Sex-specific Association With Kidney Disease

Diabetic Nephropathy Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01810822
• Other study ID #: FMUSP-LIM25-0002
• Status: Completed
• Phase: N/A
• First received: March 11, 2013
• Last updated: March 13, 2013
• Start date: May 1994
• Est. completion date: October 2012

Study information

• Verified date: March 2013
• Source: University of Sao Paulo General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: National Committee of Ethics in Research
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1396
• Est. completion date: October 2012
• Est. primary completion date: May 1994
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 11 Years and older

Eligibility

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 Design

Observational Model: Case-Only, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Diabetic Nephropathies
• Diabetic Nephropathy
• Kidney Diseases

Locations

Country	Name	City	State
Brazil	Faculty of Medicine from University of São Paulo	São Paulo	SP

Sponsors (1)

Lead Sponsor	Collaborator
University of Sao Paulo General Hospital

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Albumin to Creatinine Ratio		Two Years	Yes