Abstract P329: Age- and Sex-differences in Salt Sensitivity and Renal Function in a Rat Model of Autosomal Recessive Polycystic Kidney Disease

Abstract

Background: Most forms of hypertension are influenced by gender and salt sensitivity, however, the interplay of these two factors and their functional consequences in polycystic kidney disease (PKD)-associated hypertension are poorly understood. Thus, we tested the hypothesis that age and male sex would pre-dispose animals with PKD to hypertension and risk of renal dysfunction. Methods: We used the Pkhd1 pck rat model of autosomal recessive PKD to study sex differences in blood pressure in response to a high salt diet (HSD). Two month- and eight month-old male and female Pkhd1 pck rats were surgically implanted with telemetry transmitters and allowed to recover for at least one week before obtaining baseline mean arterial pressure (MAP). Rats were maintained on either HSD (4% NaCl) or normal rat chow (0.49% NaCl) for 3 weeks. At the end of the study, rats were placed in metabolic cages and a 24 hr urine sample was collected before measuring GFR (transdermal sinistrin clearance). Results: In the 2-month old Pkhd1 pck rats, blood pressures were in a normal range and there were no differences between males and females. Furthermore, 3 weeks on a HSD had no effect on 24 hr MAP. GFR was similar between male and female rats on either diet. However, urinary protein excretion was significantly higher in HSD fed rats compared to normal rat chow in both male (83±26 vs. 17±4 mg/day, respectively, p<0.05) and female rats (106±25 vs. 6±2 mg/day, p<0.05). In 8-month old rats, again there were no sex differences between animals on normal rat chow. However, MAP increased progressively in male rats after 3 weeks of HSD feeding, a change that was significantly greater than females (Δ39±6 vs Δ15±5 mmHg, p<0.05). The blood pressure increase in male rats was associated with higher urinary protein excretion compared to female rats (755±118 vs. 390±48 mg/day, p<0.05). HSD significantly reduced GFR in male, but not female rats (0.48±0.13 vs. 1.24±0.05 mL/min/100 g bwt, respectively, p<0.05). GFR was similar between older male and female rats on normal salt diet. Summary: Our studies demonstrate that male Pkhd1 pck rats with advanced cystic kidney disease are more vulnerable to salt sensitive hypertension and renal injury than age-matched females.