Cardiorenal Effecs of Losartan in Kidney Transplant Recipients

Study Overview
=================
Brief Summary
-----------------
The influence of Losartan to cardiovascular and renal outcomes in patients after renal transplatation.

Detailed Description
-----------------
The benefits of cardio and nephroprotective properties of treatment with drugs blocking the renin angiotensin aldosterone system in the general population has already been shown. There are no data on the cardiac and renal effects of this type of treatment in patients after renal transplantation. Therefore, the observational, case-control study was designed in a population of kidney transplant recipients. The study group consists of patients treated with antihypertensive drugs including Losartan at a minimum dose of 50mg. The control group consists of patients treated with antihypertensive drugs, without the renin angiotensin aldosterone system blockade. Blood pressure will be controlled in accordance with the current recommendations. The primary aim of this study is to determine whether, in renal transplant recipients with hypertension, losartan, angiotensin II receptor antagonist improves cardiovascular and graft outcome i.e. reduces incidence of cardiovascular complications and slows progression of graft insufficiency. Secondary objective is to determine whether losartan 1. delays the occurrence of cardiovascular complications, 2. slows progression of graft insufficiency, 3. is the safe drug in renal transplant recipients, 4. decrease albuminuria and other surrogate markers of graft injury or cardiovascular involvement.

Official Title
-----------------
Cardiorenal Effecs of Losartan in Kidney Transplant Recipients

Conditions
-----------------
Renal Transplant Failure, Cardiovascular Complication

Intervention / Treatment
-----------------
* Drug: Losartan


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 740 patients, either sex, either non-diabetic or diabetic who underwent the kidney transplantation and who: Are at least three months post-transplantation Have hypertension. Have an estimated glomerular filtration rate greater than or equal to 30 ml/min/1.73 m2 Exclusion Criteria: Pregnant or the possibility of becoming so and breast feeding. Angioedema from an Angiotensin Converting Enzyme (ACE) inhibitor or Angiotensin Receptor Blocker (ARB) in the history. Serum potassium greater than 5.5 mmol/l on two or more occasions in the preceding three months. Graft artery stenosis (i.e. psv of more than 200 cm/s in doppler usg) Left ventricular dysfunction that requires an ACE inhibitor or an ARB New immunosuppressive agent was started or previous immunosuppressant stopped in the three months prior to study entry or plan to switch immunosuppressive agents within next three months. Currently on four or more blood pressure pills and have an average blood pressure over three visits greater than 150/100. Currently on an ACE-inhibitor or an ARB or treatment with an ACE inhibitor or ARB after kidney transplantation lasted more than 3 months. Had an acute coronary syndrome, episode of malignant hypertension, stroke or transient ischaemic attack in the three months prior to study entry.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Study group<br>Hypotensive treatment including Losartan | Drug: Losartan<br>* losartan treatment<br>* Other names: Lozap, Lorista, Xartan, Losacor;|
| Control group<br>Hypotensive treatment without renin-angiotensin-aldosteron system blockers. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of composite primary endpoint: | Cardiovascular (CV) death and Resuscitated sudden death and Non-fatal myocardial infarction (MI) and Non-fatal stroke and Unplanned hospitalization for heart failure or unstable angina and Onset of end-stage renal disease (ESRD) and Doubling of baseline serum creatinine concentration, sustained for at least one month. | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of cardiovascular complications | Cardiovascular (CV) death and Resuscitated sudden death and Non-fatal myocardial infarction (MI) and Non-fatal stroke and Unplanned hospitalization for heart failure or unstable angina | Up to 5 years | 
| Occurrence of renal complications | ESRD or doubling of baseline serum creatinine | Up to 5 years | 
| Decline in estimated glomerular filtration rate (eGFR) | Difference in degree of eGFR reduction | Up to 5 years | 
| Urine albumine concentration | Difference in albuminuria in the measurements available for each patient | after 6 months | 
| N-acetyl-β-D-glucosaminidase (NAG) urine excretion | Difference in urine NAF in the measurements available for each patient | after 6 months | 
| 15-F2t-isoprostanes (isoprostanes) urine excretion | differences in 15-F2t-isoprostanes (isoprostanes) urine excretion in the measurements available for each patient | after 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
kidney transplant recipients, albuminuria, cardiovascular disease, nephroprotection, angiotensin receptor blocker