Angiotensin converting enzyme inhibitors have revolutionised the treatment of congestive heart failure,1 hypertension,2 and diabetic nephropathy.3 After myocardial infarction, treatment with angiotensin converting enzyme inhibitors decreases the incidence of life threatening left ventricular failure and improves survival.4 Yet, despite appearing to be a panacea for vascular diseases, angiotensin converting enzyme inhibitors may present a hazard for patients with unsuspected atherosclerotic renovascular disease,5 and the size of that risk may be growing.
Convention dictates that if the serum creatinine concentration is unchanged several days after starting an angiotensin converting enzyme inhibitor there is no haemodynamically important renal artery stenosis. But this scenario applies only in bilateral renovascular disease: in unilateral disease these drugs may cause ischaemic damage and loss of function of the affected kidney while the serum creatinine concentration remains stable. Not all cases of acute renal failure induced by angiotensin converting enzyme inhibitors are reversible.6
The prevalence of renovascular disease, once quoted as 1-5% in unselected hypertensive patients,7 is now thought to be higher.6,8 Increasingly, atherosclerotic renal artery stenoses are being identified in the presence of atherosclerosis elsewhere. In one study over 40% of patients with peripheral vascular disease had angiographic evidence of significant renovascular disease.5 Similarly, serious coexisting renal artery stenosis was present in about a fifth of patients with coronary artery disease, confirmed by coronary angiography.9 Renal artery stenosis may be more common in people with diabetes than had been assumed: a necropsy study showed clinically silent disease in nearly 10% of patients with type 2 diabetes mellitus.10
Ischaemic nephropathy is a major cause of end stage renal failure and may be more common than realised.6,11 In a prospective study of all patients starting renal replacement therapy in one unit over 18 months renal angiography revealed atherosclerotic renal artery stenosis in 14%,11 an incidence which may increase as many older patients are accepted on to programmes for end stage renal failure.
We do not know whether treatment with angiotensin converting enzyme inhibitors hastens the loss of renal function in the long term when given to people with unsuspected unilateral renovascular disease. Since clinical trials have shown overall benefit in preserving renal function in patients with diabetes—a group at high risk of renal artery stenosis—then either the theoretical potential for inducing ischaemic nephropathy has been exaggerated or angiotensin converting enzyme inhibitors can preserve function in the remaining healthy kidney. Alternatively, the results of these trials might have been even more impressive had patients with renovascular disease been excluded.
Atherosclerotic renal artery stenosis is a progressive disease: in a prospective study the incidence of progression from less than 60% stenosis to over 60% was 30%, 44%, and 48% at 1, 2, and 3 years respectively.12 With the continued increase in the prescription of angiotensin converting enzyme inhibitors, caution must be exercised to prevent iatrogenic loss of the renal mass. Renal angiography remains the gold standard for diagnosis,13 but renal duplex scanning offers a rapid, non-invasive test for screening for critical renal artery stenosis before starting treatment.12–14 Comparative studies show that duplex ultrasound scanning can reliably predict the presence or absence of significant renal artery stenosis,12,13 and colour Doppler ultrasonography may be even more sensitive.14
The success of angiotensin converting enzyme inhibitors in preventing and treating vascular disorders is undeniable. However, screening for unilateral renal artery stenosis might be wise before treatment is started in patients at high risk. These include hypertensive patients over 50 and those with peripheral vascular disease, diabetes, or coronary artery disease. When renovascular disease is identified the benefits of angiotensin converting enzyme inhibitors may still be available if treatment is started after percutaneous transluminal renal angioplasty and stent placement.
References
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