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The genetic risk of kidney disease in type 2 diabetes.

ABSTRACT: For more than 20 years, evidence in favor of a genetic basis for the susceptibility of DN in T2D has provided a foundation for studies aimed at identifying the causal genes responsible for its development. During this period, strategies used to map genes for DN have been driven by our understanding of variation across our genome and the technologies available to interrogate it; as both have evolved, so to have our approaches. The advent of next-generation sequencing technology and increased interest in the search for rare variants has begun to swing the pendulum of these efforts away from population-based studies and back to studies of pedigrees. As the field moves forward, family based approaches should greatly facilitate efforts to identify variants in genes that have a major affect on the risk of DN in T2D. To be successful, the ascertainment and comprehensive study of families with multiple affected members is critical.

SUBMITTER: Pezzolesi MG

PROVIDER: S-EPMC3539136 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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The genetic risk of kidney disease in type 2 diabetes.

Pezzolesi Marcus G MG Krolewski Andrzej S AS

The Medical clinics of North America 20121207 1

For more than 20 years, evidence in favor of a genetic basis for the susceptibility of DN in T2D has provided a foundation for studies aimed at identifying the causal genes responsible for its development. During this period, strategies used to map genes for DN have been driven by our understanding of variation across our genome and the technologies available to interrogate it; as both have evolved, so to have our approaches. The advent of next-generation sequencing technology and increased inte ...[more]

PMID: 23290732

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Project description:BackgroundData on the relations between kidney function abnormalities and stroke in type 2 diabetes are limited. We evaluated the associations of kidney function abnormalities and chronic kidney disease (CKD) stages with incident stroke in a large sample of adults with type 2 diabetes.MethodsParticipants with type 2 diabetes from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study without history of stroke at baseline were included. Urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) were assessed at baseline. CKD categories were defined according to the KDIGO (Kidney Disease: Improving Global Outcomes) guidelines. Cox proportional hazards regression models were used to compute hazard ratios (HR) and 95% confidence intervals (CI) for stroke in relation to measures of kidney function and CKD categories.ResultsA total of 9170 participants (mean age 62.8 [SD: 6.6] years, 38.2% women, 62.9% white) were included. Over a median follow-up of 4.9 years (interquartile range: 4.0-5.7), 156 participants developed a stroke (incidence rate 3.6/1000 person-years [95% CI 3.0-4.2]). After adjusting for relevant confounders, higher UACR and lower eGFR were each associated with increased risk of stroke. Compared to UACR < 30 mg/g, moderate albuminuria and severe albuminuria were associated with increasing hazards for stroke (HR 1.61 [95% CI 1.12-2.32] and 2.29 [95% CI 1.39-3.80], respectively). Compared to eGFR of ≥ 60 mL/min/1.73 m2, decreased eGFR (eGFR < 60 mL/min/1.73 m2) was associated with higher risk of stroke (HR 1.50, 95% CI 0.98-2.29). Compared to no CKD, worsening CKD stage was associated with an increasing risk of stroke (HRs of 1.76 [95% CI 1.10-2.83] for CKD G1, 1.77 [95% CI 1.13-2.75] for CKD G2, and 2.03 [95% CI 1.27-3.24] for CKD G3).ConclusionsIn a large sample of adults with type 2 diabetes, increasing albuminuria and worsening stages of early CKD were independently associated with higher risk of incident stroke.Trial registrationClinicalTrials.gov. Identifier: NCT00000620 .

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The genetic risk of kidney disease in type 2 diabetes.

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The genetic risk of kidney disease in type 2 diabetes.

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