ACE-inhibitors are well-established in treatment of hypertension. In recent years selective angiotensin II AT₁-receptor antagonists have been introduced as an alternative. Although the same system is manipulated, the two types of medication differ in several ways. In brief, the major differences are: 1) whereas blockade of angiotensin II formation by ACE-inhibition is incomplete due to alternative synthesis pathways, e.g. chymase pathway, angiotensin II antagonists block the receptors at the target organ, 2) the relative effect on AT₁- and AT₂-receptors, and 3) differential effect on bradykinin metabolism since ACE inhibition inhibits ACE inactivation of bradykinin. The latter is thought to be the major reason for the higher rate of side-effects seen with ACE inhibitors compared to angiotensin II antagonists. Whereas the evidence that ACE-inhibitors should be avoided in patients with renal artery stenosis is substantial, the evidence is more sparse with regard to angiotensin II antagonists and restricted to losartan.

A 60 years old male with previous alcohol abuse and known hypertension for the last 5 years was admitted to our hospital with a diagnosis of hypertension. At the time of admission the blood pressure (BP) was 230/140 mmHg despite treatment with metoprolol (Selozok), amiloride/hydrochlorthiazide (Sparkal Mite) and candesartan (Atacand). The patient was hyperkalemic and had an increased serum-creatinine (237 μmol/l). Antihypertensive treatment was intensified including addition of loop-diuretic and hydration.

It is well established that ACE inhibitors should be avoided in patients with critical renal artery stenosis. In contrast, this is not as well established with respect to angiotensin II antagonists. Over the last years a few cases have shown that renal function may be impaired if the angiotensin II antagonist losartan is used in patients with renal artery stenosis [1,2,3,4] but two of these cases were in the special situation of kidney transplants [3,4]. To our knowledge we are the first to report a case of renal impairment induced by the angiotensin II antagonist candesartan. Subsequent to the introduction of losartan, several other angiotensin II blockers have been marketed over the last couple of years and differences in receptor affinity and kinetics are reported. Therefore, our case supports the thought that caution should be shown using other types of angiotensin II antagonists. As mentioned in the introduction several differences exist between ACE inhibitors and angiotensin II, AT₁-receptor antagonists. Therefore, differences with regard to interference with renal function and thereby when the compound should be avoided could exist. From a theoretical point of view however, one would expect that both principles of blockade should be avoided in renal artery stenosis. The mechanism of the renin-angiotensin system in regulation of renal function is believed primarily to be due to the effect of angiotensin II on the efferent arteriolar tone keeping the pressure relatively constant in the glomerulus and thereby keeping GFR constant over a wide range of perfusion pressures, i.e. systemic BP. However, the differential effect on e.g. bradykinin, which is a vasodilator and also have other actions, could in theory make the two types of blockade clinically different. At present, the relative risk of precipitating renal failure by using the different compounds is unsettled. Thus in one case renal function deteriorated following both the ACE inhibitor enalapril and losartan [1]. In contrast, another case-report observed deterioration of renal function during enalapril treatment but no effect of subsequent losartan treatment [5]. Conversely, in a study comparing the usefulness of the ACE inhibitor captopril and losartan renography for detection of renovascular hypertension it was in a single case found that losartan but not captopril induced a fall in renal function in a kidney with more than 80% renal artery stenosis [6].

The pre-publication history for this paper can be accessed here: