Phenylbutyrate in Proteinuric Nephropathies

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether sodium phenylbutyrate can reduce Lcn2 urinary expression in proteinuric patients.

Detailed Description
-----------------
Proteinuria is a major prognosis factor of chronic kidney disease (CKD) progression. Convergent evidences from clinical and experimental studies indicate that albuminuria and proteinuria are not simply a marker of CKD progression, but an active player in the evolution of the disease. Mechanistically, it has been shown that proteinuria induces endoplasmic reticulum stress in tubular cells, leading to induction of lipocalin 2/NGAL, a critical element of CKD progression. Moreover, proteinuric mice treated with phenylbutyrate are protected from CKD progression. The aim of this study is to evaluate the efficacy of phenybutyrate, a molecular chaperone which inhibits ER stress, on the proteinuria-induced NGAL expression. Urinary NGAL/creatinine ratio will be evaluated in proteinuric patients before and under treatment with phenylbutyrate.

Official Title
-----------------
Phenylbutyrate Effect on Lcn2 Urianry Expression in Proteinuric Patients

Conditions
-----------------
Proteinuric Diseases

Intervention / Treatment
-----------------
* Drug: PBA 7,5g/d
* Drug: PBA 15g/d


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Chronic Kidney disease for ore than 3 months Proteinuria > 1g/d or 0,1g/mmmol creatinine eGFR >30ml/mn/1,73m2 written informed consent affiliated with social security health insurance Exclusion Criteria: Women with childbearing potential Recent (<3 months) modification of ACE inhibitors or ARB Acute renal failure eGFR <30ml/mn/1,73m2 Nephrotic syndrome (albuminélia <30g/l) Infection with HIV, HCV, HBV Liver insufficiency No affiliated with social security health insurance inclusion in another protocol of biomedical research risk of non-adherence to protocol and visits patients having a cardiac insufficiency of grade 3 or 4 patient requiring of a strict salt-free diet patients under corticoids or immunosuppresseurs clinical intolerance in the treatment intolerance in the fructose, the syndrome of malabsorption glucose and galactose or a deficit in sucrase / isomaltase patients treated by Probenecide

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

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

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

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PBA 7,5g/d<br>Treatment for 14 days | Drug: PBA 7,5g/d<br>* Treatment for 14 days with PBA<br>|
| Experimental: PBA 15g/d<br>Treatment for 14 days | Drug: PBA 15g/d<br>* Treatment for 14 days with PBA<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary Lcn2/creatinine ratio | Reduction of 50 % of Lcn2 concentration, measured with ELISA | Day 7, Day 15, Day 21, Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary protein/creatinine ratio | Reduction of 30% of the proteinurie and the albuminuria | Day 7 | 
| Urinary protein/creatinine ratio | Reduction of 30% of the proteinurie and the albuminuria | Day 15 | 
| Urinary protein/creatinine ratio | Reduction of 30% of the proteinurie and the albuminuria | Day 21 | 
| Urinary protein/creatinine ratio | Reduction of 30% of the proteinurie and the albuminuria | Day 28 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Proteinuria, Lipocalin 2, Neutrophil gelatinase associated lipocalin, ELISA