New findings reshape how we view blood markers in CKD and cardiovascular risk
When researchers at the University of Texas at Arlington set out to understand why people with chronic kidney disease (CKD) often die from heart problems rather than kidney failure, they revisited a long-standing assumption about blood markers. For years, scientists highlighted ADMA (asymmetric dimethylarginine) as a warning sign for vascular problems. But a recent study, published in the American Journal of Physiology-Renal Physiology, points to a different player: SDMA (symmetric dimethylarginine).
The team’s results suggest that SDMA, long considered largely inactive in the cardiovascular equation, may be more closely tied to vascular health in CKD than ADMA. These findings add a new layer to how clinicians think about monitoring vascular function in patients whose kidneys aren’t working at full capacity.
Rethinking SDMA and ADMA in CKD
ADMA has long been viewed as a potential predictor of blood vessel dysfunction because it interferes with nitric oxide production, a key factor in vascular health. The UT Arlington researchers, led by Paul J. Fadel of the Human Neural Cardiovascular Control Lab, aimed to better understand this link by examining blood vessel function in people with CKD. What they found challenged the conventional wisdom: SDMA’s association with vascular health was stronger than anticipated, at least in the subset of patients with moderate CKD (primarily stage 3).
Even though SDMA is strongly related to kidney function, the study revealed that higher SDMA levels correlated with weaker blood vessel function, suggesting that SDMA could flag early vascular problems before the condition progresses to the point where dialysis becomes necessary. In contrast, ADMA’s connection to vascular function was not as consistently observed in this particular group.
Why stage 3 CKD was the focus
The researchers specifically looked at patients with moderate disease because this stage is a window of opportunity for intervention. If vascular risk can be identified earlier, clinicians may implement strategies to offset cardiovascular complications as CKD advances and dialysis looms on the horizon.
Key findings and their implications
In the study, SDMA emerged as a more reliable correlate of vascular dysfunction than ADMA among CKD patients who had not yet progressed to more advanced kidney failure. The takeaway is not that SDMA is a perfect predictor, but that it offers a potentially valuable signal about cardiovascular risk that could complement existing assessments. Dr. Fadel emphasized that while the associations were noteworthy, they were modest in strength, calling for further research to determine how SDMA testing could be integrated into routine care.
“The background premise of the study is that people with chronic kidney disease do not die from their kidney problems. They die from cardiovascular disease,” Fadel noted. “We wanted to better understand that connection by examining blood vessel function.” The data suggest SDMA could become part of a broader toolkit to monitor vascular health in CKD patients, particularly those in the middle stages of the disease.
Clinical implications and caveats
Clinically, the findings offer a potential shift in how doctors track cardiovascular risk in CKD. Measuring SDMA levels could help identify at-risk patients earlier, enabling targeted interventions that might slow the onset of vascular dysfunction. However, the researchers caution that SDMA should not be viewed as a standalone predictor. The relationship between SDMA and vascular health is modest, and SDMA is only one piece of a complex puzzle that includes kidney function, blood pressure, lipid levels, inflammation, and other factors.
In practice, SDMA could complement existing tests and risk scores, prompting more personalized monitoring for patients with CKD, especially those in stage 3. The study also underscores the need for replication and expansion across diverse patient populations and CKD stages to determine how best to apply SDMA measurements in clinical decision-making.
What comes next for research and care
Fadel and colleagues are planning further work to validate these observations in larger cohorts and across CKD stages. Additional research will assess how SDMA behaves in conjunction with other biomarkers and whether interventions that improve vascular health can modify SDMA’s predictive value. The evolving picture may eventually lead to integrated biomarker panels that better forecast cardiovascular risk in CKD than any single marker alone.
About the researchers
Paul J. Fadel, who heads UT Arlington’s Human Neural Cardiovascular Control Lab, led the study. The research team included UT Arlington postdoctoral fellows and doctoral students, along with physician collaborator Ponnaiah Mohan, illustrating a collaborative approach to untangling the links between kidney function and heart health.
Bottom line for patients and clinicians
While SDMA’s role as a predictor of cardiovascular risk in CKD is not yet definitive, the findings open a promising avenue for early identification of vascular problems. As science advances, SDMA testing could become part of a broader strategy to monitor and protect heart health in people living with CKD, potentially guiding earlier interventions before kidney disease progresses to dialysis-dependent stages.
