Renal artery stenosis, defined as narrowing of the renal artery or arteries, can be uni- or bilateral.
There are two likely pathological processes at work: atherosclerosis and fibromuscular dysplasia.
Atherosclerosis accounts for approximately 70-90 per cent of renal artery stenosis and tends to occur in men over the age of 50. Risk factors are similar to those for cardiovascular disease. Up to 5 per cent of hypertensive patients may have renovascular disease.
The remainder of renal artery stenosis cases are caused by fibromuscular dysplasia, which is seen more frequently in younger females. In this condition, stenosis is bilateral in 60 per cent of cases and, unlike vascular renal artery stenosis, tends to occur in mid- and distal renal arteries.
Except for ACE inhibitor-induced reduction in renal function, renal artery stenosis may present with resistant hypertension (most hypertension in these patients is not renovascular in origin), pulmonary oedema, renal failure (with or without hypertension), or clinically in vasculopaths or those with abdominal bruits.
Proteinuria below nephrotic range (ACR<250) may be the only presenting feature.
Diagnostic techniques include captopril stimulation tests, ACE inhibitor renography, duplex ultrasound, CT, MRI and angiography. Duplex ultrasound has up to a 98 per cent specificity and sensitivity. Conventional ultrasound may demonstrate shrunken (<8cm) kidneys.
The optimal treatment modality for renal artery stenosis is still debated. Studies have demonstrated at least a 20-32 per cent reduction in creatinine with surgical intervention.1,2
Thrombosis and re-stenosis may affect about 4 per cent of patients. Percutaneous intervention has superseded open surgery and long-term outcome studies have shown little difference between the two groups.3
All patients with atherosclerotic renal artery stenosis should have their vascular risk factors managed. Antiplatelet drugs should be prescribed and calcium-channel blockers may be used as an effective alternative for BP control. ACE inhibitors should be used with caution.
Benefits and risks
ACE inhibitors were developed in the 1970s and have revolutionised the management of renal and cardiac diseases. Unfortunately, as with most drugs, there are side-effects and contra-indications (including significant aortic and renal artery stenosis).
First-dose hypotension may be particularly marked in those who are already volume depleted.
A dry irritating cough, caused by elevated pulmonary bradykinin, is more commonly seen in women and can affect up to one in five patients. As the cough may be particularly troublesome at night, obstructive airways disease should be excluded.
Voice changes, taste alteration, angioedema, abdominal pain, rash, blood dyscrasias and hyperkalaemia are also seen.
Reduced blood glucose is a well documented side-effect and ACE inhibitors may account for nearly 14 per cent of hypo-glycaemia-related admissions.
While ACE inhibitors have been shown to be effective in certain kidney disorders, in some conditions, such as renal artery stenosis, they and ARBs may adversely affect renal function.
Other conditions that predispose to acute renal failure with ACE inhibitors include chronic renal diseases, such as polycystic kidney disease, cardiac failure, hypovolaemia and cirrhosis. ACE inhibitors may also cause renal tubular acidosis and renal artery thrombosis.
Mechanism of action
ACE inhibitors suppress the activity of ACE, an enzyme central to the renin-angiotensin-aldosterone (RAAS) system.
Renin is stimulated by a reduction in renal perfusion, as in renal artery stenosis or low BP, changes in sodium concentration, prostaglandin changes and neurohormonal sympathetic stimulation.
Once released into the circulation, renin cleaves angiotensinogen to form the biologically inactive angiotensin I. ACE then cleaves two more amino acids to form angiotensin II, a process that occurs primarily in the lungs. ACE is also involved in the breakdown of bradykinin.
Angiotensin II stimulates the adrenal cortex to produce aldosterone. It is a powerful biological vasoconstrictor.
Angiotensin II forms part of the renal autoregulation of glomerular perfusion mechanism. The preglomerular arteriolar tone is reduced when renal perfusion falls, increasing glomerular blood flow and maintaining glomerular filtration.
If this response is inadequate, renin is released, activating the RAAS cascade, leading to angiotensin II mediated constriction of the post-glomerular arteriole. Pressure within the glomerulus is therefore increased and filtration restored.
Renal artery stenosis
In renal artery stenosis, the afferent pressure is reduced by the narrowed vessel, hence autoregulation is almost exclusively dependent on changes in post-glomerular arteriolar tone.
Because ACE inhibitors interfere with the production of angiotensin II, autoregulation is impaired, glomerular perfusion falls, renal ischaemic nephropathy develops and renal failure ensues.
ACE inhibitors are very effective when treating renovascular hypertension, especially in combination with diuretics, as long as there is no significant deterioration in eGFR (>25 per cent reduction in eGFR or >30 per cent increase in creatinine).4 Renal function and potassium should be checked before starting an ACE inhibitor.
If creatinine exceeds 150micromol/L, NICE recommends that these drugs should only be introduced under specialist supervision.4
Particular care should be taken in at-risk groups, including those with known vascular disease and patients taking diuretics or antihypertensives who may be on the verge of iatrogenic renal hypoperfusion.
Bloods should be checked approximately 10 days after starting ACE inhibitors and after each increase. Patients should be started at the lowest dosage and up-titrated.
Up to half of patients with bilateral renal artery stenosis will have a mild decline in eGFR, although other renal diseases may behave in a similar way. A mild increase in creatinine is acceptable and may demonstrate the efficacy of ACE inhibitors.
About 5-10 per cent of patients will have a significant reduction in eGFR. A 30 per cent or greater rise in creatinine or a 20 per cent fall in eGFR is suspicious and referral for further investigation should be considered, along with stopping the ACE inhibitor or ARB. Renal artery stenosis often presents this way.
In patients who have critical artery stenosis, ACE inhibitors may precipitate acute renal failure, requiring urgent intervention. In the context of chronic heart failure, NICE suggests that a 50 per cent rise in creatinine above pre ACE inhibitor levels, or an increase to 200micromol/l, may be acceptable.5
- Dr Thakkar is a GP in Wooburn Green, Buckinghamshire
1. Rimmer J M, Gennari F J. Atherosclerotic renovascular disease and progressive renal failure. Ann Intern Med 1993; 118(9): 712-9.
2. Reilly J M, Rubin B G, Thompson R W et al. Revascularization of the solitary kidney. Surgery 1996; 120(4): 732-6.
3. Erdoes L S, Berman S S, Hunter G C et al. Comparative analysis of percutaneous transluminal angioplasty and operation for renal revascularization. Am J Kidney Dis 1996; 27(4): 496-503.
4. NICE CG73. Chronic kidney disease. London: NICE, 2008.
5. NICE CG5. Chronic heart failure. London: NICE, 2003.