What effect do Angiotensin-Converting Enzyme (ACE) inhibitors have on glomerular filtration rate (GFR) in patients with renal artery stenosis?

Effect of ACE Inhibitors on GFR in Renal Artery Stenosis

In renal artery stenosis, angiotensin-converting enzyme (ACE) inhibitors will decrease glomerular filtration rate (GFR) due to their predominant effect on efferent arteriolar vasodilation, which reduces glomerular capillary pressure. 1

Mechanism of Action

• In renal artery stenosis, maintenance of GFR becomes highly dependent on angiotensin II (Ang II), which constricts the efferent arteriole to a greater extent than the afferent arteriole, thereby maintaining glomerular hydrostatic pressure despite reduced renal perfusion 1
• ACE inhibitors block the formation of Ang II, leading to vasodilation of the efferent arteriole, which reduces intraglomerular pressure and subsequently decreases GFR 1
• This effect is particularly pronounced in high-grade bilateral renal artery stenosis or stenosis of a dominant or single kidney 1

Pathophysiological Effects

• When ACE inhibitors are administered in renal artery stenosis, they cause:

  • Predominant efferent arteriolar vasodilation 1
  • Reduction in glomerular capillary pressure 1
  • Decreased filtration fraction 2
  • Potential development of acute renal failure (ARF) 1

• The decrease in GFR occurs because:

  • Renal perfusion pressure cannot be sustained due to the stenosis 1
  • The compensatory effect of Ang II on the efferent arteriole is blocked 1
  • Autoregulation of GFR is impaired 3

Clinical Implications

• ACE inhibitor-induced reduction in GFR can be detected through:

  • Elevated serum creatinine levels 1
  • Kidney scintigraphy showing reduced function in the affected kidney 4, 5
  • Decreased split renal function on captopril renography 5

• Risk factors for significant GFR reduction include:

  • Bilateral renal artery stenosis or stenosis of a dominant/single kidney 1
  • Volume depletion (e.g., from diuretic therapy) 1
  • Pre-existing hypotension 1
  • Concomitant use of NSAIDs or other vasoconstrictor agents 1

Management Considerations

• A 10-20% increase in serum creatinine is commonly observed and expected after initiating ACE inhibitor therapy in patients with renal insufficiency 1
• In renal artery stenosis, the decrease in GFR may be more pronounced and potentially lead to acute renal failure 1
• Monitoring serum creatinine and electrolyte levels before and one week after starting ACE inhibitor therapy is recommended 1
• ACE inhibitor-induced renal dysfunction typically reverses with discontinuation of the medication or volume replenishment 1

Important Caveats

• The effect of ACE inhibitors on GFR differs between patients with renal artery stenosis and those with other conditions:

  • In patients with heart failure without renal artery stenosis, ACE inhibitors may improve or maintain GFR 1
  • In patients with chronic kidney disease without renal artery stenosis, the initial decrease in GFR is usually transient and followed by stabilization or improvement due to renoprotective effects 1
  • In renal artery stenosis, the decrease in GFR may be persistent and significant 3

• While ARBs (Angiotensin Receptor Blockers) work through a similar mechanism, some research suggests they may have protective effects on the poststenotic kidney despite causing an initial decrease in GFR 6