Food processing has a greater effect than protein restriction or plant-based diets on early kidney disease progression in the pcy mouse model of polycystic kidney disease

Abstract

Much controversy surrounds the putative benefits of protein restriction or plant- versus animal-based diets in the prevention and treatment of kidney disease. Meanwhile, ultra-processed food (UPF) consumption is increasingly being linked to chronic disease progression. Therefore, the objectives of this study were to examine the effects of, firstly, food processing, protein restriction and plant-based diets made with human foods, and secondly, the highly processed AIN93G standard laboratory rodent diet, on early kidney disease progression in the pcy mouse model of polycystic kidney disease (PKD). Mice (n=128) were randomly allocated to groups in a 2 [UPF or whole-food (WF)] × 2 (15% or 8% protein by calories) × 2 (animal- or plant-based) × 2 (male or female) design. Each group received three different macronutrient-balanced menus, rotated weekly. The proportion of dietary UPF was within the fourth to fifth quintiles of typical Canadian intake, and the animal-based diets reflected Canadian consumption, where about two-thirds of protein comes from animal sources. An additional pair-weighed group (n=16) received a restricted amount of the UPF, 15% protein, animal-based diet. The final group (n=16) was provided the AIN93G diet, for a total of 160 mice. After 16 weeks, cyst volume was assessed as the primary measure of PKD progression. Cyst volumes (μL/g lean body weight) were 64% higher in mice provided UPF compared to WF diets, but were not affected by protein level or food source. Further, the urine neutrophil gelatinase-associated lipocalin (NGAL) marker of tubular injury was 58% higher in mice provided UPF compared to WF diets. Urine protein and osmolality, and serum creatinine, urea, bicarbonate, Na, K, Cl, and P were not correlated to disease, as measured by cyst volume. Food restriction in the pair-weighed group reduced both adiposity and NGAL. Additionally, mice provided the AIN93G versus WF diets had more than 2-fold higher cyst volumes and NGAL, suggesting that the AIN93G may need re-evaluation to provide a healthier diet for experimental studies. In conclusion, food processing has a greater effect than protein level or food source on early kidney disease progression, indicating that increased WF consumption may be recommended for individuals with PKD.