Lower BP slows disease process in early PKD

PHILADELPHIA – Dual blockade of the renin-angiotensin-aldosterone system with combined angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy was no more effective than ACE inhibitor therapy alone for slowing the rate of increase in total kidney volume in patients with early autosomal dominant polycystic kidney disease, investigators have reported.

Notably, though, aggressive blood pressure control, as compared with standard control, was associated with a slower rate of increase in total kidney volume in study A of the Halt Progression of Polycystic Kidney Disease (HALT-PKD) trial, Dr. Arlene B. Chapman reported at Kidney Week 2014.

Participants in the randomized, placebo-controlled 2x2 factorial trial were 423 hypertensive patients aged 15 to 49 years who had an estimated glomerular filtration rate (eGFR) of greater than 60 ml/min/1.73 m² of body surface area. They were enrolled at 7 sites from February 2000 through June 2009, underwent a 2-4 week washout period during which antihypertensive therapy was discontinued and clonidine and labetalol therapy was maintained, and were randomized to receive either lisinopril plus telmisartan, or lisinopril plus placebo. They were also randomized to a standard blood pressure target of 120/70 to 130/80 mm Hg, or to a low blood pressure target of 95/60 to 110/75 mm Hg. Treatment doses were adjusted to achieve the target blood pressure, said Dr. Chapman of Emory University, Atlanta.

With respect to dual blockade of the renin-angiotensin-aldosterone system (RAAS) and the primary outcome of percentage change in total kidney volume over time, the rate of total kidney volume increase was similar at 6.0% and 6.2% per year in the lisinopril plus telmisartan group and the lisinopril plus placebo group, respectively, according to findings simultaneously published online Nov. 15 in the New England Journal of Medicine, which showed that total kidney volume increased by 40.5% and 42.2% at 60 months in the groups, respectively (N Engl J Med 2014 Nov. 15[doi:10.1056/NEJMoa1402685])

With respect to the standard vs. low blood pressure target, which was the focus of Dr. Chapman’s talk, significant differences were seen in systolic and diastolic blood pressure, with a difference of 13.4 mm Hg and 9.3 mm Hg, respectively, between the groups at the end of the trial, she said.

“Urinary aldosterone levels decreased significantly in both groups. However, there were no differences in the levels of change between the low and standard blood pressure groups,” she said.

The low target group had a 14.2% slower annual increase in total kidney volume at the end of the study as compared with those in the standard blood pressure target group (annualized change of 5.57% in the low target group vs. 6.57% in the standard target group), she said.

Overall, the change in eGFR did not differ between the groups. Urinary albumin excretion and left ventricular mass declined significantly more in the low vs. standard blood pressure control group, and renal vascular resistance remained the same in the low blood pressure control group, but increased in the standard blood pressure control group.

During a mean follow-up of 5 years, no differences were seen between the groups in the rate of hyperkalemia, acute kidney injury, hospitalizations, cardiac-related hospitalizations or mortality, and the event rates were low, she noted.

“Polycystic kidney disease is the fourth leading cause of renal failure in the United States. It is characterized by renal cyst growth with increased total kidney volume, resulting in activation of the renin-angiotensin system, the development of hypertension early, and progression to renal failure. To date there is no evidence that blood pressure control or blockade of the renin-angiotensin-system slows the progression of renal disease,” she said.

This portion of the HALT-PKD trial showed that both dual blockade of the RAAS and rigorous blood pressure control were safe, but that dual blockade provides no benefit as compared with lisinopril monotherapy with regard to change in total kidney volume and eGFR.

Aggressive blood pressure control, however, was of benefit.

“Low blood pressure treatment in young, healthy, hypertensive polycystic kidney disease patients with blockade of the renin-angiotensin-system was well-tolerated and safe and resulted in a 14.2% slower rate of total kidney volume growth over 5 years, reduced left ventricular mass index, urinary albumin secretion, and renal vascular resistance. This is without impact overall on the change in kidney function,” she concluded.

The HALT-PKD trial was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (including a grant to Dr. Chapman), 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. Detailed author disclosures are available with the full text of the HALT-PKD study at NEJM.org.

PHILADELPHIA – Dual blockade of the renin-angiotensin-aldosterone system with combined angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy was no more effective than ACE inhibitor therapy alone for slowing the rate of increase in total kidney volume in patients with early autosomal dominant polycystic kidney disease, investigators have reported.

Notably, though, aggressive blood pressure control, as compared with standard control, was associated with a slower rate of increase in total kidney volume in study A of the Halt Progression of Polycystic Kidney Disease (HALT-PKD) trial, Dr. Arlene B. Chapman reported at Kidney Week 2014.

Participants in the randomized, placebo-controlled 2x2 factorial trial were 423 hypertensive patients aged 15 to 49 years who had an estimated glomerular filtration rate (eGFR) of greater than 60 ml/min/1.73 m² of body surface area. They were enrolled at 7 sites from February 2000 through June 2009, underwent a 2-4 week washout period during which antihypertensive therapy was discontinued and clonidine and labetalol therapy was maintained, and were randomized to receive either lisinopril plus telmisartan, or lisinopril plus placebo. They were also randomized to a standard blood pressure target of 120/70 to 130/80 mm Hg, or to a low blood pressure target of 95/60 to 110/75 mm Hg. Treatment doses were adjusted to achieve the target blood pressure, said Dr. Chapman of Emory University, Atlanta.

With respect to dual blockade of the renin-angiotensin-aldosterone system (RAAS) and the primary outcome of percentage change in total kidney volume over time, the rate of total kidney volume increase was similar at 6.0% and 6.2% per year in the lisinopril plus telmisartan group and the lisinopril plus placebo group, respectively, according to findings simultaneously published online Nov. 15 in the New England Journal of Medicine, which showed that total kidney volume increased by 40.5% and 42.2% at 60 months in the groups, respectively (N Engl J Med 2014 Nov. 15[doi:10.1056/NEJMoa1402685])

With respect to the standard vs. low blood pressure target, which was the focus of Dr. Chapman’s talk, significant differences were seen in systolic and diastolic blood pressure, with a difference of 13.4 mm Hg and 9.3 mm Hg, respectively, between the groups at the end of the trial, she said.

“Urinary aldosterone levels decreased significantly in both groups. However, there were no differences in the levels of change between the low and standard blood pressure groups,” she said.

The low target group had a 14.2% slower annual increase in total kidney volume at the end of the study as compared with those in the standard blood pressure target group (annualized change of 5.57% in the low target group vs. 6.57% in the standard target group), she said.

Overall, the change in eGFR did not differ between the groups. Urinary albumin excretion and left ventricular mass declined significantly more in the low vs. standard blood pressure control group, and renal vascular resistance remained the same in the low blood pressure control group, but increased in the standard blood pressure control group.

During a mean follow-up of 5 years, no differences were seen between the groups in the rate of hyperkalemia, acute kidney injury, hospitalizations, cardiac-related hospitalizations or mortality, and the event rates were low, she noted.

“Polycystic kidney disease is the fourth leading cause of renal failure in the United States. It is characterized by renal cyst growth with increased total kidney volume, resulting in activation of the renin-angiotensin system, the development of hypertension early, and progression to renal failure. To date there is no evidence that blood pressure control or blockade of the renin-angiotensin-system slows the progression of renal disease,” she said.

This portion of the HALT-PKD trial showed that both dual blockade of the RAAS and rigorous blood pressure control were safe, but that dual blockade provides no benefit as compared with lisinopril monotherapy with regard to change in total kidney volume and eGFR.

Aggressive blood pressure control, however, was of benefit.

“Low blood pressure treatment in young, healthy, hypertensive polycystic kidney disease patients with blockade of the renin-angiotensin-system was well-tolerated and safe and resulted in a 14.2% slower rate of total kidney volume growth over 5 years, reduced left ventricular mass index, urinary albumin secretion, and renal vascular resistance. This is without impact overall on the change in kidney function,” she concluded.

The HALT-PKD trial was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (including a grant to Dr. Chapman), 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. Detailed author disclosures are available with the full text of the HALT-PKD study at NEJM.org.

PHILADELPHIA – Dual blockade of the renin-angiotensin-aldosterone system with combined angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy was no more effective than ACE inhibitor therapy alone for slowing the rate of increase in total kidney volume in patients with early autosomal dominant polycystic kidney disease, investigators have reported.

Notably, though, aggressive blood pressure control, as compared with standard control, was associated with a slower rate of increase in total kidney volume in study A of the Halt Progression of Polycystic Kidney Disease (HALT-PKD) trial, Dr. Arlene B. Chapman reported at Kidney Week 2014.

Participants in the randomized, placebo-controlled 2x2 factorial trial were 423 hypertensive patients aged 15 to 49 years who had an estimated glomerular filtration rate (eGFR) of greater than 60 ml/min/1.73 m² of body surface area. They were enrolled at 7 sites from February 2000 through June 2009, underwent a 2-4 week washout period during which antihypertensive therapy was discontinued and clonidine and labetalol therapy was maintained, and were randomized to receive either lisinopril plus telmisartan, or lisinopril plus placebo. They were also randomized to a standard blood pressure target of 120/70 to 130/80 mm Hg, or to a low blood pressure target of 95/60 to 110/75 mm Hg. Treatment doses were adjusted to achieve the target blood pressure, said Dr. Chapman of Emory University, Atlanta.

With respect to dual blockade of the renin-angiotensin-aldosterone system (RAAS) and the primary outcome of percentage change in total kidney volume over time, the rate of total kidney volume increase was similar at 6.0% and 6.2% per year in the lisinopril plus telmisartan group and the lisinopril plus placebo group, respectively, according to findings simultaneously published online Nov. 15 in the New England Journal of Medicine, which showed that total kidney volume increased by 40.5% and 42.2% at 60 months in the groups, respectively (N Engl J Med 2014 Nov. 15[doi:10.1056/NEJMoa1402685])

With respect to the standard vs. low blood pressure target, which was the focus of Dr. Chapman’s talk, significant differences were seen in systolic and diastolic blood pressure, with a difference of 13.4 mm Hg and 9.3 mm Hg, respectively, between the groups at the end of the trial, she said.

“Urinary aldosterone levels decreased significantly in both groups. However, there were no differences in the levels of change between the low and standard blood pressure groups,” she said.

The low target group had a 14.2% slower annual increase in total kidney volume at the end of the study as compared with those in the standard blood pressure target group (annualized change of 5.57% in the low target group vs. 6.57% in the standard target group), she said.

Overall, the change in eGFR did not differ between the groups. Urinary albumin excretion and left ventricular mass declined significantly more in the low vs. standard blood pressure control group, and renal vascular resistance remained the same in the low blood pressure control group, but increased in the standard blood pressure control group.

During a mean follow-up of 5 years, no differences were seen between the groups in the rate of hyperkalemia, acute kidney injury, hospitalizations, cardiac-related hospitalizations or mortality, and the event rates were low, she noted.

“Polycystic kidney disease is the fourth leading cause of renal failure in the United States. It is characterized by renal cyst growth with increased total kidney volume, resulting in activation of the renin-angiotensin system, the development of hypertension early, and progression to renal failure. To date there is no evidence that blood pressure control or blockade of the renin-angiotensin-system slows the progression of renal disease,” she said.

This portion of the HALT-PKD trial showed that both dual blockade of the RAAS and rigorous blood pressure control were safe, but that dual blockade provides no benefit as compared with lisinopril monotherapy with regard to change in total kidney volume and eGFR.

Aggressive blood pressure control, however, was of benefit.

“Low blood pressure treatment in young, healthy, hypertensive polycystic kidney disease patients with blockade of the renin-angiotensin-system was well-tolerated and safe and resulted in a 14.2% slower rate of total kidney volume growth over 5 years, reduced left ventricular mass index, urinary albumin secretion, and renal vascular resistance. This is without impact overall on the change in kidney function,” she concluded.

The HALT-PKD trial was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (including a grant to Dr. Chapman), 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. Detailed author disclosures are available with the full text of the HALT-PKD study at NEJM.org.