Clinical Nephrology – Epidemiology – Clinical Trials
Kidney International (2005) 68, 779–787; doi:10.1111/j.1523-1755.2005.00457.x
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 and NEN-CHUNG CHANG
Cardiology Section, Department of Internal Medicine, Taipei Medical University and Chi-Mei Medical Center, Tainan, Taiwan; National Taiwan University and Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan; Cardiology Section, Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan; Cardiology Section, Department of Medicine, Taipei Medical University and Hospital, Taipei, Taiwan
Correspondence: Dr Nen-Chung Chang, Cardiology Section, Department of Medicine, Taipei Medical University and Hospital 252, Wu-Hsing St., Taipei, Taiwan. E-Mail: ncchang@mu.edu.tw
Received 6 September 2004; Revised 16 January 2005; Re-revised 18 February 2005; Accepted 15 March 2005.
Abstract
Add-on and withdrawal effect of pravastatin on proteinuria in hypertensive patients treated with AT1 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.
Keywords:
angiotensin II receptor blockers, endothelin-1, hypertension, pravastatin, proteinuria
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