Patients with a pronounced ambulatory blood pressure response after renal denervation showed a biomarker profile consistent with higher neurohumoral activation, with higher baseline upright plasma renin activity, 24-h urinary norepinephrine, serum neuropeptide Y, and plasma adenosine triphosphate levels associated with high response.
Key Findings
Results
Renal denervation was associated with significant reductions in both office and ambulatory blood pressure at 6 months.
Office SBP decreased by 21.57 ± 9.90 mmHg and office DBP decreased by 9.70 ± 9.94 mmHg at 6 months.
24-h ambulatory SBP decreased by 14.38 ± 13.55 mmHg and 24-h ambulatory DBP decreased by 9.25 ± 8.57 mmHg at 6 months.
BP reductions were also observed at 24 hours post-procedure.
The study included 40 patients with uncontrolled essential hypertension across four clinical trial programs.
Results
High responders to RDN had higher baseline upright plasma renin activity compared to low responders.
High response was defined as a reduction of ≥10 mmHg in 24-h ambulatory systolic blood pressure at 6 months.
Upright plasma renin activity was identified as one of four key biomarkers differentiating response groups.
Logistic regression confirmed upright plasma renin activity was associated with high response.
Baseline aldosterone levels did not differ between response groups, suggesting renin activity specifically (rather than the full RAAS) was the distinguishing factor.
Results
Higher baseline 24-h urinary norepinephrine levels were associated with high BP response after RDN.
24-h urinary norepinephrine was one of four biomarkers that differed significantly between high- and low-response groups.
This finding is consistent with a profile of higher sympathetic nervous system activation in high responders.
Logistic regression confirmed the association between urinary norepinephrine and high response.
The finding supports the rationale that patients with higher sympathetic activity may derive greater benefit from RDN.
Results
Higher baseline serum neuropeptide Y levels were associated with high BP response after RDN.
Serum neuropeptide Y was one of four candidate biomarkers identified in comparisons between high- and low-response groups.
Neuropeptide Y is a neurohumoral marker co-released with norepinephrine from sympathetic nerve terminals.
The association was confirmed in logistic regression analysis.
This biomarker further supports a profile of heightened sympathetic nervous system activation in high responders.
Results
Higher baseline plasma adenosine triphosphate (ATP) levels were associated with high BP response after RDN.
Plasma ATP was identified as one of four biomarkers differentiating high from low responders.
ATP is a purinergic signaling molecule involved in neurohumoral and autonomic regulation.
The association was confirmed in logistic regression analysis.
This finding adds ATP to the panel of candidate biomarkers characterizing RDN responsiveness.
Results
A combined model of the four biomarkers showed high apparent discrimination between high and low responders to RDN.
The four biomarkers were: upright plasma renin activity, 24-h urinary norepinephrine, serum neuropeptide Y, and plasma ATP.
Receiver operating characteristic (ROC) analyses were performed to evaluate candidate biomarkers.
The combined model demonstrated high apparent discrimination ability.
The authors note that validation in larger prospective cohorts is required before clinical application.
Results
Several baseline clinical and anatomical variables did not differ between high and low responders to RDN.
Baseline sex, age, ablation number, renal artery diameter, renal artery length, and aldosterone levels did not differ between response groups.
BP reductions were broadly comparable across the four catheter subgroups used in the clinical trial programs.
This suggests that procedural and anatomical factors alone do not explain the heterogeneity in BP response.
The study was a single-center post hoc analysis of 40 patients enrolled across four clinical trial programs.
What This Means
Renal denervation (RDN) is a procedure that uses radiofrequency or ultrasound energy to disrupt the nerves surrounding the kidney's arteries, with the goal of lowering blood pressure in patients whose hypertension is not controlled by medications. However, not all patients respond equally well to this treatment. This study examined whether certain biological markers measured in the blood and urine before the procedure could predict who would experience a large drop in blood pressure afterward. Among 40 patients with uncontrolled high blood pressure who underwent RDN, researchers found that those who had the biggest reductions in 24-hour ambulatory blood pressure (at least 10 mmHg lower after 6 months) tended to have higher levels of four specific markers at baseline: plasma renin activity (measured while upright), urinary norepinephrine collected over 24 hours, serum neuropeptide Y, and plasma adenosine triphosphate (ATP). When these four markers were combined into a single model, they showed strong ability to distinguish high from low responders.
This research suggests that patients whose bodies show signs of higher neurohumoral activation — essentially, a more overactive stress-response and hormonal system — may be more likely to benefit from renal denervation. Norepinephrine is a stress hormone released by sympathetic nerves, neuropeptide Y is a chemical co-released alongside it, renin is an enzyme involved in blood pressure regulation, and ATP plays a role in nerve signaling. Together, these markers paint a picture of a nervous system that is working harder than normal to raise blood pressure, which is precisely what RDN is designed to counteract.
The practical implication of these findings is that measuring these biomarkers before the procedure might help doctors identify which patients are most likely to respond well to RDN. However, the study was small (only 40 patients) and was a post hoc analysis of data from multiple trials rather than a prospectively designed study, so the results need to be confirmed in larger, dedicated research before they can be used in clinical decision-making. The authors explicitly call for validation in larger prospective cohorts.
Liang W, Wang Y, Ai L, Sun R, Zhao X, Yu H, et al.. (2026). Neurohumoral Biomarker Profile Associated With Blood Pressure Response After Renal Denervation.. Journal of clinical hypertension (Greenwich, Conn.). https://doi.org/10.1111/jch.70352