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

Effect of ACE Inhibitors on Glomerular Filtration Rate in Renal Artery Stenosis

In renal artery stenosis, angiotensin-converting enzyme (ACE) inhibitors decrease glomerular filtration rate (GFR) by causing efferent arteriolar vasodilation, which reduces intraglomerular pressure. 1, 2

Pathophysiological Mechanism

• 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 2
• ACE inhibitors block the formation of Ang II, leading to vasodilation of the efferent arteriole, which reduces intraglomerular pressure and subsequently decreases GFR 1
• Under these circumstances, blood is shunted from the afferent arteriole to the efferent arteriole because there is not adequate hydrostatic pressure to maintain filtration 1
• The glomerular filtration rate falls but renal blood flow changes very little, resulting in a decreased filtration fraction 1

Clinical Implications

• ACE inhibitors can cause acute renal failure in patients with bilateral renal artery stenosis, stenosis to a solitary kidney, or decompensated congestive heart failure in a sodium-depleted state 1
• A rise in serum creatinine of 10-20% is commonly observed after initiating ACE inhibitor therapy in patients with renal insufficiency 1, 2
• The risk of ACE inhibitor-induced acute renal failure is higher in patients with:
  • High-grade bilateral renal artery stenosis or stenosis of a dominant/single kidney 1
  • Volume depletion from diuretic therapy 1
  • Systemic hypotension (MAP ≤65 mm Hg) 1
  • Concomitant use of NSAIDs or other vasoconstrictor agents 1, 2

Diagnostic Value

• Severe hypotension or azotemia provoked by ACE inhibitors can provide a diagnostic clue to the presence of renal artery stenosis 1
• In patients with unilateral renal artery stenosis, ACE inhibitors may cause a selective decrease in GFR in the affected kidney despite well-preserved renal blood flow 3
• This effect forms the basis for captopril renal scintigraphy, which can be useful in detecting renovascular hypertension 4

Management Considerations

• ACE inhibitors should be discontinued temporarily while precipitating factors for acute renal failure are corrected 1
• Once acute renal failure has resolved with correction of the precipitating factors, ACE inhibitor therapy can be reinstituted in some cases 1
• Monitoring of serum creatinine early after initiation of therapy is recommended 1, 2

Important Distinctions

• In patients with essential hypertension without renal artery stenosis, ACE inhibitors may actually increase GFR despite lowering blood pressure 5
• 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 long-term renoprotective effects 2, 6

This pathophysiological understanding explains why ACE inhibitors decrease GFR in renal artery stenosis through their effect on efferent arteriolar tone, while they may preserve or improve GFR in other conditions.