Atorvastatin in the Recipient's Kidney Graft From a Living Donor (ATORV15)

Effectiveness of Atorvastatin on IL2, IL6, TNFalpha and HLA Levels in the Recipient's Kidney Graft From a Living Donor

Renal insufficiency is a priority disease in the health system, which may require renal replacement therapy based on kidney transplantation, which is considered as therapy of choice. During the procedure of kidney transplantation, the body is subjected to ischemia-reperfusion damage that generates late complications related to graft function.

Recently the anti-inflammatory and immunomodulatory effects of statins have been emphasized, which could be beneficial in kidney transplantation.

Study Overview

• Status: Completed
• Conditions: Renal Insufficiency
• Intervention / Treatment: Drug: Atorvastatin; Drug: Placebo

Detailed Description

Objective: Evaluate the effect of atorvastatin on IL2, IL6, TNFalpha and HLA levels in the recipient's kidney graft from a living donor.

Material and methods: Controlled, double-blind trial with 12 months follow-up. Composed of 48 patients, randomized manner, realized at the Transplant Department of Western Medical Center, Mexican Institute of Social Security. Universe was patients accepted as kidney donors and their recipients. Patients included as donors were randomized into two groups (study or control) the intervention was implemented 4 weeks before kidney transplant. During surgical procedure, a biopsy from the recipient's kidney graft was obtained to measure IL-2, IL-6 TNFalpha and HLA by immunohistochemistry, 3 and 12 months after surgery. Recipients kidney function, surgical complications and kidney graft survival were registered. During surgical procedure, 3 and 12 months of following, biopsies were obtain to performed histopathological analysis based on Banff classification of renal allograft rejection grades.

The statistical analysis was performed according to the nature of variables, for continuous data using measures of central tendency and dispersion and for the qualitative data with frequencies and percentages. Inferential analysis with student's t-test, and/or Mann-Whitney's U test; chi-square distribution, and/or Fisher's exact test respectively.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 3

Contacts and Locations

Study Locations

• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44340
      • Western Medical Center, Mexican Institute of Social Security

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Donors Inclusion Criteria:

• Accepted as kidney donor
• Voluntary participation
• Informed consent accepted
• 85% fulfillment of atorvastatin treatment
• Entitlement to the Mexican Institute of Social Security

Donors Exclusion Criteria:

• Hypersensibility to Atorvastatin
• Smoking

Recipients Inclusion Criteria:

• Accepted as kidney recipient
• Entitlement to the Mexican Institute of Social Security

Recipients Exclusion Criteria:

• Patients who dropped out from study or withdrew the informed consent
• Insufficient kidney biopsy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Atorvastatin; 24 patients received oral atorvastatin 40 mg once a day, for 4 weeks.	Drug: Atorvastatin; Patients were assigned to two groups; one of them received oral atorvastatin (study group), and the other homologated placebo (control group) for 4 weeks before transplant. Then IL2, IL6, TNFalpha and HLA levels were assessed in the recipient's kidney graft by visual analog scale at prior reperfusion, and after 3 and 12 months.; Other Names: Lipitor
Placebo Comparator: Placebo; 24 patients received oral placebo 40 mg once a day, for 4 weeks.	Drug: Placebo; Patients were assigned to two groups; one of them received oral atorvastatin (study group), and the other homologated placebo (control group) for 4 weeks before transplant. Then IL2, IL6, TNFalpha and HLA levels were assessed in the recipient's kidney graft by visual analog scale at prior reperfusion, and after 3 and 12 months.; Other Names: Homologated placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HLA levels in the kidney graft biopsy	HLA levels were measure by immunohistochemistry, observing alteration between groups.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal function	In a blood sample and in a urine 24-hour collection, serum creatinine, serum urea, creatinine clearance, urine output, and proteinuria were measure. Differences in evolution and alteration between the 2 groups were registered.	12 months
Kidney graft survival	In a renal biopsy using the Banff classification of renal allograft rejection grades, were assessed histologic and molecular features by microscopy and immunofluorescence. Alterations between groups were registered.	12 months
Surgery complications	During surgical procedure and following, any kind of complication was registered.	12 months
TNFalpha levels in the kidney graft biopsy	TNFalpha levels were measure by immunohistochemistry, observing alteration between groups.	12 months
IL2 and IL6 levels in the kidney graft biopsy	IL2 and IL6 levels were measure by immunohistochemistry, observing alteration between groups.	12 months

Collaborators and Investigators

• Sponsor: Instituto Mexicano del Seguro Social
• Investigators: Principal Investigator: Clotilde Fuentes-Orozco, PhD, Instituto Mexicano del Seguro Social

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): January 1, 2018

Study Registration Dates

• First Submitted: August 7, 2015
• First Submitted That Met QC Criteria: August 12, 2015
• First Posted (Estimate): August 13, 2015

Study Record Updates

• Last Update Posted (Actual): September 10, 2018
• Last Update Submitted That Met QC Criteria: September 7, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Kidney Transplantation; Atorvastatin; Human Leukocyte Antigens; Interleukin
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: R-2013-1301-100