A DING1, S WALTON2, K MORITZ2,3, J PHILLIPS1
1Department of Biomedical Science, Macquarie University, Sydney, Australia, 2School of Biomedical Sciences, University of Queensland, Brisbane, Australia, 3Child Health Research Centre, University of Queensland, Brisbane, Australia
Aim: To determine if improved pre-and/or postnatal environment can reduce the severity of renal and cardiovascular disease in a rodent model of polycystic kidney disease (PKD).
Background: Maternal insufficiency during foetal development can have long-lasting effects on the offspring, most notably on nephron endowment. PKD and nephronophthisis (NPHP), characterised by cystic kidneys and comorbidities such as hypertension, show variability in severity of disease and maternal environment may be a modifying factor. We hypothesized PKD leads to reduced nephron number which can be ameliorated by improved pre-and/or postnatal environment, reflected by enhanced overall health.
Method: Using the Lewis Polycystic Kidney (LPK) rodent model of NPHP, we examined nephron number in homozygous LPK (LPK -/-) vs. Lewis wildtype (LPK +/+) age 12 weeks. We then compared phenotype (body weight, blood pressure and renal function at age 16 weeks, n = 6♂/6♀ per group) and nephron number in LPK rats born from and raised by LPK dams (control), LPK cross-fostered onto heterozygous LPK (+/-) dams (postnatal improvement), LPK born from and raised by heterozygous LPK dams (pre and postnatal improvement) or heterozygous Wistar Kyoto WKY/LPK dams (pre and postnatal improvement on different genetic background).
Results: Nephron numbers were 25% lower in LPK compared to wildtype (14095±453 vs. 18564±980, p<0.05, n=10). Improvement in pre-and postnatal environment improved growth, renal function and reduced blood pressure, most notably in animals on the different genetic background. Animals with improved postnatal environment only showed improved growth and blood pressure but to a lesser extent. All intervention groups showed increased nephron number compared to LPK control.
Conclusions: Pre-and postnatal environment has a significant impact on the severity and progression of PKD, including nephron endowment.
Jacqueline Phillips is Professor of Neurophysiology in the Department of Biomedical Science in the Faculty of Medicine and Health Science at Macquarie University. Jacqueline’s research in autonomic and sensory neuroscience is focussed on perturbations in central and peripheral control of the cardiovascular system in renal disease and the drivers of high blood pressure in this condition. Her studies use a rodent model of cystic kidney disease to answer these questions. Jacqueline’s research is multidisciplinary, using assessment of structure and function in both acute and chronic studies.