Hypoxia-inducible factor
prolyl hydroxylase (HIF-PHD) inhibitors were developed for treatment of renal
anemia. Patients applicable for HIF-PHD inhibitor treatment experience complications such as
chronic kidney disease, whereby water and
electrolyte homeostasis is disrupted. The effects of
hypoxia-inducible factor stabilization on
salt accumulation in the setting of reduced renal function remain unclear. In the present study, we investigated the effect of a HIF-PHD inhibitor,
molidustat, on
salt distribution and excretion in rats with subtotal
nephrectomy-induced
chronic kidney disease. Male Wistar rats were subjected to 5/6
nephrectomy. After confirming blood pressure elevation (>150 mmHg, at 4 weeks after surgery), rats were treated with
molidustat. After 1 week of treatment,
molidustat did not significantly improve blood cell volume or blood pressure. Distribution of
sodium,
potassium, and water in skin, carcass, and bone samples was not affected by
molidustat. Furthermore,
molidustat had no significant effect on urinary
sodium excretion or concentration in response to acute oral
salt loading (1 g/kg). In conclusion,
molidustat did not affect distribution or excretion of
salt in rats subjected to a model of nephron loss.