Scoping Review of Polygenic Risk Scores in Kidney-Related Traits

Large-scale genome-wide association studies (GWAS) have identified numerous loci associated with various diseases and traits, enabling the development of polygenic risk scores (PRS) and genetic risk scores (GRS) that capture cumulative effects of variants. Although these scores have been applied in nephrology, no review has systematically evaluated their implementation or performance. This review aimed to summarize the current landscape of PRS and GRS related to kidney traits and diseases.

In April 2025, we searched PubMed, Embase, Scopus, and Web of Science for peer-reviewed articles and preprints following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Review guidelines. Studies were included if they developed or evaluated PRS and GRS for kidney-related traits. Data on study characteristics, score construction, and performance metrics were extracted.

Of the 1947 records identified, 104 met the inclusion criteria, encompassing 129 unique scores or evaluations. The most frequently studied traits were chronic kidney disease (CKD, n = 43) and estimated glomerular filtration rate (eGFR, n = 18). Additional outcomes such as albuminuria, eGFR rate slope, end-stage kidney disease (ESKD), acute kidney injury (AKI), and specific subgroups of CKD, were evaluated in a few studies. The key challenges include a marked ancestry imbalance, with a predominance of European populations, modest incremental predictive performance for CKD, and frequent mismatches between derivation traits and evaluated outcomes.

Current evidence suggests that the clinical utility of PRS and GRS in nephrology depends on the context. Improved diversity, phenotype definition, and methodological standardization are essential for enhancing translational potential.