Genetic Risk Scores Identify People at High Risk of Developing Diabetic Kidney Disease: A Systematic Review

J Clin Endocrinol Metab. 2024 Apr 19;109(5):1189-1197. doi: 10.1210/clinem/dgad704.

Abstract

Context: Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. Measures to prevent and treat DKD require better identification of patients most at risk. In this systematic review, we summarize the existing evidence of genetic risk scores (GRSs) and their utility for predicting DKD in people with type 1 or type 2 diabetes.

Evidence acquisition: We searched MEDLINE, Embase, Web of Science, and Cochrane Reviews in June 2022 to identify all existing and relevant literature. Main data items sought were study design, sample size, population, single nucleotide polymorphisms of interest, DKD-related outcomes, and relevant summary measures of result. The Critical Appraisal Skills Programme checklist was used to evaluate the methodological quality of studies.

Evidence synthesis: We identified 400 citations of which 15 are included in this review. Overall, 7 studies had positive results, 5 had mixed results, and 3 had negative results. Most studies with the strongest methodological quality (n = 9) reported statistically significant and favourable findings of a GRS's association with at least 1 measure of DKD.

Conclusion: This systematic review presents evidence of the utility of GRSs to identify people with diabetes that are at high risk of developing DKD. In practice, a robust GRS could be used at the first clinical encounter with a person living with diabetes in order to stratify their risk of complications. Further prospective research is needed.

Keywords: diabetic kidney disease; genetic risk score; polygenic risk score.

Publication types

  • Systematic Review

MeSH terms

  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / diagnosis
  • Diabetes Mellitus, Type 2* / genetics
  • Diabetic Nephropathies* / diagnosis
  • Diabetic Nephropathies* / epidemiology
  • Diabetic Nephropathies* / etiology
  • Genetic Risk Score
  • Humans
  • Kidney Failure, Chronic* / complications