Renal Protective Effects of Renin Angiotensin System (RAS) Inhibitor in Peritoneal Dialysis Patients

Study Overview
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Brief Summary
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This is a multicentre study examining the effectiveness of angiotension converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB) or a combination of both in reducing the rate of decline in residual renal function (RRF) in continuous ambulatory peritoneal dialysis (CAPD) patients.

Detailed Description
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RRF has been shown to decline progressively with time on dialysis in both CAPD and hemodialysis. Although RRF is an important determinant of mortality and morbidity in peritoneal dialysis (PD) patients, few studies have addressed therapeutic approaches for preserving RRF after the initiation of dialysis therapy. Blockade of the renin-angiotensin system by ACEI or ARB is a well-established approach for renoprotection in pre-dialysis chronic kidney disease patients. Up to now, only two trials showed that an ACEI, ramipril, and ARB, valsartan , were effective in the preservation of RRF of CAPD patients. However it is important to point out that the evidence cited has limitations. First, the trial only involved patients from one university teaching hospital. Second, transport characteristics, were not assessed before the start of the study. Third, the trial was too small to detect potentially important differences in health care use and survival between groups. Therefore, whether both ACEI and ARB preserve RRF, improve clinical outcomes and decrease health care use and costs should be tested in much longer and larger studies involving multiple sites. In order to confirm these findings, here the investigators will perform prospective, randomized, open-label and multiple center study to address long-term effects of ACEI, ARB and combination of both therapy on RRF in Patients on CAPD.

Official Title
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Effects of Benazepril,Valsartan or Combination of Both on Residual Renal Function in Peritoneal Dialysis Patients

Conditions
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Renal Function Disorder

Intervention / Treatment
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* Drug: Benazepril
* Drug: Valsartan
* Drug: Benazepril+Valsartan
* Drug: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients received CAPD more than 1 months Subjects of either sex, 20-75 years old Residual GFR of 3mL/min per 1.73 m2 or more With hypertension No history of taking an ACE inhibitor or angiotensin-receptor blockers for at least 1 month Provision of written informed consent by subject or guardian Exclusion Criteria: Underlying medical conditions, such as congestive heart failure, or therapy with an ACE inhibitor or ARB Peritonitis or volume overload within the preceding 1 month Myocardial infarction within the preceding 6 months Clinically significant valvular disease Malignant hypertension History of hypertensive encephalopathy or cerebrovascular accident within the preceding 6 months Any condition that may have precluded a patient from remaining in the study, such as alcohol or drug abuse, chronic liver disease, malignant disease, or psychiatric disorder History of allergy or intolerance to an ACE inhibitor or ARB Participation in another clinic trial within 2 weeks prior to screening

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ACE inhibitor, benazepril<br>Benazepril will be started at 10 mg/day and will be up-titrated to 20 mg/day according to BP control and tolerability. | Drug: Benazepril<br>* Patients with hypertension will take 10-20mg benazepril per day, antihypertensive agents other than ACE inhibitors and ARBs will be allowed. Doses are adjusted appropriately to achieve and maintain the target blood pressure of 120-140/70-90 mmHg.<br>* Other names: Benazepril group;|
| Experimental: Angiotensin receptor blocker, valsartan<br>Valsartan will be started at 80 mg/day and will be up-titrated to 160 mg/day according to BP control and tolerability. | Drug: Valsartan<br>* Patients with hypertension will take 80-160mg valsartan per day, antihypertensive agents other than ACE inhibitors and ARBs will be allowed. Doses are adjusted appropriately to achieve and maintain the target blood pressure of 120-140/70-90 mmHg.<br>* Other names: Valsartan group;|
| Experimental: RAS inhibitors, benazepril+valsartan<br>Benazepril will be started at 10 mg/day and will be up-titrated to 20 mg/day, and valsartan will be started at 80 mg/day and will be up-titrated to 160 mg/day according to BP control and tolerability. | Drug: Benazepril+Valsartan<br>* Patients with hypertension will take 10-20mg benazepril plus 80-160mg valsartan per day, antihypertensive agents other than ACE inhibitors and ARBs will be allowed. Doses are adjusted appropriately to achieve and maintain the target blood pressure of 120-140/70-90 mmHg.<br>* Other names: Benazepril plus Valsartan group;|
| Active Comparator: non-RAS inhibitors, control<br>Drug: antihypertensive agents, except ACE inhibitors and ARBs. Administration of antihypertensive agents will select as follows: CCB→β-blocker→α-blocker. | Drug: Control<br>* Patients in the control group will administer antihypertensive agents, except ACE inhibitors and ARBs. Doses are adjusted appropriately to achieve and maintain the target blood pressure of 120-140/70-90 mmHg.<br>* Other names: Control group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The longitudinal change in residual glomerular filtration rate (GFR) | Residual GFR is defined as the average of 24-hour urinary urea and creatinine clearances. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dialysis adequacy | Indices of the adequacy of dialysis include Kt/V and weekly creatinine clearance assessed by 24-hour dialysate and urinary collection. | 3 years | 
| Peritoneal membrane function | Peritoneal membrane function assessed by standard peritoneal equilibration test. | 3 years | 
| Blood pressure | Office systolic and diastolic blood pressure measurement during follow up period. | 3 years | 
| The time to anuria | Anuria is defined as urine volume < 100ml/d. | 3 years | 
| Number of participants not alive | Death from any cause. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Continuous Ambulatory Peritoneal Dialysis, Angiotensin-converting Enzyme Inhibitor, Angiotensin II Receptor Blocker, Renin angiotensin system inhibitor, Residual Renal Function