Blood pressure in early autosomal dominant polycystic kidney disease

N Engl J Med. 2014 Dec 11;371(24):2255-66. doi: 10.1056/NEJMoa1402685. Epub 2014 Nov 15.

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.).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*
  • Hypertension / etiology
  • Kidney / pathology*
  • Lisinopril / therapeutic use*
  • Male
  • Middle Aged
  • Organ Size / drug effects
  • Polycystic Kidney, Autosomal Dominant / drug therapy*
  • Polycystic Kidney, Autosomal Dominant / pathology
  • Polycystic Kidney, Autosomal Dominant / physiopathology
  • Telmisartan
  • Young Adult

Substances

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

Associated data

  • ClinicalTrials.gov/NCT00283686

Grant support