Nebivolol Effect on Nitric Oxide Levels, Blood Pressure, and Renal Function in Kidney Transplant Patients
| Status: | Completed |
|---|---|
| Conditions: | High Blood Pressure (Hypertension) |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/21/2016 |
| Start Date: | July 2010 |
| End Date: | July 2014 |
This study will investigate the blood pressure lowering efficacy of nebivolol among renal
transplant recipients who are on calcineurin inhibitors which are believed to contribute to
hypertension by sympathetic nervous system (SNS) activation and decreased prostaglandin and
nitric oxide production. Hypotheses:
1. There is a significant difference in the effect of 12 months of Nebivolol versus
Metoprolol treatment on the plasma nitric oxide level of hypertensive renal transplant
patients.
2. There is a significant difference in the effect of 12 months of Nebivolol versus
Metoprolol treatment on the estimated glomerular filtration rate of hypertensive renal
transplant patients.
3. There is a significant difference in the effect of 12 months of Nebivolol versus
Metoprolol treatment on the systolic, diastolic and mean arterial blood pressures of
hypertensive renal transplant patients.
transplant recipients who are on calcineurin inhibitors which are believed to contribute to
hypertension by sympathetic nervous system (SNS) activation and decreased prostaglandin and
nitric oxide production. Hypotheses:
1. There is a significant difference in the effect of 12 months of Nebivolol versus
Metoprolol treatment on the plasma nitric oxide level of hypertensive renal transplant
patients.
2. There is a significant difference in the effect of 12 months of Nebivolol versus
Metoprolol treatment on the estimated glomerular filtration rate of hypertensive renal
transplant patients.
3. There is a significant difference in the effect of 12 months of Nebivolol versus
Metoprolol treatment on the systolic, diastolic and mean arterial blood pressures of
hypertensive renal transplant patients.
Nitric Oxide (NO) plays a plethora of functions in the kidney including vascular and
hemodynamic regulation, fluid and electrolyte transport, and is an important component of
pressure natriuresis and tubule-glomerular feedback.
Deficient NO levels have been associated with oxidative stress in conditions like
hypertension, diabetes mellitus, and cardiovascular disease. NO deficiency has been
identified in states of chronic progressive renal disease and altered NO production and/or
decreased bioavailability is believed to characterize the endothelial dysfunction and
resistant hypertension of renal failure.
It has been shown that kidney transplantation improves endothelium-dependent vasodilation in
patients with end-stage renal disease (ESRD) and the NO activity significantly increases
after transplantation. However, calcineurin inhibitor drugs used in the anti-rejection
regimen can reduce endothelial NO production and aggravate hypertension through vascular and
renal mechanisms. In turn, uncontrolled elevation in blood pressure has been associated with
increased renal allograft failure and post-transplant mortality.
In the absence of randomized clinical trials of antihypertensive drugs and optimal blood
pressure goals in kidney transplant recipients. There is no scientifically-robust consensus
on the specific drugs to use among transplant patients. Nebivolol, is a third generation
B1-selective B-blocker shown to have similar BP-lowering effect as other B-blockers,
angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blocker (ARB)
drugs, and calcium channel blockers. Nebivolol ameliorates hypertension by increasing NO
release, promoting arterial and venous vasodilatation and beta-blockade. Nebivolol has
beneficial effect on the kidney allograft. Studies in animal transplants have shown that
nebivolol could reduce ischemia-induced reperfusion injury, alleviate renal perfusion
pressure and increase NO release with associated vasodilation of the renal vasculature.
These effects have not been seen with older generation B-blockers like propranolol or
bisoprolol. Finally, in surgically reduced renal mass, nebivolol has been demonstrated to
attenuate collagen type 1 expression with lessening of glomerular and interstitial fibrosis.
In this study, the effect of nebivolol and metoprolol on the change in NO level at baseline
and at the 12th month of treatment will be compared. Similarly,the effects of the two drugs
on the change in renal function, blood pressure, and blood pressure regimen from baseline to
month-12 of treatment will also be compared.
hemodynamic regulation, fluid and electrolyte transport, and is an important component of
pressure natriuresis and tubule-glomerular feedback.
Deficient NO levels have been associated with oxidative stress in conditions like
hypertension, diabetes mellitus, and cardiovascular disease. NO deficiency has been
identified in states of chronic progressive renal disease and altered NO production and/or
decreased bioavailability is believed to characterize the endothelial dysfunction and
resistant hypertension of renal failure.
It has been shown that kidney transplantation improves endothelium-dependent vasodilation in
patients with end-stage renal disease (ESRD) and the NO activity significantly increases
after transplantation. However, calcineurin inhibitor drugs used in the anti-rejection
regimen can reduce endothelial NO production and aggravate hypertension through vascular and
renal mechanisms. In turn, uncontrolled elevation in blood pressure has been associated with
increased renal allograft failure and post-transplant mortality.
In the absence of randomized clinical trials of antihypertensive drugs and optimal blood
pressure goals in kidney transplant recipients. There is no scientifically-robust consensus
on the specific drugs to use among transplant patients. Nebivolol, is a third generation
B1-selective B-blocker shown to have similar BP-lowering effect as other B-blockers,
angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blocker (ARB)
drugs, and calcium channel blockers. Nebivolol ameliorates hypertension by increasing NO
release, promoting arterial and venous vasodilatation and beta-blockade. Nebivolol has
beneficial effect on the kidney allograft. Studies in animal transplants have shown that
nebivolol could reduce ischemia-induced reperfusion injury, alleviate renal perfusion
pressure and increase NO release with associated vasodilation of the renal vasculature.
These effects have not been seen with older generation B-blockers like propranolol or
bisoprolol. Finally, in surgically reduced renal mass, nebivolol has been demonstrated to
attenuate collagen type 1 expression with lessening of glomerular and interstitial fibrosis.
In this study, the effect of nebivolol and metoprolol on the change in NO level at baseline
and at the 12th month of treatment will be compared. Similarly,the effects of the two drugs
on the change in renal function, blood pressure, and blood pressure regimen from baseline to
month-12 of treatment will also be compared.
Inclusion Criteria:
- Men or women at least 18 years of age who are recipients of - a solitary kidney or
combined kidney-pancreas transplant within the last twenty four months
- Current diagnosis of hypertension
- Normal hepatic enzymes
- Estimated creatinine clearance (by cockcroft-gault formula) >or= 30 ml/min
Exclusion Criteria:
- Any contraindication to taking beta-blockers, specifically Nebivolol or Metoprolol.
Conditions such as : (bradycardia heart rate (HR) <60 beats per minute , heart block
> 1st degree, decompensated cardiac failure, sick sinus syndrome (unless permanent
pacemaker in place), severe hepatic impairment( defined as elevation of aspartamine
aminotransferase , alanine aminotransferase, or bilirubin levels to three times upper
limit of normal reference range), severe peripheral arterial circulatory disorder,
history of bronchospasm and /or asthma and /or regular medication with inhaled
bronchodilators. or , or any medical condition that in the opinion of the
investigator may interfere with the subject's ability to successfully complete the
protocol.
- Any medical condition which, in the opinion of the Principal Investigator, might
compromise the safety of the subject in participating in the protocol such as
hypotension or not requiring antihypertensive medications.
- Any serious systemic disease that might complicate management and reduce life
expectancy.
- Uncontrolled hypertension defined as systolic blood pressure (SBP) > 210 or diastolic
blood pressure (DBP) > 120 mm Hg.
- Symptomatic hypotension
- Previous intolerance to beta blockers
- Cerebrovascular accident within 3 months of randomization
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