Angiotensin blockade in late autosomal dominant polycystic kidney disease.
BACKGROUND
Hypertension develops early in patients with autosomal dominant polycystic kidney disease (ADPKD) and is associated with disease progression. The renin-angiotensin-aldosterone system (RAAS) is implicated in the pathogenesis of hypertension in patients with ADPKD. Dual blockade of the RAAS may circumvent compensatory mechanisms that limit the efficacy of monotherapy with an angiotensin-converting-enzyme (ACE) inhibitor or angiotensin II-receptor blocker (ARB).


METHODS
In this double-blind, placebo-controlled trial, we randomly assigned 486 patients, 18 to 64 years of age, with ADPKD (estimated glomerular filtration rate [GFR], 25 to 60 ml per minute per 1.73 m(2) of body-surface area) to receive an ACE inhibitor (lisinopril) and placebo or lisinopril and an ARB (telmisartan), with the doses adjusted to achieve a blood pressure of 110/70 to 130/80 mm Hg. The composite primary outcome was the time to death, end-stage renal disease, or a 50% reduction from the baseline estimated GFR. Secondary outcomes included the rates of change in urinary aldosterone and albumin excretion, frequency of hospitalizations for any cause and for cardiovascular causes, incidence of pain, frequency of ADPKD-related symptoms, quality of life, and adverse study-medication effects. Patients were followed for 5 to 8 years.


RESULTS
There was no significant difference between the study groups in the incidence of the composite primary outcome (hazard ratio with lisinopril-telmisartan, 1.08; 95% confidence interval, 0.82 to 1.42). The two treatments controlled blood pressure and lowered urinary aldosterone excretion similarly. The rates of decline in the estimated GFR, urinary albumin excretion, and other secondary outcomes and adverse events, including hyperkalemia and acute kidney injury, were also similar in the two groups.


CONCLUSIONS
Monotherapy with an ACE inhibitor was associated with blood-pressure control in most patients with ADPKD and stage 3 chronic kidney disease. The addition of an ARB did not alter the decline in the estimated GFR. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; HALT-PKD [Study B] ClinicalTrials.gov number, NCT01885559.).
From the Mayo Clinic College of Medicine, Rochester, MN (V.E.T., M.C.H., P.C.H.); University of Pittsburgh School of Medicine, Pittsburgh (K.Z.A., C.G.M.); Emory University School of Medicine, Atlanta (A.B.C., F.F.R.-O.); University of Colorado Health Sciences Center, Denver (R.W.S., G.B.); Cleveland Clinic, Cleveland (W.E.B.); Beth Israel Deaconess Medical Center (T.I.S., P.G.C.) and Tufts Medical Center (D.C.M., R.D.P.) - both in Boston; Kansas University Medical Center, Kansas City (F.T.W., J.J.G.) and the National Institutes of Health, Bethesda, MD (M.F.F.).
Vicente E
VE
Torres
Kaleab Z
KZ
Abebe
Arlene B
AB
Chapman
Robert W
RW
Schrier
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
Charity G
CG
Moore
Ronald D
RD
Perrone
D000293:Adolescent; D000328:Adult; D000419:Albuminuria / Q000209:etiology; D000450:Aldosterone / Q000652:urine; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / 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 / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology; D007676:Kidney Failure, Chronic / Q000517:prevention & control; D017706:Lisinopril / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016891:Polycystic Kidney, Autosomal Dominant / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy / Q000209:etiology; D000077333:Telmisartan; D055815:Young Adult
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001565:Benzoates; D000450:Aldosterone; D017706:Lisinopril; D000077333:Telmisartan