Dietary fructose and high salt in young male Sprague Dawley rats induces salt‐sensitive changes in renal function in later life

Dietary fructose and salt are associated with hypertension and renal disease. Dietary input during critical postnatal periods may impact pathophysiology in maturity. The highest consumption of fructose occurs during adolescence. We hypothesized that a diet high in fructose with or without high salt in young male Sprague Dawley rats will lead to salt‐sensitive hypertension, albuminuria, and decreased renal function in maturity. Four groups were studied from age 5 weeks: 20% glucose + 0.4% salt (GCS‐GCS) or 20% fructose + 4% salt throughout (FHS‐FHS). Two groups received 20% fructose + 0.4% salt or 20% fructose + 4% salt for 3 weeks (Phase I) followed by 20% glucose + 0.4% salt (Phase II). In Phase III (age 13–15 weeks), these two groups were challenged with 20% glucose + 4% salt, (FCS‐GHS) and (FHS‐GHS), respectively. Each group fed fructose in Phase I exhibited significantly higher MAP than GCS‐GCS in Phase III. Net sodium balance, unadjusted, or adjusted for caloric intake and urine flow rate, and cumulative sodium balance were positive in FHS during Phase I and were significantly higher in FCS‐GHS, FHS‐GHS, and FHS‐FHS vs GCS‐GCS during Phase III. All three groups fed fructose during Phase I displayed significantly elevated albuminuria. GFR was significantly lower in FHS‐FHS vs GCS‐GCS at maturity. Qualitative histology showed mesangial expansion and hypercellularity in FHS‐FHS rats. Thus, fructose ingestion during a critical period in rats, analogous to human preadolescence and adolescence, results in salt‐sensitive hypertension and albuminuria in maturity. Prolonged dietary fructose and salt ingestion lead to a decline in renal function with evidence suggestive of mesangial hypercellularity.