Combined effects of diet and genetic predisposition on kidney function outcomes

Background: Chronic kidney disease (CKD) is a significant global health concern. While diet is crucial to CKD prevention and management, the interaction between diet and genetic predisposition to CKD is underexplored. We conducted an exploratory investigation of the interplay between a polygenic score (PGS) for kidney function and dietary exposures in relation to glomerular filtration rate estimated based on serum creatinine (eGFRcrea) on 5717 generally healthy adult participants of the Cooperative Health Research In South Tyrol study. Methods: Dietary intake was assessed using the GA2LEN food frequency questionnaire, from which we derived dietary quality indices including the Mediterranean, Alternative Healthy Eating Index and Dietary Approaches to Stop Hypertension diets, and nutrients relevant to kidney function (proteins, potassium and phosphorus). Genetic predisposition to lower kidney function was quantified using a PGS derived from 131 single nucleotide polymorphisms whose risk alleles were associated with lower eGFRcrea and higher blood urea nitrogen. We fitted multivariable generalized additive models incorporating diet-by-PGS interaction terms to model nonlinear associations with eGFRcrea. Results: The PGS was linearly associated with eGFRcrea (estimated degrees of freedom, df = 1.00, P < .0001), regardless of dietary exposures. All nutrients showed significant linear negative associations with eGFRcrea, a pattern not observed for dietary indices. Nominally significant nonlinear interactions were observed between the PGS and both protein (df = 4.93, P = .0298) and phosphorus intake (df = 5.37, P = .0283). Conclusions: The association of dietary protein and phosphorus intake with eGFRcrea may vary by genetic predisposition to low eGFRcrea levels, with stronger dietary effects in those with a high genetic predisposition.