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Updated: Jul 29, 2025
Exploring the Arginine Methylome by Nuclear Magnetic Resonance Spectroscopy
Published on: December 16, 2021
Plasma arginine metabolites in health and chronic kidney disease
Amy Y M Au1,2, Kevin Mantik3, Forough Bahadory3
1Department of Nephrology, Prince of Wales Hospital, Sydney, NSW, Australia.
Insights
Elevated levels of asymmetric and symmetric dimethylarginine (ADMA and SDMA) are linked to chronic kidney disease (CKD) risk. Measuring these methylarginines can help identify individuals at high risk for CKD progression.
Area of Science:
- Nephrology
- Biochemistry
- Cardiovascular Medicine
Background:
- Elevated plasma levels of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) are established risk factors for chronic kidney disease (CKD) and cardiovascular disease.
- Plasma cystatin C (pCYSC)-based estimated glomerular filtration rate (eGFR) trajectories identified a high-risk cohort within the Dunedin Multidisciplinary Health and Development Study (DMHDS).
Purpose of the Study:
- To investigate the association between methylarginine metabolites (ADMA, SDMA, L-arginine, L-citrulline) and kidney function in the DMHDS cohort.
- To determine if methylarginine concentrations can predict the risk of poor kidney health outcomes.
Main Methods:
- Plasma concentrations of ADMA, SDMA, L-arginine, and L-citrulline were quantified using liquid chromatography-tandem mass spectrometry in 45-year-old DMHDS participants.
- Associations between methylarginines, serum creatinine, pCYSC, and eGFR were analyzed.
- Methylarginine levels were compared between a healthy subset, the total cohort, and a separate cohort with established CKD.
Main Results:
- In a healthy subset, mean concentrations were ADMA (0.40 ± 0.06 µmol/L) and SDMA (0.42 ± 0.06 µmol/L).
- In the total cohort, SDMA showed positive correlations with serum creatinine (r=0.55) and pCYSC (r=0.55), and a negative correlation with eGFR (r=0.52).
- Patients with stage 3-4 CKD exhibited significantly higher mean ADMA, SDMA, and L-citrulline levels. ADMA and SDMA individually predicted high-risk of poor kidney health outcomes with AUCs of 0.83 and 0.84, respectively, achieving an AUC of 0.90 when combined.
Conclusions:
- Plasma methylarginine concentrations, specifically ADMA and SDMA, are significantly associated with kidney function markers.
- These metabolites effectively stratify individuals at high risk for CKD progression.
- Methylarginine measurements offer a promising tool for early risk assessment in kidney disease.
Background:
Elevated plasma asymmetric and symmetric dimethylarginine (ADMA and SDMA) are risk factors for chronic kidney disease (CKD) and cardiovascular disease. Using plasma cystatin C (pCYSC)-based estimated glomerular filtration rate (eGFR) trajectories, we identified a cohort at high risk of poor kidney-related health outcomes amongst members of the Dunedin Multidisciplinary Health and Development Study (DMHDS). We therefore examined associations between methylarginine metabolites and kidney function in this cohort.
Methods:
ADMA, SDMA, L-arginine and L-citrulline were measured in plasma samples from 45-year-olds in the DMHDS cohort by liquid chromatography-tandem mass spectrometry.
Results:
In a healthy DMHDS subset (n = 376), mean concentrations were: ADMA (0.40 ± 0.06 µmol/L), SDMA (0.42 ± 0.06 µmol/L), L-arginine (93.5 ± 23.1 µmol/L) and L-citrulline (24.0 ± 5.4 µmol/L). In the total cohort (n = 857), SDMA correlated positively with serum creatinine (Pearson's r = 0.55) and pCYSC (r = 0.55), and negatively with eGFR (r = 0.52). A separate cohort of 38 patients with stage 3-4 CKD (eGFR 15-60 mL/min/1.73 m2) confirmed significantly higher mean ADMA (0.61 ± 0.11 µmol/L), SDMA (0.65 ± 0.25 µmol/L) and L-citrulline (42.7 ± 11.8 µmol/L) concentrations. DMHDS members classified as high-risk of poor kidney health outcomes had significantly higher mean concentrations of all four metabolites compared with individuals not at risk. ADMA and SDMA individually predicted high-risk of poor kidney health outcomes with areas under the ROC curves (AUCs) of 0.83 and 0.84, and together with an AUC of 0.90.
Conclusions:
Plasma methylarginine concentrations facilitate stratification for risk of CKD progression.
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