Sex-specific Association With Kidney Disease

Completed

• Conditions: Diabetic Nephropathy

• Registration Number: NCT01810822
• Lead Sponsor: University of Sao Paulo General Hospital

Brief 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.

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 Timeline

• Study Start: 1994-05
• Primary Completion: 1994-05
• Study Completion: 2012-10
• Status Verified: 2013-03
• Study First Submitted: 2013-03-11
• Study First Submitted QC: 2013-03-13
• Last Update Submitted: 2013-03-13
• Study First Posted: 2013-03-14
• Last Update Posted: 2013-03-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1396

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

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Albumin to Creatinine Ratio	Two Years

Trial Locations

Locations (1)

Faculty of Medicine from University of São Paulo; 🇧🇷 São Paulo, SP, Brazil