Angiotensin is a short peptide hormone that causes constriction of the efferent arteriole at the glomerulus, leading to increased glomerular filtration pressure. This can maintain glomerular filtration when renal blood flow drops (low blood pressure, renal artery stenosis), but drugs may paralyse this reflex. Angiotensin also has direct effects on many other cells, including the podocyte, and it is likely that some of its effects depend on these other actions too.
Angiotensin converting enzyme inhibitors (ACE inhibitors)
Excellent agents for hypertension, including in renal disease, but particularly for proteinuria-associated renal disease:
- Effective with a low incidence of adverse symptoms
- Reduce proteinuria, regardless of cause
- Proven protective effect on renal function in renal disease with proteinuria
- Hypotensive effect potentiated by sodium restriction and diuretics
Most evidence for these benefits has come from trials in which ACE inhibitors were used at maximum or near-maximum doses.
1. Cause a dry cough in some recipients
2. Can cause hyperkalaemia; especially
- in combination with other drugs (e.g. potassium-sparing diuretics)
- in patients with renal impairment
3. Cause a variable drop in GFR in anyone, but can can cause a marked drop in the presence of renal artery stenosis
- if renal artery stenosis is bilateral or to a single kidney
- more likely if combined with diuretic therapy
4. Predispose to acute kidney injury if patient becomes dehydrated or infected, or cardiac output or blood pressure drop.
Choice of drug
Some are effective when given once daily. Some may be less likely to cause first-dose hypotension. However most effects are shared by all drugs in the class. Captopril was the prototype, but it needs to be given two or three times daily and has some additional side effects.
Angiotensin II receptor type I antagonists (ARBs)
Angiotensin receptor blockers (ARBs) have similar effects and side-effects to ACE inhibitors, except that they do not cause cough. They are first-choice alternatives if ACE inhibitor-induced cough occurs, but are otherwise probably broadly comparable. ACE inhibitors and ARBs have rarely been directly compared.