Abstract
Background & Objectives:
Chronic kidney disease (CKD) affects >10% of the global population and has a major inheritable component. Diet plays a key role in CKD prevention and management. However, the interaction between diet and CKD genetic predisposition is largely unexplored. We investigated the interaction between a kidney function polygenic score (PGS) and several dietary variables in association with the creatinine-based estimated glomerular filtration rate (eGFR), which defines CKD, in the Cooperative Health Research in South Tyrol (CHRIS) study.
Material and methods:
We included 5,901 CHRIS study participants without CKD and related comorbidities (median age=40 years; 53% females), who self-completed the GA2LEN food frequency questionnaire. We derived eGFR (median eGFR=102 ml/min/1.73m2), as a marker for renal function. We estimated the Dietary Approach to Stop Hypertension (DASH) index, reflecting overall diet quality, and five CKD-relevant nutrients: protein, phosphorus, phosphorus-to-protein ratio, potassium, and sodium. The PGS was derived from a large genome-wide association study meta-analysis of eGFR (n=562,799). We fitted multiply-adjusted generalized additive models on eGFR, incorporating tensor product smooths and diet-PGS interaction terms to model non-linear associations.
Results:
The PGS and the DASH index explained 5.7% and 2.3% of eGFR variance, respectively. We observed non-linear associations between eGFR, PGS (P<0.0001) and DASH index (P=0.044). All nutrients, except sodium, were linearly negatively associated with eGFR. We observed significant interactions of the PGS with protein intake (P=0.027) and phosphorus-to-protein ratio (P=0.006): protein intake and phosphorus-to-protein ratio were associated with eGFR levels only in individuals with high PGS, showing lower eGFR levels at high protein intake and low phosphorus-to-protein ratio.
Conclusions:
The effect of protein intake on CKD varies with the genetic predisposition to CKD.