What kidney and liver lab tests are required before prescribing Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?

From the Guidelines

Before prescribing Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), baseline kidney and liver function tests should be performed, including serum creatinine, blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), and liver enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and bilirubin. These tests are essential because NSAIDs can potentially cause kidney injury by reducing renal blood flow through inhibition of prostaglandin synthesis, which normally helps maintain kidney perfusion 1. NSAIDs may also cause hepatotoxicity, particularly with long-term use, with some NSAIDs, such as sulindac and diclofenac, showing higher rates of hepatic injury and transaminase elevation more than three times the upper limit of normal compared with placebo 1.

Key Lab Tests

• Serum creatinine
• Blood urea nitrogen (BUN)
• Estimated glomerular filtration rate (eGFR)
• Liver enzymes:
  • Alanine aminotransferase (ALT)
  • Aspartate aminotransferase (AST)
  • Alkaline phosphatase (ALP)
  • Bilirubin According to the 2011 American College of Rheumatology recommendations, measurement of serum creatinine, urinalysis, complete blood cell count, and liver enzymes was recommended prior to or soon after the initiation of treatment with routine NSAIDs 1.

Monitoring Frequency

For patients on chronic NSAID therapy, these tests should be repeated periodically, approximately twice yearly for patients receiving chronic daily NSAIDs and approximately once yearly for patients receiving NSAIDs routinely 1. Electrolytes should also be checked, as NSAIDs can cause sodium retention and potassium abnormalities. If abnormalities are detected, dose reduction, medication discontinuation, or switching to a different pain management strategy may be necessary. Patients with pre-existing kidney or liver impairment are at higher risk for adverse effects and may require dose adjustments or alternative medications.

From the FDA Drug Label

Aspirin Clinical Impact:Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone ACE Inhibitors, Angiotensin Receptor Blockers, and Beta-Blockers Clinical Impact:· NSAIDs may diminish the antihypertensive effect of ACE inhibitors, ARBs, or beta-blockers (including propranolol) · In patients who are elderly, volume-depleted (including those on diuretic therapy), or have renal impairment, co-administration of an NSAID with ACE inhibitors or ARBs may result in deterioration of renal function, including possible acute renal failure. Diuretics Clinical Impact:Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients. Lithium Clinical Impact:NSAIDs have produced elevations in plasma lithium levels and reductions in renal lithium clearance Cyclosporine Clinical Impact:Concomitant use of celecoxib capsules and cyclosporine may increase cyclosporine’s nephrotoxicity Pemetrexed Clinical Impact: Concomitant use of celecoxib capsules and pemetrexed may increase the risk of pemetrexed-associated myelosuppression, renal, and GI toxicity

To prescribe NSAIDs, the following kidney and liver lab tests should be considered:

• Renal function tests:
  • Creatinine clearance
  • Serum creatinine
• Liver function tests:
  • No specific liver function tests are mentioned in the context of NSAID prescription, but it is essential to monitor liver enzymes in patients with pre-existing liver disease. In patients with renal impairment, it is crucial to:
• Monitor serum creatinine and creatinine clearance before and during NSAID treatment.
• Assess renal function at the beginning of the concomitant treatment and periodically thereafter. In patients taking lithium, digoxin, or cyclosporine, it is essential to monitor:
• Lithium levels for signs of toxicity
• Digoxin levels for signs of toxicity
• Renal function for signs of worsening renal function 2

From the Research

Kidney Lab Tests for NSAIDs Prescription

• Estimated Glomerular Filtration Rate (eGFR) is a crucial test to assess kidney function before prescribing NSAIDs, as it helps identify patients with impaired renal function who may be at risk of NSAID-induced nephrotoxicity 3, 4.
• Serum creatinine levels can also be used to monitor kidney function in patients taking NSAIDs, as elevated levels may indicate impaired renal function 5, 6.
• Creatinine clearance can be estimated using a standard formula that takes into account age, sex, and weight, and can be used to assess renal function in patients taking NSAIDs 6.

Liver Lab Tests for NSAIDs Prescription

• There is limited evidence on the specific liver lab tests required before prescribing NSAIDs, as the primary concern with NSAID use is nephrotoxicity rather than hepatotoxicity.
• However, patients with pre-existing liver disease or those taking other medications that may affect liver function should be monitored closely for potential interactions or adverse effects 6, 7.

Considerations for NSAIDs Prescription

• Patients with chronic kidney disease (CKD) or impaired renal function should be prescribed NSAIDs with caution, and alternative treatments should be considered whenever possible 3, 4.
• The half-life of the NSAID should be taken into account, as longer-acting NSAIDs may be more likely to cause renal impairment 6, 7.
• Patients should be monitored regularly for signs of renal impairment, including changes in serum creatinine levels or eGFR, and NSAID use should be adjusted or discontinued as needed 3, 4.