Add-on and withdrawal effect of pravastatin on proteinuria in hypertensive patients treated with AT receptor blockers
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.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2005 |
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| Erschienen: |
2005 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:68 |
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| Enthalten in: |
Kidney international - 68(2005), 2 vom: 01. Aug., Seite 779-87 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lee, Tsung-Ming [VerfasserIn] |
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| Anmerkungen: |
Date Completed 13.10.2005 Date Revised 21.11.2013 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM156511185 |
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| 041 | |a eng | ||
| 100 | 1 | |a Lee, Tsung-Ming |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Add-on and withdrawal effect of pravastatin on proteinuria in hypertensive patients treated with AT receptor blockers |
| 264 | 1 | |c 2005 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 13.10.2005 | ||
| 500 | |a Date Revised 21.11.2013 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Clinical Trial | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Angiotensin II Type 1 Receptor Blockers |2 NLM | |
| 650 | 7 | |a Endothelin-1 |2 NLM | |
| 650 | 7 | |a Hydroxymethylglutaryl-CoA Reductase Inhibitors |2 NLM | |
| 650 | 7 | |a Lipids |2 NLM | |
| 650 | 7 | |a Losartan |2 NLM | |
| 650 | 7 | |a JMS50MPO89 |2 NLM | |
| 650 | 7 | |a Pravastatin |2 NLM | |
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| 700 | 1 | |a Lin, Mei-Shu |e verfasserin |4 aut | |
| 700 | 1 | |a Tsai, Chang-Her |e verfasserin |4 aut | |
| 700 | 1 | |a Chang, Nen-Chung |e verfasserin |4 aut | |
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