Mode of action in kidney disease

In kidney disease, the renin-angiotensin-aldosterone system (RAAS) is activated, which leads to progression of kidney dysfunction. Fortekor (benazepril hydrochloride) is nephroprotective by blocking the harmful effects of the RAAS and thus slowing disease progression.

RAAS activation produces angiotensin II, which causes constriction of the efferent arteriole as it leaves the glomerulus. This increases pressure within the glomerulus (glomerular hypertension) which, in turn, damages the glomerular membrane. Such damage to the glomerular membrane allows loss of protein into the urine (proteinuria) and eventually leads to loss of the nephron.

Fortekor blocks the RAAS, thus normalising glomerular hypertension and reducing proteinuria, while maintaining glomerular filtration rate (GFR).

  • Fortekor reduces glomerular pressure

Fortekor blocks the constriction of the efferent arteriole of the glomerulus caused by angiotensin II, reducing (normalising) the glomerular pressure and protecting the glomerular membrane from further damage. This, in turn, reduces urinary protein loss.

  • Fortekor maintains GFR

Whilst in theory the reduction in glomerular pressure should cause a fall in GFR, GFR is actually maintained,1 probably through beneficial effects on the basement membrane.

  • Fortekor reduces systemic hypertension

By blocking angiotensin II, Fortekor also causes systemic vasodilation, which slightly reduces systemic blood pressure. As patients with chronic kidney disease (CKD) are often hypertensive, this effect is beneficial in many cases.

Dual elimination

Fortekor is removed from the body both via the kidneys and the liver; in other words, it has dual elimination.

Fluffy Cat DSC3940

Where Fortekor is eliminated:

Dog: liver 50%/ kidneys 50%

Cat: liver 85%/ kidneys 15%

This is in contrast to other ACE inhibitors:

Enalapril is excreted 85-95% by the kidneys (dogs)

Ramipril is excreted 60% by the liver and 40% by the kidneys (dogs)

In animals with compromised renal function, there is a risk that drugs which are excreted almost entirely through the kidneys could accumulate, i.e. effectively an overdose. Therefore, drugs excreted through the kidneys may require dose adjustment.

A study has shown that, in both cats and dogs with renal compromise, there is no increased exposure to benazeprilat, therefore no dose adjustment of Fortekor is required.

Reference 1: S.A. Brown et al. (2001) Am J Vet Res, 62, 375-383.