PHILADELPHIA (FRONTLINE MEDICAL NEWS)– Dual blockade of the renin-angiotensin-aldosterone system with combined angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy was no more effective for maintaining blood pressure control than was ACE inihibitor monotherapy in patients with moderately advanced autosomal dominant polycystic kidney disease and stage 3 chronic kidney disease.

That finding emerged from a study of the randomized placebo-controlled Halt Progression of Polycystic Kidney Disease (HALD-PKD) trial reported at Kidney Week 2014.

The composite primary outcome of time to death, end-stage renal disease, or 50% reduction from baseline in estimated glomerular filtration rate (eGFR) was similar in 242 patients with stages 1-3 autosomal dominant polcystic kidney disease (ADPKD) randomized to receive lisinopril plus placebo, and in 243 such patients randomized to receive lisinopril plus telmisartan (number of events in the groups, respectively, 116 and 115; hazard ratio, 1.08), said Dr. Vicente E. Torres.

Also, no significant differences were seen between the groups with respect to the individual components of the composite outcome; the hazard ratios for death, end-stage renal disease, and 50% reduction in eGFR were 0.93, 0.78, and 1.05, respectively, Dr. Torres of the Mayo Clinic College of Medicine, Rochester, Minn. said at the meeting, which was sponsored by the American Society of Nephrology.

The findings were simultaneously published online Nov. 15 in the New England Journal of Medicine ( N Engl J Med 2014 Nov. 15[doi: 10.1056/NEJMoa1402686 ]).

The rates of change in eGFR urinary albumin excretion, and other secondary outcomes and adverse events, including hyperkalemia and acute kidney injury, also were similar in the two groups, Dr. Torres said.

Participants in the double-blind study were enrolled from February 2006 through June 2009. They were aged 18 to 64 years and had eGFR of 25 to 60 ml per minute per 1.73 m2 of body-surface area. Lisinopril doses in both groups were adjusted to achieve a blood pressure of 110/70 to 130/80 mm Hg, and patients were followed for a mean of 5 years. Systolic blood pressures and mean arterial pressures remained within the target range throughout the trial in 73% to 86% and in 70% to 83% of participants, respectively. Diastolic pressures were in the target range in 56% to 65% of participants.

Hypertension develops early and contributes to the progression of disease in patients with ADPKD, and the renin-angiotensin-aldosterone system (RAAS) is implicated in the pathogenesis of hypertension in ADPKD patients. Angiotensin-converting enzyme inhibitors like lisinopril are known to slow the progression of renal dysfunction in non-diabetic kidney disease, and thus have become standard first-line agents for the treatment of hypertension in patients with ADPKD, Dr. Torres said.

“Although ACE inhibitors have become the first-line therapy for hypertension in patients with chronic kidney disease, including ADPKD, their renoprotective effect may be limited by compensatory-feedback increases in renin release and the generation of angiotensin,” he and his colleagues wrote, noting that dual RAAS blockade has been proposed as a strategy to circumvent this compensatory feedback.

The current study showed that adding telmisartan did result in slightly lower blood pressures, but did not reduce the incidence of primary or secondary outcomes.

Both combination therapy and lisinopril monotherapy were safe, with a similar rate of adverse events in the two groups, but the addition of an ARB did not confer additional benefit, Dr. Torres said, concluding that ACE inhibitor monotherapy achieved excellent standard blood pressure control in more than 70% of patients with stages 1-3 ADPKD.The HALT-PKD trial was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (including a grant to Dr. Torres), the National Center for Research Resources’ General Clinical Research Centers, the National Center for Advancing Translational Sciences’ Clinical and Translational Science Awards, the Zell Family Foundation, and the PKD Foundation.


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