L-Homoarginine and its AGXT2-metabolite GOCA in chronic kidney disease as markers for clinical status and prognosis
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:50 |
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| Enthalten in: |
Amino acids - 50(2018), 10 vom: 07. Okt., Seite 1347-1356 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Martens-Lobenhoffer, Jens [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 05.11.2018 Date Revised 26.11.2018 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s00726-018-2610-y |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM286256746 |
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| 100 | 1 | |a Martens-Lobenhoffer, Jens |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a L-Homoarginine and its AGXT2-metabolite GOCA in chronic kidney disease as markers for clinical status and prognosis |
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| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a AGXT2 | |
| 650 | 4 | |a GOCA | |
| 650 | 4 | |a Human plasma | |
| 650 | 4 | |a L-Homoarginine | |
| 650 | 4 | |a LC–MS/MS | |
| 650 | 7 | |a 6-guanidino-2-oxocaproic acid |2 NLM | |
| 650 | 7 | |a Biomarkers |2 NLM | |
| 650 | 7 | |a Caproates |2 NLM | |
| 650 | 7 | |a Guanidines |2 NLM | |
| 650 | 7 | |a Homoarginine |2 NLM | |
| 650 | 7 | |a 156-86-5 |2 NLM | |
| 650 | 7 | |a Transaminases |2 NLM | |
| 650 | 7 | |a EC 2.6.1.- |2 NLM | |
| 650 | 7 | |a Alanine-glyoxylate transaminase |2 NLM | |
| 650 | 7 | |a EC 2.6.1.44 |2 NLM | |
| 700 | 1 | |a Emrich, Insa E |e verfasserin |4 aut | |
| 700 | 1 | |a Zawada, Adam M |e verfasserin |4 aut | |
| 700 | 1 | |a Fliser, Danilo |e verfasserin |4 aut | |
| 700 | 1 | |a Wagenpfeil, Stefan |e verfasserin |4 aut | |
| 700 | 1 | |a Heine, Gunnar H |e verfasserin |4 aut | |
| 700 | 1 | |a Bode-Böger, Stefanie M |e verfasserin |4 aut | |
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