Phenylbutyrate in Proteinuric Nephropathies (PIRATE)

Assistance Publique - Hôpitaux de Paris

Status and phase

Completed

Phase 3

Phase 2

Conditions

Proteinuric Diseases

Treatments

Drug: PBA 15g/d

Drug: PBA 7,5g/d

Study type

Interventional

Funder types

Other

Identifiers

NCT02343094

2013-003924-35

Details and patient eligibility

About

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

Full 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.

Enrollment

26 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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