Blood pressure in early autosomal dominant polycystic kidney disease.

Abstract

BACKGROUND:

Hypertension is common in autosomal dominant polycystic kidney disease (ADPKD) and is associated with increased total kidney volume, activation of the renin-angiotensin-aldosterone system, and progression of kidney disease.

METHODS:

In this double-blind, placebo-controlled trial, we randomly assigned 558 hypertensive participants with ADPKD (15 to 49 years of age, with an estimated glomerular filtration rate [GFR] >60 ml per minute per 1.73 m(2) of body-surface area) to either a standard blood-pressure target (120/70 to 130/80 mm Hg) or a low blood-pressure target (95/60 to 110/75 mm Hg) and to either an angiotensin-converting-enzyme inhibitor (lisinopril) plus an angiotensin-receptor blocker (telmisartan) or lisinopril plus placebo. The primary outcome was the annual percentage change in the total kidney volume.

RESULTS:

The annual percentage increase in total kidney volume was significantly lower in the low-blood-pressure group than in the standard-blood-pressure group (5.6% vs. 6.6%, P=0.006), without significant differences between the lisinopril-telmisartan group and the lisinopril-placebo group. The rate of change in estimated GFR was similar in the two medication groups, with a negative slope difference in the short term in the low-blood-pressure group as compared with the standard-blood-pressure group (P<0.001) and a marginally positive slope difference in the long term (P=0.05). The left-ventricular-mass index decreased more in the low-blood-pressure group than in the standard-blood-pressure group (-1.17 vs. -0.57 g per square meter per year, P<0.001); urinary albumin excretion was reduced by 3.77% with the low-pressure target and increased by 2.43% with the standard target (P<0.001). Dizziness and light-headedness were more common in the low-blood-pressure group than in the standard-blood-pressure group (80.7% vs. 69.4%, P=0.002).

CONCLUSIONS:

In early ADPKD, the combination of lisinopril and telmisartan did not significantly alter the rate of increase in total kidney volume. As compared with standard blood-pressure control, rigorous blood-pressure control was associated with a slower increase in total kidney volume, no overall change in the estimated GFR, a greater decline in the left-ventricular-mass index, and greater reduction in urinary albumin excretion. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; HALT-PKD [Study A] ClinicalTrials.gov number, NCT00283686.).

• Authors: Robert W Schrier, Kaleab Z Abebe, Ronald D Perrone, Vicente E Torres, William E Braun, Theodore I Steinman, Franz T Winklhofer, Godela Brosnahan, Peter G Czarnecki, Marie C Hogan, Dana C Miskulin, Frederic F Rahbari-Oskoui, Jared J Grantham, Peter C Harris, Michael F Flessner, Kyongtae T Bae, Charity G Moore, Arlene B Chapman, HALT-PKD Trial Investigators
• Journal: The New England journal of medicine (N Engl J Med) Vol. 371 Issue 24 Pg. 2255-66 (Dec 11 2014) ISSN: 1533-4406 [Electronic] United States
• PMID: 25399733 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Angiotensin-Converting Enzyme Inhibitors
• Antihypertensive Agents
• Benzimidazoles
• Benzoates
• Lisinopril
• Telmisartan

Topics

• Adolescent
• Adult
• Angiotensin II Type 1 Receptor Blockers (therapeutic use)
• Angiotensin-Converting Enzyme Inhibitors (therapeutic use)
• Antihypertensive Agents (therapeutic use)
• Benzimidazoles (therapeutic use)
• Benzoates (therapeutic use)
• Blood Pressure (drug effects)
• Disease Progression
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Glomerular Filtration Rate
• Humans
• Hypertension (drug therapy, etiology)
• Kidney (pathology)
• Lisinopril (therapeutic use)
• Male
• Middle Aged
• Organ Size (drug effects)
• Polycystic Kidney, Autosomal Dominant (drug therapy, pathology, physiopathology)
• Telmisartan
• Young Adult