ACE and ARB — reductions in GFR

Both angiotensin-converting enzyme inhibitor (ACEI) and angiotensin-II receptor blocker (ARB) therapy are associated with a reduction in proteinuria and slowing of the rate of progression of kidney failure.

ACEIs or ARBs are first-line therapy for hypertension, and preferred over other first-line therapies for people with kidney damage.1

When treatment is started, ACEI or ARB therapy can cause a temporary reduction in glomerular filtration rate (GFR).2

Monitor GFR within 2 months of starting therapy:

  • If GFR reduction is less than 25% and stabilises, ACEI or ARB therapy should continue
  • If GFR reduction is > 25% below the baseline value, stop ACEI or ARB therapy and consider referral to a nephrologist for further investigation

ACEI or ARB therapy can be safely prescribed at all stages of chronic kidney disease and should not be deliberately avoided just because GFR is reduced.

Combined therapy of ACEI and ARB is not recommended except with specialist advice.2 Recent studies in patients with diabetic nephropathy or at high risk for vascular events taking the combination have shown an increased risk of adverse effects like hyperkalaemia, acute kidney injury and hypotensive symptoms with little additional benefit in blood pressure control.3,4


It is recommended that kidney function and electrolytes be measured before starting either of these medicines and reviewed after 1–2 weeks.

Keep in mind the following:1,5

  • There is a significant risk of hyperkalaemia with ACEI or ARB use in people with kidney disease. Stop the ACEI or ARB if blood/serum potassium concentration is > 6 mmol/L and does not respond to dose reduction, diuretic therapy and dietary potassium restriction.
  • In patients with haemodynamically significant renal artery stenosis, ACEI or ARB therapy can cause further impairment of glomerular perfusion in the affected kidney, and precipitate acute deterioration in kidney function.
  • The 'triple whammy': take particular care in a patient with kidney disease treated with both an ACEI (or ARB) and a diuretic. Do not add an NSAID (including selective COX-2 inhibitors) to this combination as this can cause acute kidney failure.

'Triple whammy’ effect6

The 'triple whammy' effect occurs when a patient is given a combination of ACEI (or ARB), a diuretic and an NSAID. These agents, when prescribed together, have an additive detrimental effect on kidney function by reducing blood flow to the glomerulus and reducing GFR.

Block prostaglandin production, reduced blood flow to the glomerulus
Reduced blood flow to the glomerulus
Reduced glomerular filtration rate via efferent arteriole dilation
Single nephron

Effect of NSAIDs, diurectics and angiotensin inhibitors on a single nephron
Image from:

  1. Cardiovascular Writing Group. Therapeutic Guidelines: Cardiovascular. Version 6 ed. Melbourne: Therapeutic Guidelines Ltd, 2012.
  2. Kidney Health Australia. Chronic kidney disease (CKD) management in general practice. 2nd edition. 2012. (accessed 30 May 2013).
  3. Yusuf S, Teo KK, Pogue J, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008;358:1547–59. [PubMed]
  4. Fried LF, Emanuele N, Zhang JH, et al. Combined angiotensin inhibition for the treatment of diabetic nephropathy. N Engl J Med 2013;369:1892–903. [PubMed]
  5. Australian medicines handbook drug choice companion: aged care: Third Edition. Adelaide: Australian Medicines Handbook Ltd, 2010.
  6. Cupp M. The "Triple Whammy". Pharmacist's Letter 2013;29(4):290408 [Online]