Genetic risk scores (GRS) improve the prediction power of classical risk factors for mortality in general population. However, it is unknown whether GRS improve the prognostic power of simple risk prediction tools (i.e. risk scores, RS) in ESKD patients.
In 188 hemodialysis patients (aged 59 yrs), we genotyped 124 polymorphisms in 54 genes which resulted to be associated with mortality in ESKF patients and/or in diabetics and in patients with CV diseases. Four polymorphisms [rs708259 (FTO gene); rs1047214 (NPY2R gene); rs4807546 (SIRT6 gene); rs1044498 (ENPP1gene)] significantly predicted mortality in our cohort. As an index of global genetic burden, we calculated a weighted GRS by summing up the number of risk alleles recoded in rank order and estimated the increase in prognostic power when GRS was added to a RS for mortality recently validated in ESKD patients (Kidney Int 2015;87:996-1008).
The RS (median:3, IQR:1-6) and GRS (median:0.6, IRQ:0.3-0.8) were slightly inter-related (rho=0.12,P=0.09). During the follow-up (3.9 yrs), 129 patients died (40% of cardiovascular causes). On crude Cox analyses, both RS [hazard ratio (HR) (1 unit):1.13, 95%CI:1.08-1.18, P<0.001] and GRS [HR:2.29, 95%CI: 1.40-3.75,P=0.001] significantly predicted mortality. The RS-based model (basic model) provided a 65% discriminatory power for death and a 27% explained variation in mortality. When GRS was added into the basic model, both risk scores [RS, HR:1.12, 95%CI:1.07-1.17,P<0.001; GRS, HR:1.80, 95%CI:1.10-2.95,P=0.02] significantly predicted the occurrence of death. The inclusion of GRS improved (P<0.02) discrimination (from 65% to 66%) and explained variation (from 27% to 31%) of the basic model. Of note, GRS produced a 15% NRI and 3% IDI (P<0.03).
A GRS including four polymorphisms improves the prediction power for mortality of a well-validated RS in hemodialysis patients and represents proof of concept of the potential value of GRS for refining prognosis in this population.
