Proteinuric Diseases
Conditions
Keywords
Proteinuria, Lipocalin 2, Neutrophil gelatinase associated lipocalin, ELISA
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.
Interventions
DRUGPBA 7,5g/d
Treatment for 14 days with PBA
DRUGPBA 15g/d
Treatment for 14 days with PBA
Sponsors
URC-CIC Paris Descartes Necker Cochin
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Urinary Lcn2/creatinine ratio | Day 7, Day 15, Day 21, Day 28 | Reduction of 50 % of Lcn2 concentration, measured with ELISA |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Urinary protein/creatinine ratio | Day 7 | Reduction of 30% of the proteinurie and the albuminuria |
Countries
France
Outcome results
None listed