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Introduction: Alstr?m syndrome is a rare recessive genetic disease caused by mutations in ALMS1 , which encodes a protein that is related to cilia function and intracellular endosome trafficking. The syndrome has been linked to impaired glucose metabolism and CKD. Polymorphisms in Alms1 have likewise been linked to CKD, but little is known about the modification of the phenotype by environmental factors. Methods: To gain further insights, the fat aussie （ foz ） mouse strain, a genetic murine model of Alstr?m syndrome, was exposed to a normal chow （NC） or to a Western diet （WD, 20% fat, 34% sucrose by weight, and 0.2% cholesterol） and renal outcomes were measured. Results: Body weight and albuminuria were higher in foz than in wild-type （WT） mice on both diets but WD significantly increased the difference. Measurement of plasma creatinine and cystatin C indicated that glomerular filtration rate was preserved in foz versus WT independent of diet. Renal markers of injury, inflammation, and fibrosis were similar in both genotypes on NC but significantly greater in foz than in WT mice on WD. A glucose tolerance test performed in foz and WT mice on WD revealed similar basal blood glucose levels and subsequent blood glucose profiles. Conclusions: WD sensitizes a murine model of Alstr?m syndrome to kidney injury, inflammation, and fibrosis, an effect that may not be solely due to effects on glucose metabolism. Polymorphisms in Alms1 may induce CKD in part by modulating the deleterious effects of high dietary fat and sucrose on kidney outcome.
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