A Polygenic Score for Reduced Kidney Function and Adverse Outcomes in a Cohort with Chronic Kidney Disease

Chronic kidney disease (CKD) is a global health burden of increasing importance that affects >10% of the general adult population.(1) CKD is defined as the sustained presence of abnormalities of kidney structure or function, and it is classified using estimated glomerular filtration rate (eGFR) and the urinary albumin-to-creatinine ratio.(S1) The eGFR based on serum creatinine is the most common measure of kidney function. Persons with CKD are at increased risk of adverse outcomes, such as kidney failure (KF), cardiovascular diseases, and premature death.(S2) Genome-wide association studies enable the calculation of polygenic scores (PGSs). PGSs aggregate the effects of many genetic variants into a single number and permit a straight-forward investigation of the association between a genetic predisposition with a given outcome. Yet, evaluations of such PGSs in external studies, including different target populations, are often limited. Large CKD cohorts, like the prospective German Chronic Kidney Disease(2) study, represent a valuable opportunity to study whether a PGS for reduced eGFR (termed "eGFR PGS") is associated with adverse outcomes in CKD, and whether the PGS adds information above and beyond established risk factors. Therefore, the aim of this study was to investigate if (i) a polygenic predisposition to lower eGFR is associated with KF, major adverse cardiovascular events (3P-MACE), and mortality in persons with CKD and if (ii) the eGFR PGS carries predictive ability by itself and in addition to established risk factors.