Can acute renal failure occur as a result of treatment with AE (angiotensin converting enzyme) inhi

Fråga: Can acute renal failure occur as a result of treatment with AE (angiotensin converting enzyme) inhibitors for hypertension?

Sammanfattning: "ARF is a known adverse effect of therapy with ACE inhibitors. In most cases, it is due to underlying renovascular pathology. This ""functional"" renal failure is reversible and is precipitated by hypotension, hypovolemia and hyponatremia. It may also occur in preexisting renal pathology, or as a result of a hypersensitivity reaction.

It is recommended that renal function should be assessed prior to and during treatment with ACE inhibitors. Use is cautioned in patients with generalized atherosclerosis, because of possible renal artery involvement."

Svar: Questions about renal insufficiency as a direct result of treatment with ACE inhibitors have previously been answered (1). Acute renal failure (ARF, which may represent one extreme of a spectrum of renal involvement) is said to occur almost exclusively in patients with compromised renal perfusion, as occurs with atheroma or fibrodysplaia of the renal arteries, or in low output cardiac failure. Such renovascular pathology has been suggested to account for up to 14.5 per cent of severe or resistant hypertension (2).

Because of the wide variation in extent of renal involvement, it has been difficult to assess the incidence of ARF that occurs with the use of ACE inhibitors, although it is relatively uncommon. In contrast, minor asymptomatic changes in serum creatinine are relatively common.

In such cases of compromised renal perfusion, ARF is usually reversible, and is a predictable consequence of ACE inhibition. With compromised renal perfusion, the kidney responds by releasing renin. This leads to an elevated angiotensin II level, which acts primarily to cause vasoconstriction of the renal efferent arterioles. This increases the hydrostatic pressure in the glomerular capillaries, and thus maintains an adequate glomerular filtration rate. Giving an ACE inhibitor to these patients, especially if there are additional renin requirements due to concomitant volume or sodium depletion (eg due to diuretic use), results in a loss of efferent vasoconstriction, and therefore greatly reduced glomerular filtration, leading to ARF. This "functional" ARF is reversible upon reducing the dose of ACE inhibitor, and does not acutely result in renal parenchymal damage, although animal studies have suggested that this may occur with repeated episodes of ARF (for review see 3).

ARF also occurs sporadically in the absence of renovascular disease. In some cases, this may be due to an acute allergic hypersensitivity reaction, as has been described for captopril (4). This is sometimes associated with systemic symptoms of fever, desquamative skin rash, Coomb´s positive haemolytic anaemia and plasma eosinophilia. Renal biopsy shows acute interstitial nephritis. This responds to drug withdrawal and treatment with prednisone.

Other cases of ARF have been described in hypertension due to pre-existing renal pathology such as nephrosclerosis, as described by Toto et al (5). In this study, reversible ARF occurred during hypotensive episodes in patients with diuretics and ACE inhibitors but not in patients treated with diuretics alone, thus demonstrating the importance of the renin-angiotensin system in protecting renal function.

Use of ACE inhibitors forms a significant proportion of cases of ARF. In a study of 530 consecutive patients admitted to hospital with ARF, 4 per cent were attributed to the use of ACE inhibitors, most of which resolved upon stopping the drug. Of these, 18/21 were subsequently shown to have significant renovascular pathology, and 2/21 had demonstrable renal pathology as assessed by biopsy.