Specific Blockage of Angiotensine 2 and Podocyturia in Glomerular Nephropathies With Hypertension and Proteinuria

Study Overview
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Brief Summary
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Chronic glomerular diseases are one of the main causes leading to end stage renal disease (ESRD). Hypertension and proteinuria are two modifiable factors promoting the progression of ESRD. Podocyte are terminally differentiated epithelial cells and play a central role in the progression of chronic kidney disease and in the development of glomerulosclerosis. The presence of podocyte in urines (podocyturia) has been documented by several teams with continuous and regular podocyturia during glomerular disease. This facts suggests that podocyturia could become a marker of podocyte loss and glomerular damage. In our university hospital, we developed a technique to evaluate the number of microparticles (cellular fragments) in different biologic samples. The podocytary origin of microparticles will be determinated thanks to specific antibodies. The aim of the present study is: i) to quantify podocyturia during glomerular nephropathies by dosing podocyte microparticles ii) to study the relationship between podocyturia and other biologic markers such as proteinuria iii) to evaluate the effect of angiotensine 2 blockage on podocyturia. This is an open-labelled randomized monocenter cross-over study. Twenty subjects with hypertension and glomerular nephropathy characterized by proteinuria and a normal or slightly altered renal function will be included. Patients will be treated successively by an angiotensin receptor blocker (ARB), losartan and by a thiazide, hydrochlorothiazide, (after a wash out period). We will study the impact of these two therapies on podocyturia. Results will be compared with others markers like proteinuria (and its selectivity). We may finally dispose of a non invasive urinary marker of podocyte lesions responsible for glomerulosclerosis and for ESRD progression. Moreover mechanism of nephroprotection of the ARB may be more comprehensive.

Official Title
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Specific Blockage of Angiotensine 2 and Podocyturia in Glomerular Nephropathies With Hypertension and Proteinuria

Conditions
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Proteinuria, Hypertension, End Stage Renal Disease

Intervention / Treatment
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* Drug: losartan, hydrochlorothiazide
* Drug: hydrochlorothiazide, losartan


Participation Criteria
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Eligibility Criteria
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Hypertension (TAs > 130, TAd > 80mmHg or under antihypertensive treatment) Glomerular nephropathy, proteinuria > 1 g/day, serum creatinin < 200 µmol/L ; Informed consent given ; No contraindication for ARB and hydrochlorothiazide ; Efficient contraception for women

Ages Eligible for Study
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Minimum Age: 18 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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>losartan, hydrochlorothiazide | Drug: losartan, hydrochlorothiazide<br>* Two administrations of losartan per day,up to 100mg per day, during 2 months, followed by a wash-out during 1 month, and then one administration of hydrochlorothiazide, 25 mg per day during 2 months<br>|
| Active Comparator: 2<br>hydrochlorothiazide, losartan | Drug: hydrochlorothiazide, losartan<br>* One administration of hydrochlorothiazide, 25 mg per day during 2 months, followed by a wash-out during 1 month, and then, two administrations of losartan per day,up to 100mg per day, during 2 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Podocyturia |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proteinuria; |  |  | 
| selectivity index of proteinuria |  |  | 
| arterial blood pressure |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Podocyte - podocyturia - microparticles - angiotensin receptor antagonist - glomerulosclerosis, Patients presenting with stable glomerular nephropathy with proteinuria, normal or slightly altered renal function, with hypertension