Blood pressure in early autosomal dominant polycystic kidney disease.
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.).
From the University of Colorado, Denver (R.W.S., G.B.); University of Pittsburgh School of Medicine, Pittsburgh (K.Z.A., K.T.B., C.G.M.); Tufts Medical Center (R.D.P., D.C.M.) and Beth Israel Deaconess Medical Center (T.I.S., P.G.C.) - both in Boston; Mayo Clinic College of Medicine, Rochester, MN (V.E.T., M.C.H., P.C.H.); Cleveland Clinic, Cleveland (W.E.B.); Kansas University Medical Center, Kansas City (F.T.W., J.J.G.); Emory University School of Medicine, Atlanta (F.F.R.-O., A.B.C.); and the National Institutes of Health, Bethesda, MD (M.F.F.).
Robert W
RW
Schrier
Kaleab Z
KZ
Abebe
Ronald D
RD
Perrone
Vicente E
VE
Torres
William E
WE
Braun
Theodore I
TI
Steinman
Franz T
FT
Winklhofer
Godela
G
Brosnahan
Peter G
PG
Czarnecki
Marie C
MC
Hogan
Dana C
DC
Miskulin
Frederic F
FF
Rahbari-Oskoui
Jared J
JJ
Grantham
Peter C
PC
Harris
Michael F
MF
Flessner
Kyongtae T
KT
Bae
Charity G
CG
Moore
Arlene B
AB
Chapman
D000293:Adolescent; D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001565:Benzoates / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology; D007668:Kidney / Q000473:pathology*; D017706:Lisinopril / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009929:Organ Size / Q000187:drug effects; D016891:Polycystic Kidney, Autosomal Dominant / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D000077333:Telmisartan; D055815:Young Adult
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001565:Benzoates; D017706:Lisinopril; D000077333:Telmisartan