Age-Related Adaptations in Renal Tubular Function in Female Rats

Pre-translational studies of mechanisms underlying chronic diseases in adult humans should ideally use animal models corresponding to mature adult rather than young animals. In this study, we examined the impact of age and past pregnancy on renal function in Sprague Dawley female rats.

In 4.5 month virgins and 12 month breeders, rates of glomerular filtration, urinary excretion, responses to diuretic and electrolyte challenges, and relative abundance of renal tubule transporters (per mg protein) were compared and simulations performed to determine the impact of age on tubular transport and energetics.

Twelve month versus 4.5 month females exhibited ~25% higher GFR, lower abundance of key Na⁺ transporters, higher AQP2 abundance, and comparable urinary excretion rates. Twelve month rats excreted a saline bolus slower than 4.5 month, yet excreted more Na⁺ following furosemide and hydrochlorothiazide challenges. In response to a 3% K⁺-rich meal, both age groups exhibited similar excretion profiles. With age, SGLT1 abundance rose while SGLT2 was unchanged. Sodium pump activity and Electron Transport Chain complex abundance were lower in 12 month versus 4.5 month rats. Model simulations suggest that as female rats age and breed, their kidneys adapt to larger filtration rates by expanding surface area and reabsorption capacity predominantly along the proximal nephron, where transport is most energetically efficient. The decrease in Na⁺ transporter abundance acts to counteract the effects of increased tubular size.

Our findings suggest a greater propensity for sodium retention in females with age, which warrants consideration for hypertension and kidney disease studies.