Clinical Significance of ADMA and SDMA Tests
ADMA and SDMA are important biomarkers with significant clinical value in cardiovascular disease risk assessment, renal function monitoring, and endothelial dysfunction evaluation.
What are ADMA and SDMA?
- Asymmetric dimethylarginine (ADMA): An endogenously occurring methylarginine that inhibits nitric oxide synthase (NOS), reducing nitric oxide production 1
- Symmetric dimethylarginine (SDMA): ADMA's enantiomer, initially thought to be biologically inactive but now recognized as an excellent marker of renal function 1
Clinical Applications
1. Cardiovascular Disease Risk Assessment
- ADMA is a potent endogenous inhibitor of nitric oxide synthase, causing endothelial dysfunction, vasoconstriction, and aggravation of atherosclerosis 2
- Elevated ADMA levels are associated with:
2. Renal Function Monitoring
- SDMA serves as an outstanding marker of renal function in both humans and animal models 1
- SDMA levels correlate strongly with glomerular filtration rate (GFR) 4
- In chronic kidney disease (CKD) patients, SDMA is an independent predictor for progression to end-stage renal disease 5
- Highest SDMA levels are observed in end-stage renal disease patients on dialysis 1
3. Diabetes and Albuminuria Assessment
- Both ADMA and SDMA are significantly elevated in patients with Type 2 diabetes with micro- and macroalbuminuria compared to those with normoalbuminuria 4
- ADMA correlates significantly with high-sensitivity C-reactive protein (hsCRP) and GFR in diabetic patients 4
4. Pulmonary Hypertension Evaluation
- ADMA is recognized as a marker of vascular dysfunction in pulmonary hypertension, alongside other markers like endothelin-1, angiopoeitins, and von Willebrand factor 3
- The European Society of Cardiology and European Respiratory Society include ADMA among biochemical markers that can be explored in pulmonary hypertension assessment 3
Interpretation of Results
Elevated ADMA levels indicate:
- Increased cardiovascular risk
- Potential endothelial dysfunction
- Possible renal dysfunction
- Chronic inflammation (correlates with hsCRP) 4
Elevated SDMA levels indicate:
Clinical Considerations
Both ADMA and SDMA should be interpreted in the context of other clinical and laboratory findings
ADMA levels can be influenced by:
- Renal function
- Inflammatory status
- Homocysteine levels 3
- ADMA/SDMA ratio may provide additional clinical information beyond individual values
In patients with homocysteinemia, ADMA elevation may be related to:
- Activation of arginine-protein-methyltransferases
- Down-regulation of dimethylarginine-dimethylaminohydrolase 3
Potential Therapeutic Implications
Monitoring ADMA/SDMA in patients with:
- Chronic kidney disease
- Cardiovascular disease
- Diabetes with albuminuria
- Pulmonary hypertension
Therapeutic strategies targeting ADMA reduction may include:
- Folate administration (0.5-5.0 mg/day) with vitamin B12 (0.02-1 mg/day) to reduce homocysteine levels, which may indirectly affect ADMA 3
- L-arginine supplementation to overcome competitive inhibition of NOS by ADMA
Limitations and Caveats
- Some studies suggest paradoxical findings where lower ADMA levels were associated with cardiovascular events in certain CKD populations 5
- The clinical utility of routine ADMA/SDMA testing is still evolving and not yet part of standard clinical practice guidelines for most conditions
- Laboratory methods for measuring ADMA and SDMA (typically high-performance liquid chromatography) may not be widely available in all clinical settings
In conclusion, ADMA and SDMA tests provide valuable information about cardiovascular risk, renal function, and endothelial health. They are particularly useful in patients with chronic kidney disease, cardiovascular disease, and diabetes with albuminuria, where they can help assess disease progression and prognosis.