ACE inhibitors and raised creatinine in chronic kidney disease (CKD)

Last edited 11/2022 and last reviewed 07/2023

• BHS guidelines advise that ACEIs and ARBs be used with caution and under specialist advice in the presence of "renal impairment"
  
  
• previous NICE guidance advised that ACEI (or ARBs) should be initiated under specialist supervision in patients with plasma creatinine concentration above 150 µmol/L - however this is not included in the current guideline (2)
  
  
• there is a risk that these drugs will precipitate acute renal failure as a result of unrecognised bilateral critical renal vascular disease, by interrupting the intrarenal production of angiotensin II that normally maintains GFR in the presence of reduced renal perfusion
  
  
• even in the absence of atherosclerotic renal artery stenosis, antihypertensive drugs can cause reduction in GFR, by reducing renal perfusion; this is particularly likely in the presence of kidney disease, affecting autoregulation of renal blood flow
  
  
• at what level of deterioration in GFR or creatinine concentration rise should specialist advice be sought:
  • it has been recommended that discussion with a specialist if a patient's serum creatinine concentration rises by 30% or whose estimated GFR falls by 20% as an apparent consequence of ACEI/ARB use (1)
  • stop renin-angiotensin system antagonists if the serum potassium concentration increases to 6.0 mmol/litre or more and other drugs known to promote hyperkalaemia have been discontinued
  • following the introduction or dose increase of renin-angiotensin system antagonists, do not modify the dose if either the GFR decrease from pretreatment baseline is less than 25% or the serum creatinine increase from baseline is less than 30%
  • if there is a decrease in eGFR or increase in serum creatinine after starting or increasing the dose of renin-angiotensin system antagonists, but it is less than 25% (eGFR) or 30% (serum creatinine) of baseline, repeat the test in 1-2 weeks. Do not modify the renin-angiotensin system antagonist dose if the change in eGFR is less than 25% or the change in serum creatinine is less than 30%
  • If the eGFR change is 25% or more, or the change in serum creatinine is 30% or more:
    • investigate other causes of a deterioration in renal function, such as volume depletion or concurrent medication (for example, NSAIDs)
    • if no other cause for the deterioration in renal function is found, stop the renin-angiotensin system antagonist or reduce the dose to a previously tolerated lower dose, and add an alternative antihypertensive medication if required
      
      
• study evidence showed that among patients with advanced and progressive chronic kidney disease, the discontinuation of RAS inhibitors was not associated with a significant between-group difference in the long-term rate of decrease in the eGFR (3)

Reference:

1. The Renal Association (May 2006).UK CKD Guidelines
2. NICE (August 2021). Chronic kidney disease: assessment and management
3. Bhandari S et al. Renin-Angiotensin System Inhibition in Advanced Chronic Kidney Disease. NEJM November 3, 2022; DOI: 10.1056/NEJMoa2210639