What are the benefits of renal denervation in older adults with chronic kidney disease (CKD) and resistant hypertension who have failed to achieve adequate blood pressure control with optimal medical therapy?

Renal Denervation in CKD: Current Evidence and Recommendations

Primary Recommendation

Renal denervation should NOT be used as routine treatment for resistant hypertension in older adults with CKD, as current guidelines classify it as investigational without proven cardiovascular benefits or mortality reduction. 1

Guideline-Based Position

The most recent authoritative guidance establishes clear limitations:

• The European Society of Cardiology explicitly states that renal denervation is NOT a first-line blood pressure-lowering intervention due to lack of adequately powered outcomes trials demonstrating safety and cardiovascular disease benefits 1

• Device-based therapies including renal denervation are NOT recommended for routine hypertension treatment unless within the context of clinical studies and randomized controlled trials 1

• The procedure remains classified as investigational for uncontrolled hypertension treatment 1

• The landmark SYMPLICITY HTN-3 trial—the first large-scale sham-controlled study—showed no significant difference in systolic blood pressure reduction between renal denervation and sham procedure, leaving the future of this intervention uncertain 2

Evidence Quality Assessment

Blood Pressure Effects

• Moderate quality evidence demonstrates NO significant effect on blood pressure control when compared to control interventions 3
  • 24-hour ambulatory systolic BP: MD 0.28 mmHg (95% CI -3.74 to 4.29) 3
  • Office systolic BP: MD -4.08 mmHg (95% CI -15.26 to 7.11) 3
  • These differences are clinically insignificant

Cardiovascular Outcomes

• Low quality evidence shows NO reduction in major cardiovascular events 3:
  • Myocardial infarction: RR 1.31 (95% CI 0.45 to 3.84) 3
  • Ischemic stroke: RR 1.15 (95% CI 0.36 to 3.72) 3
  • Unstable angina: RR 0.63 (95% CI 0.08 to 5.06) 3

Renal Function

• Low quality evidence suggests NO effect on kidney function 3:
  • Serum creatinine: MD 0.01 mg/dL (95% CI -0.12 to 0.14) 3
  • eGFR/creatinine clearance: MD -2.09 mL/min (95% CI -8.12 to 3.95) 3

Safety Concerns

• Low quality evidence shows significantly increased bradycardia episodes: RR 6.63 (95% CI 1.19 to 36.84) compared to control 3

Critical Limitations of Observational Data

While some observational studies suggest potential benefits in CKD populations 4, 5, 6, these findings must be interpreted with extreme caution:

• The 2015 observational study showing eGFR improvement 4 lacks a control group and represents only 27 patients—insufficient to override negative sham-controlled trial data
• Meta-analyses of uncontrolled studies 5 cannot establish causation and are prone to publication bias
• Registry data 6 showing BP reductions lack the rigor of randomized sham-controlled trials

Recommended Management Algorithm for CKD with Resistant Hypertension

Instead of renal denervation, prioritize these evidence-based interventions:

1. Intensify lifestyle modifications, particularly sodium restriction to <2g/day 1

2. Add low-dose spironolactone (12.5-25mg daily) to existing regimen, which is specifically recommended for resistant hypertension 1

   • Monitor potassium and renal function closely given CKD 2

3. Optimize diuretic therapy addressing volume expansion, which is the primary mechanism of treatment resistance in CKD 2

4. Screen for secondary causes, particularly:

   • Renal artery stenosis (especially in older patients with atherosclerotic disease) 2
   • Primary aldosteronism 2

5. Ensure medication adherence and exclude white-coat effect with 24-hour ambulatory BP monitoring 2

When Renal Denervation Might Be Considered

Only in highly selected circumstances:

• Within the context of a clinical trial or research protocol 1
• At medium-to-high volume centers with appropriate expertise 1
• After exhausting all medical therapy options including spironolactone 1
• With full informed consent regarding investigational status and lack of proven benefit on hard outcomes 3

Critical Pitfalls to Avoid

• Do not offer renal denervation as standard care for resistant hypertension in CKD patients 1
• Do not assume BP reduction equals cardiovascular benefit—the procedure has not demonstrated mortality or morbidity reduction 3
• Do not overlook volume overload as the primary driver of resistant hypertension in CKD, which requires aggressive diuretic therapy rather than procedural intervention 2
• Do not proceed without excluding secondary causes of hypertension that have specific treatments 2