Emerging Cardiovascular Therapies-Exploiting the Link Between Heart and Kidney

Blood pressure is tightly regulated by interactions between the heart, kidneys and systemic vasculature. These are under neurohumoral, paracrine and autocrine control. Novel treatments for human diabetic nephropathy are now providing insight into these regulatory pathways through their unexpected beneficial and adverse effects. These therapies may soon enter the veterinary armamentarium.
Endothelin A (ETA) receptor antagonists, such as atrasentan, reduce blood pressure, glomerulosclerosis and proteinuria in diabetic nephropathy, but, paradoxically, promote sodium and water retention.
Sodium glucose transporter 2 (SGLT2) inhibitors, such as dapagliflozin, are diuretics that promote urinary sodium and glucose excretion to aid weight loss and increase insulin sensitivity. However, beneficial reductions in proteinuria, blood pressure and cardiovascular risk are independent of blood glucose status, and phase III clinical trials have demonstrated reductions in mortality risk in non-diabetic patients with heart failure and chronic kidney disease.
The mechanisms that underpin all these effects remain elusive but pre-clinical studies suggest that they are translatable across species. This paves the way towards a significant impact in companion animals in which the incidence of cardiac and renal disease is high.
This talk will discuss current thinking on the regulation of blood pressure in people, and how this is applicable to cats and dogs. The unexpected consequences of ETA and SGLT2 inhibition will be described within the context of cardiac and renal interactions, before outlining the translatable potential of these agents, to aid management of congestive heart failure, chronic kidney disease, pulmonary hypertension and cardiorenal syndrome.