Dataset Information

Genetic Predisposition for Renal Dysfunction and Incidence of CKD in the Malmo Diet and Cancer Study.

ABSTRACT: Background:Genome-wide association studies (GWAS) have identified >50 single nucleotide polymorphisms (SNP) in association with estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD) but little is known about whether the combination of these SNPs may aid in prediction of future incidence of CKD in the population. Methods:We included 2301 participants with baseline eGFR ?60 mL/min per 1.73 m2 from the Malmö Diet and Cancer Study-Cardiovascular Cohort. The eGFR was estimated during baseline (1991-1996) and after a mean follow-up of 16.6 years using the CKD-Epidemiology Collaboration 2009 creatinine equation. We combined 53 SNPs into a genetic risk score weighted by the effect size (wGRSCKD), and examined its association with incidence of CKD stage 3A (eGFR ?60 mL/min per 1.73 m2). Results:At follow-up, 453 study participants were defined as having CKD stage 3A. We observed a strong association between wGRSCKD and eGFR at baseline (P = 6.5 × 10-8) and at the follow-up reexamination (P = 5.0 × 10-10). The odds ratio (OR) for incidence of CKD stage 3A was 1.25 per 1 SD increment in the wGRSCKD (95% confidence interval [CI]: 1.12-1.39) adjusting for potential confounders (sex, age, body mass index [BMI], baseline eGFR, fasting glucose, systolic blood pressure (SBP), antihypertensive treatment, smoking, follow-up time). Adding wGRSCKD on the top of traditional risk factors did not improve the C-statistics (P = 0.12), but the Net Reclassification-Improvement-Index was significantly improved (cNRI = 21.3%; 95% CI: 21.2-21.4; P < 0.0001). Conclusion:wGRSCKD was associated with a 25% increased incidence of CKD per 1 SD increment. Although the wGRSCKD did not improve the prediction model beyond clinical risk factors per se, the information of genetic predisposition may aid in reclassification of individuals into correct risk direction.

SUBMITTER: Schulz CA

PROVIDER: S-EPMC6698292 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Genetic Predisposition for Renal Dysfunction and Incidence of CKD in the Malmö Diet and Cancer Study.

Schulz Christina-Alexandra CA Engström Gunnar G Christensson Anders A Nilsson Peter M PM Melander Olle O Orho-Melander Marju M

Kidney international reports 20190516 8

<h4>Background</h4>Genome-wide association studies (GWAS) have identified >50 single nucleotide polymorphisms (SNP) in association with estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD) but little is known about whether the combination of these SNPs may aid in prediction of future incidence of CKD in the population.<h4>Methods</h4>We included 2301 participants with baseline eGFR ≥60 mL/min per 1.73 m<sup>2</sup> from the Malmö Diet and Cancer Study-Cardiovascular Cohor ...[more]

PMID: 31440704

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Project description:AIMS/HYPOTHESIS:Growth differentiation factor 15 (GDF-15) is an anti-inflammatory cytokine of the transforming growth factor-? superfamily. Circulating levels of GDF-15 are associated with hyperglycaemia among people with obesity or diabetes, but longitudinal evidence on the association between GDF-15 levels and diabetes risk is scarce. Our aim was to explore whether circulating levels of GDF-15 at baseline are positively associated with future diabetes incidence in a middle-aged urban population. METHODS:Between 1991 and 1994, baseline fasting plasma GDF-15 levels were measured in 4360 individuals without diabetes (mean age 57.4?±?5.96 years, 38.6% men) who were participants in the Malmö Diet and Cancer-Cardiovascular Cohort. After a follow-up of 19.0?±?5.16 years (mean?±?SD), Cox proportional hazards regression analysis was used for the study of the relationship between baseline GDF-15 and incident diabetes, with adjustment for established confounders. A sensitivity analysis included further adjustment for levels of C-reactive protein (CRP). RESULTS:During the follow-up period, 621 individuals developed diabetes. The multivariate-adjusted HR for diabetes incidence was 1.43 (95% CI 1.11, 1.83; p for trend = 0.007) for the fourth compared with the first quartile of GDF-15, and was 1.17 (95% CI 1.07, 1.28; p?<?0.001) per SD increase of GDF-15. If participants were grouped according to baseline fasting glucose, the association between GDF-15 and diabetes risk was only evident in the group without impaired fasting glucose (n?=?3973). The association tended to be less significant with increasing age: multivariate-adjusted HRs for diabetes per SD increase of GDF-15 were 1.24 (95% CI 1.08, 1.42), 1.19 (95% CI 1.00, 1.41) and 1.04 (95% CI 0.89, 1.23) for participants aged ?55, 56-60 (>55 and ?60) and >60 years, respectively. With adjustment for levels of CRP, the HR per SD increase of GDF-15 (1.21, 95% CI 1.09, 1.35) was significant (p?=?0.015), but the HR for the fourth compared with the first quartile of GDF-15 was not significant (HR 1.30; 95% CI 1.01, 1.67; p for trend = 0.061). CONCLUSIONS/INTERPRETATION:GDF-15 may be useful for identification of people with a risk of incident diabetes, especially if those people are ?60 years old.

Dataset Information

Genetic Predisposition for Renal Dysfunction and Incidence of CKD in the Malmo Diet and Cancer Study.

Publications

Genetic Predisposition for Renal Dysfunction and Incidence of CKD in the Malmö Diet and Cancer Study.

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