Add-on and withdrawal effect of pravastatin on proteinuria in hypertensive patients treated with AT1 receptor blockers

Tsung-Ming Lee, Mei Shu Lin, Chang Her Tsai, Nen Chung Chang

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Background. Although angiotensin receptor antagonists and 3-hydroxy-3-methylgultaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have been shown to attenuate proteinuria individually, it remains unclear whether proteinuria may be additionally improved by statin therapy in well-controlled hypertensive patients treated with angiotensin receptor antagonists-based regimen and whether withdrawal of chronic statin treatment may abrogate this beneficial effect in normolipidemic patients. Methods. A total of consecutive 82 proteinuric patients treated with antihypertensive agents, including losartan, were randomized 10 mg of pravastatin or placebo with a 6-month treatment. After completing 6 months of drug treatment, the pravastatin-treated patients were randomly assigned to continue (N = 19) or withdraw (N = 17) pravastatin for a further 6 months. Results. Subjects treated with pravastatin had significant further improvement of proteinuria at 6 months compared with placebo group (559 ± 251 mg/24 hours vs. 1262 ± 557 mg/24 hours) (P <0.0001). Of 17 patients assigned to withdraw pravastatin, proteinuria returned to the pretreatment levels and was significantly higher than those who continued treatment. Multivariate analysis revealed that proteinuric improvement was significantly correlated with the continuous statin use. Urinary excretion of endothelin-1 (ET-1) is decreased in pravastatin-treated patients, but withdrawal of statin resulted in 27% up-regulation. The linear regression models in the initial statin-treated group showed that changes in urinary ET-1 correlated with urinary protein excretion (r = 0.83, P <0.0001). Conclusion. We conclude that pravastatin administration is associated with improved proteinuria probably by inhibiting urine ET-1 levels in patients with losartan-based treatment. However, statin withdrawal abrogates this beneficial effect in patients initially responsive to this therapy.

Original languageEnglish
Pages (from-to)779-787
Number of pages9
JournalKidney International
Volume68
Issue number2
DOIs
Publication statusPublished - Aug 2005

Fingerprint

Pravastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Proteinuria
Endothelin-1
Losartan
Angiotensin Receptor Antagonists
Therapeutics
Linear Models
Placebos
Coenzyme A
Antihypertensive Agents
Oxidoreductases
Up-Regulation
Multivariate Analysis
Urine

Keywords

  • Angiotensin II receptor blockers
  • Endothelin-1
  • Hypertension
  • Pravastatin
  • Proteinuria

ASJC Scopus subject areas

  • Nephrology

Cite this

Add-on and withdrawal effect of pravastatin on proteinuria in hypertensive patients treated with AT1 receptor blockers. / Lee, Tsung-Ming; Lin, Mei Shu; Tsai, Chang Her; Chang, Nen Chung.

In: Kidney International, Vol. 68, No. 2, 08.2005, p. 779-787.

Research output: Contribution to journalArticle

@article{21435ca2df6445b5842d897d0f200930,
title = "Add-on and withdrawal effect of pravastatin on proteinuria in hypertensive patients treated with AT1 receptor blockers",
abstract = "Background. Although angiotensin receptor antagonists and 3-hydroxy-3-methylgultaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have been shown to attenuate proteinuria individually, it remains unclear whether proteinuria may be additionally improved by statin therapy in well-controlled hypertensive patients treated with angiotensin receptor antagonists-based regimen and whether withdrawal of chronic statin treatment may abrogate this beneficial effect in normolipidemic patients. Methods. A total of consecutive 82 proteinuric patients treated with antihypertensive agents, including losartan, were randomized 10 mg of pravastatin or placebo with a 6-month treatment. After completing 6 months of drug treatment, the pravastatin-treated patients were randomly assigned to continue (N = 19) or withdraw (N = 17) pravastatin for a further 6 months. Results. Subjects treated with pravastatin had significant further improvement of proteinuria at 6 months compared with placebo group (559 ± 251 mg/24 hours vs. 1262 ± 557 mg/24 hours) (P <0.0001). Of 17 patients assigned to withdraw pravastatin, proteinuria returned to the pretreatment levels and was significantly higher than those who continued treatment. Multivariate analysis revealed that proteinuric improvement was significantly correlated with the continuous statin use. Urinary excretion of endothelin-1 (ET-1) is decreased in pravastatin-treated patients, but withdrawal of statin resulted in 27{\%} up-regulation. The linear regression models in the initial statin-treated group showed that changes in urinary ET-1 correlated with urinary protein excretion (r = 0.83, P <0.0001). Conclusion. We conclude that pravastatin administration is associated with improved proteinuria probably by inhibiting urine ET-1 levels in patients with losartan-based treatment. However, statin withdrawal abrogates this beneficial effect in patients initially responsive to this therapy.",
keywords = "Angiotensin II receptor blockers, Endothelin-1, Hypertension, Pravastatin, Proteinuria",
author = "Tsung-Ming Lee and Lin, {Mei Shu} and Tsai, {Chang Her} and Chang, {Nen Chung}",
year = "2005",
month = "8",
doi = "10.1111/j.1523-1755.2005.00457.x",
language = "English",
volume = "68",
pages = "779--787",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "2",

}

TY - JOUR

T1 - Add-on and withdrawal effect of pravastatin on proteinuria in hypertensive patients treated with AT1 receptor blockers

AU - Lee, Tsung-Ming

AU - Lin, Mei Shu

AU - Tsai, Chang Her

AU - Chang, Nen Chung

PY - 2005/8

Y1 - 2005/8

N2 - Background. Although angiotensin receptor antagonists and 3-hydroxy-3-methylgultaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have been shown to attenuate proteinuria individually, it remains unclear whether proteinuria may be additionally improved by statin therapy in well-controlled hypertensive patients treated with angiotensin receptor antagonists-based regimen and whether withdrawal of chronic statin treatment may abrogate this beneficial effect in normolipidemic patients. Methods. A total of consecutive 82 proteinuric patients treated with antihypertensive agents, including losartan, were randomized 10 mg of pravastatin or placebo with a 6-month treatment. After completing 6 months of drug treatment, the pravastatin-treated patients were randomly assigned to continue (N = 19) or withdraw (N = 17) pravastatin for a further 6 months. Results. Subjects treated with pravastatin had significant further improvement of proteinuria at 6 months compared with placebo group (559 ± 251 mg/24 hours vs. 1262 ± 557 mg/24 hours) (P <0.0001). Of 17 patients assigned to withdraw pravastatin, proteinuria returned to the pretreatment levels and was significantly higher than those who continued treatment. Multivariate analysis revealed that proteinuric improvement was significantly correlated with the continuous statin use. Urinary excretion of endothelin-1 (ET-1) is decreased in pravastatin-treated patients, but withdrawal of statin resulted in 27% up-regulation. The linear regression models in the initial statin-treated group showed that changes in urinary ET-1 correlated with urinary protein excretion (r = 0.83, P <0.0001). Conclusion. We conclude that pravastatin administration is associated with improved proteinuria probably by inhibiting urine ET-1 levels in patients with losartan-based treatment. However, statin withdrawal abrogates this beneficial effect in patients initially responsive to this therapy.

AB - Background. Although angiotensin receptor antagonists and 3-hydroxy-3-methylgultaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have been shown to attenuate proteinuria individually, it remains unclear whether proteinuria may be additionally improved by statin therapy in well-controlled hypertensive patients treated with angiotensin receptor antagonists-based regimen and whether withdrawal of chronic statin treatment may abrogate this beneficial effect in normolipidemic patients. Methods. A total of consecutive 82 proteinuric patients treated with antihypertensive agents, including losartan, were randomized 10 mg of pravastatin or placebo with a 6-month treatment. After completing 6 months of drug treatment, the pravastatin-treated patients were randomly assigned to continue (N = 19) or withdraw (N = 17) pravastatin for a further 6 months. Results. Subjects treated with pravastatin had significant further improvement of proteinuria at 6 months compared with placebo group (559 ± 251 mg/24 hours vs. 1262 ± 557 mg/24 hours) (P <0.0001). Of 17 patients assigned to withdraw pravastatin, proteinuria returned to the pretreatment levels and was significantly higher than those who continued treatment. Multivariate analysis revealed that proteinuric improvement was significantly correlated with the continuous statin use. Urinary excretion of endothelin-1 (ET-1) is decreased in pravastatin-treated patients, but withdrawal of statin resulted in 27% up-regulation. The linear regression models in the initial statin-treated group showed that changes in urinary ET-1 correlated with urinary protein excretion (r = 0.83, P <0.0001). Conclusion. We conclude that pravastatin administration is associated with improved proteinuria probably by inhibiting urine ET-1 levels in patients with losartan-based treatment. However, statin withdrawal abrogates this beneficial effect in patients initially responsive to this therapy.

KW - Angiotensin II receptor blockers

KW - Endothelin-1

KW - Hypertension

KW - Pravastatin

KW - Proteinuria

UR - http://www.scopus.com/inward/record.url?scp=26944458167&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=26944458167&partnerID=8YFLogxK

U2 - 10.1111/j.1523-1755.2005.00457.x

DO - 10.1111/j.1523-1755.2005.00457.x

M3 - Article

C2 - 16014056

AN - SCOPUS:26944458167

VL - 68

SP - 779

EP - 787

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 2

ER -