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MHRA warns that NSAIDs can cause severe renal damage in patients at increased risk

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Medicines Management provides essential evidence-based information on medicines and prescribing for nurse prescribers and those involved in administering medicines

Key words: Prescribing information, NSAIDS, Renal

Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most widely used classes of medicines. In England some 7.9 million and 4.6 million prescriptions were issued for diclofenac and ibuprofen respectively in 2006 – around 71% of NSAID prescriptions. About 5% of NSAID prescriptions are for Cox-2 inhibitors (such as, celecoxib and etoricoxib), which inhibit cyclo-oxygenase-2 (Clinical Knowledge Summaries, 2009).

Safety issues

While NSAIDs are generally well tolerated, the Medicines and Healthcare products Regulatory Agency has reminded clinicians to exercise caution in prescribing them to patients with established or risk of renal impairment.

The reminder was issued because the agency continues ‘to receive case reports of renal failure in NSAID users’. It highlights that several groups of vulnerable patients, particularly older people, might be especially prone to this adverse event.

Risk of renal failure

Although renal failure associated with NSAIDs is relatively rare, Delmas (1995) suggested they account for up to 16% of cases of drug-induced acute renal failure. The MHRA (2009) cited a case-control study that compared 103 cases of idiopathic acute renal failure and 5,000 age- and sex-matched controls. Current users of NSAIDs were around three times more likely to develop acute renal failure than controls – a relative risk of 3.2. The risk declined after discontinuing NSAIDs.

During NSAID treatment, the risk increased in patients with a history of heart failure, hypertension or diabetes, and those reporting hospitalisations and consultant visits in the previous year. Concomitant use of NSAIDs with diuretics or calcium channel blockers also increased the risk of acute renal failure.

NSAIDs alleviate pain and fever by reducing prostaglandin production. Specifically, they block the enzyme cyclo-oxygenase, which synthesizes prostaglandins from arachidonic acid, a fatty acid found in cell membranes. Conventional NSAIDs block both types of cyclo-oxygenase (Cox) isozyme for prostaglandin production. Cox-2 inhibitors block only one isozyme.

Prostaglandins have numerous important roles. For example, apart from activating inflammation, they can induce vasodilatation, which increases renal blood flow. The MHRA says NSAIDs can reduce renal blood flow, which accounts for most of the renal adverse events associated with the drugs. NSAIDs may also directly damage the kidneys.

The agency says NSAIDs can produce acute renal failure by, for example, inducing acute tubular necrosis and acute interstitial nephritis (inflamed tubules). Rarer causes of acute renal failure include acute papillary necrosis (death of the renal papilla, where the pyramids empty urine into the renal pelvis) and renal vasculitis. In general, such changes are reversible when the NSAID is withdrawn. However, Delmas (1995) says interstitial nephritis and papillary necrosis ‘are more often irreversible’ than the other forms of NSAID-related renal damage.

The MHRA says clinicians should consider any concomitant diseases, conditions and medications before prescribing NSAIDs. It warns that patients with conditions that cause renal hypoperfusion – such as hypovolaemia, congestive heart failure, liver cirrhosis or multiple myeloma – are at particular risk of renal problems when taking NSAIDs.

Other risk factors include concomitant use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin-II receptors antagonists, and diuretics. All these can have negative effects on the kidney.

Nurses’ role

Nurses should ensure that they are familiar with the prescribing information for NSAIDs, which includes warnings about renal impairment and kidney failure. The MHRA recommends that patients at risk of renal impairment or kidney failure, particularly older people, should not use NSAIDs if possible.

If NSAIDs are necessary, patients should receive the lowest effective dose for the shortest possible duration. Furthermore, the MHRA advises monitoring the patient’s renal function ‘carefully’ during NSAID treatment.

Mark Greener, BSc, is a freelance medical writer

Key points

  • NSAIDs occasionally precipitate renal failure. They are responsible for around one in seven cases of drug-induced acute renal failure.
  • Healthcare professionals should consider other concomitant diseases, conditions or medicines that may precipitate reduced renal function when prescribing NSAIDs.
  • Older people and patients with hypovolaemia, congestive heart failure, liver cirrhosis, or multiple myeloma may be at increased risk of renal damage during NSAID treatment.
  • Concomitant ACE inhibitors, angiotensin II receptor antagonists and diuretics increase the risk of acute renal failure.
  • Patients at risk of renal impairment or failure should avoid NSAIDs where possible. If NSAIDs are necessary, patients should receive the lowest effective dose for the shortest possible duration and undergo renal function monitoring 
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