Sex-specific Association With Kidney Disease

March 13, 2013 updated by: University of Sao Paulo General Hospital

Sex-specific Associations of Variants in the Regulatory Regions of NADPH Oxidase-2 (CYBB) and Gluthatione Peroxidase 4 (GPX4) Genes With Kidney Disease in Type 1 Diabetes.

Oxidative stress is involved in the pathophysiology of diabetic nephropathy. The superoxide-generating nicotinamide adenine dinucleotide phosphate-oxidase 2 (NOX2, encoded by the CYBB gene) and the antioxidant enzyme glutathione peroxidase 4 (GPX4) play opposing roles in the balance of cellular redox status. In the present study, we investigated associations of single nucleotide polymorphisms (SNPs) in the regulatory regions of CYBB and GPX4 with kidney disease in patients with type 1 diabetes.

Study Overview

Status

Completed

Conditions

Detailed Description

In the present study, three cohorts of type 1 diabetic patients (one Brazilian and two French/Belgium cohorts) were studied for the association with diabetic nephropathy (DN) with a total of 1396 patients. The patients were classified according to the urinary albumin-to-creatinine ratio (ACR) or urinary albumin excretion rate (UAER) in absence of nephropathy, defined as ACR <30 mg/g or UAER < 20 µg/min or < 20 mg/L and plasma creatinine <1.7 mg/dL; incipient nephropathy, defined as persistent microalbuminuria (ACR 30 - 300 mg/g of creatinine or UAER 20 - 200 µg/min or 20 - 200 mg/L) and plasma creatinine <1.7 mg/dL; established diabetic nephropathy, defined as past or present macroalbuminuria (ACR >300 mg/g of creatinine or UAER >200 µg/min or > 200 mg/L) and plasma creatinine <1.7 mg/dL; advanced diabetic nephropathy, defined as past or present macroalbuminuria, plasma creatinine >1.7 mg/dL and any renal replacement therapy. Genotyping of polymorphisms was performed by Real Time PCR using fluorescent-labelled probes.

Study Type

Observational

Enrollment (Actual)

1396

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
    • SP
      • São Paulo, SP, Brazil, 01246-000
        • Faculty of Medicine from University of Sao Paulo

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

11 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Three cohorts pf type 1 diabetic patients were used for the present study. The first one is a Brazilian cohort with 451 patients recruited in diabetes/endocrinology departments of three university hospitals in the cities of São Paulo (SP), Campinas (SP) and Porto Alegre (RS), Brazil between October 2004 and October 2012. The second one is a French/Belgium cohort with 501 patients recruited from both countries between November 1998 to December 2000. The third cohort is a French/Belgium cohort with 444 patients recruited from both countries between May 1994 to April 1995.

Description

Inclusion Criteria:

  • Overt 10 years of Diabetes Mellitus (Brazilian cohort)
  • Diagnostic of diabetes before the age of 35 years, with initial ketosis and requirement for permanent insulin treatment within 1 year of diagnosis and past or present diagnosis of diabetic retinopathy. (Genesis cohort).
  • Diagnostic of diabetes before the age of 35 years and past or present diagnosis of severe diabetic retinopathy. (GENEDIAB cohort).

Exclusion Criteria:

  • Patients presenting autoimmune diseases, HIV or HCV infections (Brazilian cohort)
  • Patients with glomerular filtration rate < 60 mL min-1 1.73 m2 without diabetic retinopathy (Brazilian cohort)
  • Terminal cancer and personal disability (GENEDIAB cohort).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Only
  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort
Genesis French-Belgium Study
Cross-sectional, multi-center, binational (Belgian and France) study designed to evaluate the genetic components of diabetic nephropathy. It is a cohort with 501 patients, including 279 individuals (55.7%) with diagnosis of diabetic nephropathy.
GENEDIAB
Cross-sectional, multi-center, binational (Belgian and France) study designed to evaluate the genetic components of diabetic nephropathy. It is a cohort with 444 patients, including 310 individuals (69.8%) with diagnosis of diabetic nephropathy.
Brazilian cohort
The cohort comprised 451 patients with type 1 diabetes for more than 10 years (56% women; aged 36 ± 11 years, mean ± SD) recruited in diabetes/endocrinology departments of three university hospitals in the cities of São Paulo (SP), Campinas (SP) and Porto Alegre (RS), Brazil.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Albumin to Creatinine Ratio
Time Frame: Two Years
Two Years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Sao Paulo General Hospital

Investigators

  • Study Director: Maria L Côrrea-Giannela, Doctor, Clinical Hospital/Faculty of Medicine from University of São Paulo
  • Study Director: Gilberto Velho, Doctor, INSERM U695

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 1994

Primary Completion (Actual)

May 1, 1994

Study Completion (Actual)

October 1, 2012

Study Registration Dates

First Submitted

March 11, 2013

First Submitted That Met QC Criteria

March 13, 2013

First Posted (Estimate)

March 14, 2013

Study Record Updates

Last Update Posted (Estimate)

March 14, 2013

Last Update Submitted That Met QC Criteria

March 13, 2013

Last Verified

March 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FMUSP-LIM25-0002

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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