Editor’s note: The National Kidney Foundation sponsored a session on this topic at its 2012 Spring Clinical Meetings in National Harbor, Md. The moderators were George L. Bakris, MD, Professor of Medicine and Director, ASH Comprehensive Hypertension Center, The University of Chicago Medicine, and Joseph A. Vassalotti, MD, Chief Medical Officer, NKF, and Associate Clinical Professor of Medicine, Mount Sinai School of Medicine. What follows is a summation of the presentations given during the session.

Despite recent advances in the treatment of hypertension, the majority of patients with chronic kidney disease (CKD) still remain above current blood pressure (BP) targets. Improved BP control is expected to slow progression of loss of kidney function as well as reduce the incidence of cardiovascular events and death.

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Data from NHANES 1999-2004 show adults with CKD are less likely to have awareness, treatment, and control of BP than those without evidence of CKD.1 The inability to achieve goal BP despite three or more antihypertensive drugs is defined as resistant hypertension, and this is more common in CKD patients.

Practice Guidelines

The National Heart, Lung and Blood Institute’s Joint National Committee (JNC) 7 2 and National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (KDOQI) clinical practice guidelines3 currently recommend targets lower than 130/80 mm Hg in CKD patients.

However, updated BP guidelines from KDIGO to be published this year suggest the level of evidence to support this target varies by the presence or absence of diabetes and the level of albuminuria in this patient population.

In fact, a recent systematic review of the literature revealed only three randomized controlled trials in which patients with CKD achieved a BP lower than 130/80 mm Hg.4 None of these trials included patients with diabetes, and two of the three trials showed a benefit in terms of slowing CKD progression only in the sub-groups with more than one gram of proteinuria with minor increases in both the number of anti-hypertensive drugs used and adverse effects.

Data from more than 16,000 participants in the National Kidney Foundation’s Kidney Early Evaluation Program (KEEP) show associations between BP levels and end-stage renal disease (ESRD), or chronic kidney failure, in patients with stage 3 and stage 4 CKD. A higher risk for developing ESRD was observed among people with BP measurements of 140/90 or higher, but those who had BP measurements of 150/90 and above were at highest risk.

Additionally, the study found that that more than 30% of people with CKD had BP measurements above 150/90. This study highlights the importance of BP control in CKD patients, suggesting that a target of 140/90 may suffice at least in terms of delaying progression to chronic kidney failure.5  

Innovative strategies are needed to lower BP in patients with CKD. Novel approaches to hypertension treatment reviewed subsequently include: baroreceptor sensitization and renal nerve ablation.

Baroreceptor Modulation for Refractory Hypertension

The Rheos Baroreflex Hypertension Therapy System is an implantable device that can treat patients with resistant hypertension. It activates the carotid baroreflex through electrical stimulation of the carotid sinus wall. The Rheos Pivotal Trial is a randomized, double-blind, parallel-design, phase 3 trial of baroreflex activation therapy (BAT) on systolic blood pressure (SBP) in 265 patients with resistant hypertension.6 Subjects received either BAT (Group A) for the first six months or delayed BAT initiation following the six-month visit (Group B).

The five coprimary endpoints were:

  • acute SBP responder rate at six months
  • sustained responder rate at 12 months
  • procedure safety
  • BAT safety
  • device safety

The trial showed significant benefit for the endpoints of sustained efficacy, BAT safety, and device safety. However, it did not meet the endpoints for acute responders or procedural safety. A protocol-specified ancillary analysis showed 42% of patients in Group A achieved an SBP of 140 mm Hg or less at six months compared with 24% of Group B, a statistically significant difference between the groups. Both groups achieved an SBP of 140 mm Hg or higher at 12 months.

A non-randomized unblinded follow up of the Rheos Pivotal Trial revealed that 76% of subjects qualified as clinically significant responders, and an additional 10% were indeterminate.7 Among long-term responders receiving BAT, the mean BP drop was 35/16 mm Hg. Medication use was reduced by the end of the randomized phase and remained lower through the follow-up period.

Among responders, 55% achieved goal BP (less than 140 or less than 130 mm Hg in patients with diabetes or kidney disease). BP measurements of all active patients remained stable from completion of the randomized phase through long-term follow-up. BAT substantially reduced arterial pressure for most patients participating in the Rheos Pivotal Trial, which was maintained over long-term follow-up of 22 to 53 months.