NSAID use in patients who have an increased risk of nephrotoxicity
Dreischulte, 2015Gooch, 2007Kidney Disease Improving Global Outcomes (KDIGO), 2013Kuo, 2010Lapi, 2013Moller, 2015Nderitu, 2013Ungprasert, 2015Wei, 2013
Patient-specific risk factors for increased nephrotoxicity with NSAID use are outlined in Patient-specific risk factors for NSAID-induced acute kidney injury.
[NB1]
Patient-specific risk factors for NSAID-induced acute kidney injury include:
- pre-existing kidney impairment
- volume depletion (eg dehydration, sepsis) or effective arterial volume depletion (eg due to heart failure, cirrhosis, nephrotic syndrome)
- concurrent treatment with an ACEI, ARB, diuretic or nephrotoxin (eg aminoglycoside, contrast agent)
- older age.
ACEI = angiotensin converting enzyme inhibitor; ARB = angiotensin II receptor blocker; NSAID = nonsteroidal anti-inflammatory drug
NB1: The risk of acute kidney injury is cumulative—for example, the risk is significantly increased if an NSAID is co-administered with an ACEI plus a diuretic, or if an older patient taking an NSAID develops an acute illness associated with dehydration.
Avoid NSAIDs in patients with:
- a glomerular filtration rate (GFR) less than 30 mL/minute
- a GFR of 30 to 60 mL/minute if use will be long-term unless no alternative treatment is available and the patient has no other risk factors for acute kidney injury
- a GFR of 30 to 60 mL/minute who have a serious illness associated with risk of acute kidney injury—an NSAID can be restarted once the serious illness resolves
- a GFR less than 80 mL/minute who have postoperative or posttraumatic haemodynamic instability, or who are at risk of haemodynamic instability.
If treatment with an NSAID is being considered for a patient with other risk factor(s) for NSAID-induced acute kidney injury (including chronic kidney disease), weigh the potential benefits of the NSAID against its potential harms, noting that the likelihood of acute kidney injury is increased by the presence of more than one risk factor. For example, NSAIDs should be used with caution in patients with mild kidney impairment (GFR 60 to 90 mL/minute) who have other risk factors for acute kidney injury.
If an NSAID is used, use the minimum effective dose. NSAIDs with a short half-life are preferred. With the exception of modified-release preparations, NSAIDs that require more frequent daily dosing generally have a shorter half-life. All NSAIDs can cause acute and chronic kidney impairment, although the risk is thought to be lowest with celecoxib.
Check kidney function and blood pressure early after starting the NSAID to detect any acute change, and monitor closely if use is ongoing for patients with moderate kidney impairment (GFR 30 to 60 mL/min). Periodic monitoring is adequate for patients with other risk factor(s) for NSAID-induced acute kidney injury (eg mild kidney impairment, older age). Withhold the NSAID during any serious illness associated with risk of acute kidney injury.
The considerations for NSAID use in people with chronic kidney disease are outlined in NSAID use in patients with chronic kidney disease.
The use of NSAIDs in patients with chronic kidney disease requires particular consideration for 3 reasons:
- NSAIDs can cause an acute reduction in renal perfusion and GFR, which can lead to a reversible reduction in kidney function, hyperkalaemia, or acute ischaemic kidney injury. This risk is significantly increased in patients concurrently taking an ACEI, ARB or diuretic
- NSAIDs can increase blood pressure in patients with hypertension, a common comorbidity in patients with chronic kidney disease
- long-term use of NSAIDs can increase the rate of progression of chronic kidney disease when used at higher doses or in patients with more severe chronic kidney disease; however, observational data in patients with mild to moderate chronic kidney disease taking standard doses of NSAIDs have been reassuring, with no evidence of a detrimental effect on kidney function over time.