Genetic Risk for Hypertension Increases the Effect of Salt Intake on the Risk of Incident CKD

Key Points A higher frequency of adding salt was significantly associated with an increased risk of CKD development in the high polygenic risk score-hypertension group. However, no significant association was observed between salt intake frequency and CKD in the low and intermediate polygenic risk score-hypertension groups. Background Although excessive salt intake increases the risk of adverse health outcomes, its effects may vary among individuals, supporting the concept of salt sensitivity. This study aimed to investigate whether genetic factors, represented by the polygenic risk score for hypertension (PRS-hypertension), could act as determinants of salt sensitivity and modify the effect of salt intake on incident CKD. Methods Data from UK Biobank were used, including participants of White British ancestry without preexisting CKD or hypertension. The primary exposures were the self-reported frequency of adding salt to food and the PRS-hypertension tertile group. The primary outcome was the development of CKD, analyzed using multivariable Cox models. Results Among 258,555 participants (mean age 55.3±8.1 years, 44% men), 8686 (3%) cases of incident CKD were observed during median follow-up of 13.7 years. A significant interaction was observed between PRS-hypertension and frequency of adding salt with respect to CKD risk ( P for multiplicative interaction = 0.001). In the high PRS-hypertension group, compared with those who rarely/never added salt to food, the adjusted hazard ratio was 1.11 (95% confidence interval [CI], 1.02 to 1.21) for those who sometimes added salt and 1.23 (95% CI, 1.14 to 1.36) for those who usually/always added salt. In addition, there were significant additive interactions between high PRS-hypertension and usually/always adding salt on the risk of incident CKD compared with those with low PRS-hypertension and who rarely/never added salt (relative excess risk due to interaction=0.19; 95% CI, 0.03 to 0.34; attributable proportion=0.15; 95% CI, 0.04 to 0.27). Conclusions PRS-hypertension modified the association between frequency of adding salt and incident CKD. These findings suggest that the effects of high sodium intake on kidney function may be influenced by genetic factors.