Your browser has javascript turned off or blocked. This will lead to some parts of our website to not work properly or at all. Turn on javascript for best performance.

The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Default user image.

Olle Melander

Principal investigator

Default user image.

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

Author

  • Christina Alexandra Schulz
  • Gunnar Engström
  • Anders Christensson
  • Peter M. Nilsson
  • Olle Melander
  • M. Orho-Melander

Summary, in English

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.

Department/s

  • Diabetes - Cardiovascular Disease
  • Cardiovascular Research - Epidemiology
  • EpiHealth: Epidemiology for Health
  • Internal Medicine - Epidemiology
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • Cardiovascular Research - Hypertension

Publishing year

2019-05-16

Language

English

Pages

1143-1151

Publication/Series

Kidney International Reports

Volume

4

Issue

8

Document type

Journal article

Publisher

Elsevier Inc.

Topic

  • Nutrition and Dietetics
  • Family Medicine

Keywords

  • CKD
  • eGFR
  • GRS
  • renal function

Status

Published

Research group

  • Diabetes - Cardiovascular Disease
  • Cardiovascular Research - Epidemiology
  • Internal Medicine - Epidemiology
  • Cardiovascular Research - Hypertension

ISBN/ISSN/Other

  • ISSN: 2468-0249