid (GOCA) by isotope dilution LC–MS/MS methods. GOCA is converted from hArg by the enzyme alanine:glyoxylate aminotransferase 2 (AGXT2), which is also in the focus of current cardiovascular research. hArg levels ranged from 0.20–4.01 µmol/L with a median of 1.42 µmol/L, whereas GOCA levels were 0.08–25.82 nmol/L with a median of 1.45 nmol/L. hArg levels in the highest tertile (≥ 1.71 µmol/L) were associated with significantly lower risk for reaching the renal (hazard ratio 0.369, 95% confidence interval 0.028–0.655) or cardiovascular (HR 0.458, CI 0.295–0.712) endpoints in univariate Cox regression analysis. Inversely, GOCA levels in the highest tertile (≥ 2.13 nmol/L) were associated with increased renal (HR 3.807, CI 1.963–7.381) and cardiovascular (HR 1.611, CI 1.041–2.495) risk. A decreased ratio between hArg and GOCA predicted even more pronounced the risks for renal (HR 0.178, CI 0.087–0.363) and cardiovascular (HR 0.447, CI 0.281–0.709) events. However, adjustment for the confounders eGFR and albuminuria attenuated these findings. A pathophysiological role of an increased activity of AGXT2 in CKD should be evaluated in future clinical studies.


l-Homoarginine GOCA AGXT2 Human plasma LC–MS/MS 



The present work was supported by a grant from the Else Kröner-Fresenius-Stiftung.

Compliance with ethical standards

Conflict of interest

The authors declare that they do not have any conflict of interest.

Research involving human participants and/or animals

This study involved human participants. It was approved by the local Ethics Committee and was conducted according to the Declaration of Helsinki.

Informed consent

All participants enrolled in this study provided written informed consent according to the Declaration of Helsinki.


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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute of Clinical PharmacologyOtto-von-Guericke UniversityMagdeburgGermany
  2. 2.Internal Medicine IV, Nephrology and HypertensionSaarland University Medical CenterHomburgGermany
  3. 3.Institute for Medical Biometry, Epidemiology and Medical Informatics, Faculty of MedicineSaarland UniversityHomburgGermany

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