Biomarkers of Inflammation and Oxidation: SDMA

Optimal Takeaways

Symmetric dimethylarginine (SDMA) is a potentially toxic compound produced in the body. It promotes inflammation and can interfere with nitric oxide metabolism, leading to endothelial dysfunction and increased cardiovascular disease and mortality.

SDMA is excreted by the kidneys and is considered a reliable marker of renal function. Elevated levels are also associated with inflammation, hypertension, cardiovascular disease, stroke, pregnancy complications, and all-cause mortality risk. Low levels suggest adequate renal clearance and a reduced risk of cardiovascular disease.

Standard Range: 73 - 135 ng/mL (0.36 – 0.67 umol/L)

The ODX Range: 0.00 – 135 ng/mL (0.00 – 0.67 umol/L)

Low SDMA is associated with adequate renal function and decreased cardiovascular and inflammatory risk.

High SDMA levels are associated with end-stage renal disease (Oliva-Damaso 2019), acute kidney injury, endothelial dysfunction, hypertension, CAD, hyperuricemia, diabetes mellitus, stroke, PCOS, preeclampsia (Tain 2017), inflammation (Schepers 2011), increased risk of all-cause mortality and cardiovascular disease (Schlesinger 2016).

Overview

Symmetric dimethylarginine (SDMA), like ADMA, is a modified form of arginine generated intracellularly from nuclear proteins versus directly from free arginine. However, whereas ADMA is primarily broken down enzymatically, SDMA is eliminated mainly in the urine and can build up when kidney function is compromised. SDMA is considered an outstanding marker of renal function. SDMA and ADMA are both independent risk factors for CVD and all-cause mortality, especially in the general population. SDMA is also associated with inflammatory markers IL-6 and TNF-alpha and can adversely modify HDL and contribute to endothelial dysfunction and atherosclerosis (Oliva-Damaso 2019).

SDMA also activates NF-kappa B, further enhancing IL-6, TNF-alpha, and the inflammatory process in chronic kidney disease. SDMA levels above 226 ng/mL (1.12 umol/L) were associated with significantly higher IL-6, TNF-alpha, CRP, phosphate, and ADMA and significantly lower albumin and hemoglobin compared to an SDMA of 226 ng/mL or below. ADMA may not stimulate inflammatory markers the way SDMA does (Schepers 2011).

Although SDMA does not appear to affect endothelial nitric oxide synthase directly, it does compete directly with arginine, therefore reducing the synthesis of nitric oxide in a dose-dependent manner (Gamil 2020). Ultimately, the pro-oxidant and pro-inflammatory nature of SDMA contributes to its association with cardiovascular disease and all-cause mortality (Tain 2017).

A meta-analysis concluded that cardiovascular risk increased by 5% and all-cause mortality risk by 7% for each 20 ng/mL (0.1 umol/L) increase in circulating ADMA, and increased by 3% and 4%, respectively for SDMA levels (Schlesinger 2016).

Levels of both SDMA and ADMA are associated with the severity of sepsis and are significantly higher in non-survivors versus survivors. In one prospective study of 120 ICU patients, non-survivors had a median SDMA of 230.28 vs. 165.64 ng/mL (1.14 vs. 0.82 umol/L) and a median ADMA of 187.86 vs. 145.44 ng/mL (0.93 vs. 0.72 umol/L). The highest mortality was observed in those with an SDMA level above 270.68 ng/mL (1.34 umol/L) and an ADMA above 195.94 ng/mL (0.97 umol/L) (Winkler 2018).

ADMA and SDMA metabolism

Source: Oliva-Damaso, Elena et al. “Asymmetric (ADMA) and Symmetric (SDMA) Dimethylarginines in Chronic Kidney Disease: A Clinical Approach.” International journal of molecular sciences vol. 20,15 3668. 26 Jul. 2019, doi:10.3390/ijms20153668 This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

References  

Gamil, Sahar et al. “Increased Serum Levels of Asymmetric Dimethylarginine and Symmetric Dimethylarginine and Decreased Levels of Arginine in Sudanese Patients with Essential Hypertension.” Kidney & blood pressure research vol. 45,5 (2020): 727-736. doi:10.1159/000508695 

Oliva-Damaso, Elena et al. “Asymmetric (ADMA) and Symmetric (SDMA) Dimethylarginines in Chronic Kidney Disease: A Clinical Approach.” International journal of molecular sciences vol. 20,15 3668. 26 Jul. 2019, doi:10.3390/ijms20153668 

Schepers, Eva et al. “Symmetric dimethylarginine as a proinflammatory agent in chronic kidney disease.” Clinical journal of the American Society of Nephrology : CJASN vol. 6,10 (2011): 2374-83. doi:10.2215/CJN.01720211 

Schlesinger, Sabrina et al. “Asymmetric and Symmetric Dimethylarginine as Risk Markers for Total Mortality and Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Prospective Studies.” PloS one vol. 11,11 e0165811. 3 Nov. 2016, doi:10.1371/journal.pone.0165811

Tain, You-Lin, and Chien-Ning Hsu. Toxic Dimethylarginines: Asymmetric  Dimethylarginine (ADMA) and Symmetric  Dimethylarginine (SDMA).” Toxins vol. 9,3 92. 6 Mar. 2017, doi:10.3390/toxins9030092

Winkler, Martin Sebastian et al. “Symmetrical (SDMA) and asymmetrical dimethylarginine (ADMA) in sepsis: high plasma levels as combined risk markers for sepsis survival.” Critical care (London, England) vol. 22,1 216. 19 Sep. 2018, doi:10.1186/s13054-018-2090-1