Sex-specific Association With Kidney Disease

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.

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT01810822

Enrollment

1396

Registered

2013-03-14

Start date

1994-05-31

Completion date

2012-10-31

Last updated

2013-03-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diabetic Nephropathy

Keywords

oxidative stress, genetic susceptibility, GPX4, NOX2

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.

Interventions

None listed

Study design

Observational model

CASE_ONLY

Time perspective

CROSS_SECTIONAL

Eligibility

Sex/Gender

ALL

Age

11 Years to No maximum

Healthy volunteers

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).

Design outcomes

Primary

Measure	Time frame
Albumin to Creatinine Ratio	Two Years

Countries

Brazil

Outcome results