Angiotensin blockade in late autosomal dominant polycystic kidney disease

Vicente Torres, Kaleab Z. Abebe, Arlene B. Chapman, Robert W. Schrier, 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, Charity G. Moore, Ronald D. Perrone

Research output: Contribution to journalArticle

133 Citations (Scopus)

Abstract

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 m2 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.

Original languageEnglish (US)
Pages (from-to)2267-2276
Number of pages10
JournalNew England Journal of Medicine
Volume371
Issue number24
DOIs
StatePublished - Dec 11 2014

Fingerprint

Autosomal Dominant Polycystic Kidney
Angiotensins
Lisinopril
Glomerular Filtration Rate
Angiotensin Receptor Antagonists
Angiotensin-Converting Enzyme Inhibitors
Renin-Angiotensin System
Blood Pressure
Aldosterone
Albumins
Placebos
Hypertension
Hyperkalemia
Body Surface Area
Incidence
Chronic Renal Insufficiency
Acute Kidney Injury
Chronic Kidney Failure
Disease Progression
Hospitalization

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Torres, V., Abebe, K. Z., Chapman, A. B., Schrier, R. W., Braun, W. E., Steinman, T. I., ... Perrone, R. D. (2014). Angiotensin blockade in late autosomal dominant polycystic kidney disease. New England Journal of Medicine, 371(24), 2267-2276. https://doi.org/10.1056/NEJMoa1402686

Angiotensin blockade in late autosomal dominant polycystic kidney disease. / Torres, Vicente; Abebe, Kaleab Z.; Chapman, Arlene B.; Schrier, Robert W.; Braun, William E.; Steinman, Theodore I.; Winklhofer, Franz T.; Brosnahan, Godela; Czarnecki, Peter G.; Hogan, Marie C; Miskulin, Dana C.; Rahbari-Oskoui, Frederic F.; Grantham, Jared J.; Harris, Peter C; Flessner, Michael F.; Moore, Charity G.; Perrone, Ronald D.

In: New England Journal of Medicine, Vol. 371, No. 24, 11.12.2014, p. 2267-2276.

Research output: Contribution to journalArticle

Torres, V, Abebe, KZ, Chapman, AB, Schrier, RW, Braun, WE, Steinman, TI, Winklhofer, FT, Brosnahan, G, Czarnecki, PG, Hogan, MC, Miskulin, DC, Rahbari-Oskoui, FF, Grantham, JJ, Harris, PC, Flessner, MF, Moore, CG & Perrone, RD 2014, 'Angiotensin blockade in late autosomal dominant polycystic kidney disease', New England Journal of Medicine, vol. 371, no. 24, pp. 2267-2276. https://doi.org/10.1056/NEJMoa1402686
Torres V, Abebe KZ, Chapman AB, Schrier RW, Braun WE, Steinman TI et al. Angiotensin blockade in late autosomal dominant polycystic kidney disease. New England Journal of Medicine. 2014 Dec 11;371(24):2267-2276. https://doi.org/10.1056/NEJMoa1402686
Torres, Vicente ; Abebe, Kaleab Z. ; Chapman, Arlene B. ; Schrier, Robert W. ; Braun, William E. ; Steinman, Theodore I. ; Winklhofer, Franz T. ; Brosnahan, Godela ; Czarnecki, Peter G. ; Hogan, Marie C ; Miskulin, Dana C. ; Rahbari-Oskoui, Frederic F. ; Grantham, Jared J. ; Harris, Peter C ; Flessner, Michael F. ; Moore, Charity G. ; Perrone, Ronald D. / Angiotensin blockade in late autosomal dominant polycystic kidney disease. In: New England Journal of Medicine. 2014 ; Vol. 371, No. 24. pp. 2267-2276.
@article{18bd7813090745edb44b22cb1e1c8eb6,
title = "Angiotensin blockade in late autosomal dominant polycystic kidney disease",
abstract = "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 m2 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.",
author = "Vicente Torres and Abebe, {Kaleab Z.} and Chapman, {Arlene B.} and Schrier, {Robert W.} and Braun, {William E.} and Steinman, {Theodore I.} and Winklhofer, {Franz T.} and Godela Brosnahan and Czarnecki, {Peter G.} and Hogan, {Marie C} and Miskulin, {Dana C.} and Rahbari-Oskoui, {Frederic F.} and Grantham, {Jared J.} and Harris, {Peter C} and Flessner, {Michael F.} and Moore, {Charity G.} and Perrone, {Ronald D.}",
year = "2014",
month = "12",
day = "11",
doi = "10.1056/NEJMoa1402686",
language = "English (US)",
volume = "371",
pages = "2267--2276",
journal = "New England Journal of Medicine",
issn = "1533-4406",
publisher = "Massachussetts Medical Society",
number = "24",

}

TY - JOUR

T1 - Angiotensin blockade in late autosomal dominant polycystic kidney disease

AU - Torres, Vicente

AU - Abebe, Kaleab Z.

AU - Chapman, Arlene B.

AU - Schrier, Robert W.

AU - Braun, William E.

AU - Steinman, Theodore I.

AU - Winklhofer, Franz T.

AU - Brosnahan, Godela

AU - Czarnecki, Peter G.

AU - Hogan, Marie C

AU - Miskulin, Dana C.

AU - Rahbari-Oskoui, Frederic F.

AU - Grantham, Jared J.

AU - Harris, Peter C

AU - Flessner, Michael F.

AU - Moore, Charity G.

AU - Perrone, Ronald D.

PY - 2014/12/11

Y1 - 2014/12/11

N2 - 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 m2 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.

AB - 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 m2 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.

UR - http://www.scopus.com/inward/record.url?scp=84918564157&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84918564157&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa1402686

DO - 10.1056/NEJMoa1402686

M3 - Article

C2 - 25399731

AN - SCOPUS:84918564157

VL - 371

SP - 2267

EP - 2276

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 1533-4406

IS - 24

ER -