Phenylbutyrate in Proteinuric Nephropathies

Phenylbutyrate Effect on Lcn2 Urianry Expression in Proteinuric Patients

The purpose of this study is to determine whether sodium phenylbutyrate can reduce Lcn2 urinary expression in proteinuric patients.

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.

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