Sex and the ageing kidney- paper out now!

Protective role of female gender in programmed accelerated renal aging in the rat

Wioletta Pijacka, Bethan Clifford, Chantal Tilburgs, Jaap Joles, Simon Langley-Evans and Sarah McMullen

Physiological Reports 3, e12342


Mean arterial blood pressure (MAP) and heart rate (HR) in control (CON) and low‐protein (MLP) intact (SHAM) and ovariectomized (OVX) offspring at 12 months of age. Data were collected continuously over a 5 day period by radiotelemetry and means calculated to give a 24 h profile. A two‐way ANOVA looking at the diet and ovariectomy effects showed that MAP was the lowest in the CON‐SHAM during light cycle, (*P < 0.05 compared to CON‐SHAM) and there was a tendency for it to be lower over full 24 h period, P = 0.06. HR was significantly increased in OVX group (***P < 0.001 compared to OVX of same dietary background).

The aging kidney exhibits a progressive decline in glomerular filtration rate, accompanied by inflammatory and oxidative damage. We hypothesized that accelerated, age-related progression of renal injury is ovarian hormones-dependant. To address this we used an established model of developmentally programmed accelerated renal aging in the rat, superimposed by ovariectomy to assess interactions between ovarian hormones and the aging process. Under our experimental conditions, we found that kidney function worsens with age, that is GFR reduces over 18 month analyzed time-course and this was worsened by fetal exposure to maternal low-protein diet and absence of estrogen. Reduction in GFR was followed by increases in albuminuria, proteinuria, inflammatory markers, and tissue carbonyls, all suggesting inflammatory response and oxidative stress. This was associated with changes in AGTR2 expression which was greater at 18 months of age compared to earlier time points, but in MLP offspring only. Our studies show an influence of ovarian hormones on programmed accelerated renal aging and the AGTR2 across the lifespan. The main findings are that ovariectomy is a risk factor for increased aging-related renal injury and that this and oxidative damage might be related to changes in AGTR2 expression.