Patients with chronic kidney disease and asymptomatic hyperuricemia on the balance of mechanisms of vascular injury and repair. MedDRA version: 16.1 Level: LLT Classification code 10007648 Term: Cardiovascular disease, unspecified System Organ Class: 100000004849
Conditions
Interventions
Trade Name: Alopurinol
Product Name: Alopurinol
Product Code: 616789
Pharmaceutical Form: Capsule
INN or Proposed INN: ALLOPURINOL
CAS Number: 315-30-0
Other descriptive name: ALLOPURINOL
Concentratio
Sponsors
Fundación Para la Investigación Biomédica de Córdoba
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patient willing and able to give informed consent for participation in the study. - Ability to understand study procedures and to comply with it for the duration of the study. - Subjects of both sexes, the age range between 18 and 70 years old. - Serum uric acid than 7 mg / dl. - Estimated glomerular filtration rate by MDRD abbreviated formula less than 60 ml / min/1.73m2 and above 15 ml/min/1.73m2. - Stability of renal function (serum creatinine increase without exceeding 50% in the three months before the start of the study). - Clinically stable in terms of no hospitalizations or cardiovascular events in the 3 months before the study began. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 25 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
Exclusion criteria: - Drop active in the 60 days prior to study initiation. - Use of allopurinol within 60 days preceding baseline - Active infections within 30 days prior to baseline. - Patients with systemic inflammatory disease. - Infection with HIV, Hepatitis C and Hepatitis B. - History of cancer within 5 years prior to the first dose of study medication. - Chronic liver disease. - Immunosuppressive therapy. - Pregnant women, breastfeeding, or planning to become pregnant. - Allergy or sensitivity to allopurinol. - Addiction to drugs or alcohol, in the opinion of the investigator, may interfere with compliance with study requirements. - Inability or unwillingness of the individual or legal guardian or representative to give written informed consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To study the effect of inhibiting xanthine oxidase with allopurinol in patients with chronic kidney disease in asymptomatic hyperuricemia endothelial injury and vascular repair mechanisms, evaluating the plasma concentration of angiogenic factors, microparticles of endothelial cells and the cell number circulating endothelial progenitor.;Secondary Objective: To study the effect of inhibition of xanthine oxidase with allopurinol in patients with chronic kidney disease and asymptomatic hyperuricemia on the following variables: - Oxidative stress - Microinflammation - Endothelial dysfunction - Blood Pressure - Glomerular filtration ratio - Microalbuminuria / proteinuria;Primary end point(s): Microinflammation: C-ReactiveProtein, IL-1, IL-6, CD14+ CD16+ monocytes Oxidative stress and cellular damage markers: Reactive oxygen species (ROS). Transmembrane mitochondrial potential loss. To characterize the DNA damage associated with an increase in ROS activity, we will analyze 84 genes involved in signaling pathways of DNA damage. These genes are primarily related to intracellular signaling pathway ATR / ATM, as well as markers associated with genomic damage that will result in cell cycle arrest, apoptosis, and stabilization and repair the cellular genome. This study will be done through microarray (Human DNA Damage Signaling RT ² Profiler ? PCR Array, abiosciences) Endothelial dysfunction: Endothelium-dependent vasodilation will be assessed by measuring the change in skin blood flow using Laser Doppler Flowmetry technique with Periflux System 5000. Lesion / repair vascular mechanism: ICAM, VCAM, VEGF, endothelial cell microparticles, endothelial progenitor circulating cells.;Timepoint(s) of evaluation of this end point: after each patient visits | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Blood pressure: Assessed by 24 hours ambulatory blood pressure monitoring. Estimated Glomerular filtration rate: Assessed by MDRD-4 and Cockroft-Gault. Microalbuminuria / proteinuria: Assessed by urinary albumina/creatinine ratio and urinary protein / creatinine ratio, in the first morning void.;Timepoint(s) of evaluation of this end point: after each patient visits | — |
Countries
Spain
Contacts
Public ContactIsabel Bejerano Blazquez
Fundación Para la Investigación Biomédica de Córdoba
Outcome results
None listed