ACE Inhibitors in Bilateral Renal Artery Stenosis: Mechanism of Contraindication
ACE inhibitors are contraindicated in bilateral renal artery stenosis because they cause acute renal failure by decreasing transglomerular hydrostatic pressure and glomerular filtration rate through efferent arteriolar dilation in kidneys that are critically dependent on angiotensin II for maintaining filtration. 1
Pathophysiological Mechanism
In bilateral renal artery stenosis, maintenance of glomerular filtration rate (GFR) becomes highly dependent on angiotensin II, which preferentially constricts the efferent arteriole to maintain glomerular hydrostatic pressure despite reduced renal perfusion 2
ACE inhibitors block the formation of angiotensin II, leading to vasodilation of the efferent arteriole, which reduces intraglomerular pressure and subsequently decreases GFR 2, 1
When ACE inhibitors are administered in bilateral renal artery stenosis, blood is shunted from the afferent arteriole to the efferent arteriole because there is not adequate hydrostatic pressure to maintain filtration 1
This effect is particularly pronounced in high-grade bilateral renal artery stenosis or stenosis of a dominant or single kidney, where the GFR is especially dependent on angiotensin II 1, 2
Clinical Consequences
Use of ACE inhibitors or angiotensin receptor blockers in patients with bilateral RAS, stenosis to a solitary kidney, or decompensated heart failure in a sodium-depleted state can result in acute renal failure 1
Clinically significant azotemia has been defined as a greater than 50% rise in serum creatinine that persists or worsens after hypoperfusion states are corrected 1
The development of severe hypotension or azotemia after starting ACE inhibitors provides a diagnostic clue to the presence of renal artery stenosis 1
This form of acute renal failure most commonly develops shortly after initiation of ACE inhibitor therapy but can be observed after months or years of therapy 1
Risk Factors for ACE Inhibitor-Induced Renal Failure
Bilateral renal artery stenosis or stenosis of a dominant/single kidney 2, 3
Pre-existing hypotension 2
Concomitant use of NSAIDs or other vasoconstrictor agents 2
Management Considerations
Bilateral renal artery stenosis, or a unilateral stenosis in a patient with only one kidney, is an absolute contraindication to ACE inhibition 3
In patients with unilateral renal artery stenosis and two kidneys, ACE inhibitors are considered second-line antihypertensives, with diuretics, beta-blockers, and calcium-channel blockers being first-line options 3
ACE inhibitor-induced renal dysfunction typically reverses with discontinuation of the medication or volume replenishment 2, 4
Patients with bilateral renal artery stenoses that have been successfully revascularized using renal stenting may be safely treated with long-term ACE inhibitor therapy 5
Diagnostic Implications
The sudden deterioration in renal function following initiation of therapy with an ACE inhibitor is a clue to the possible presence of bilateral renal artery stenosis or stenosis of a solitary functioning kidney 6
A captopril renal scan with hippuran and DTPA can provide physiological information regarding the renal blood flow and GFR of each kidney, helping to diagnose renovascular hypertension 6, 7
Monitoring serum creatinine and electrolyte levels before and one week after starting ACE inhibitor therapy is recommended to detect significant GFR reduction 2
Important Distinctions
In patients with heart failure without renal artery stenosis, ACE inhibitors may improve or maintain GFR 2
In patients with chronic kidney disease without renal artery stenosis, the initial decrease in GFR with ACE inhibitors is usually transient (10-20% increase in serum creatinine) and followed by stabilization or improvement due to long-term renoprotective effects 2, 4