Are Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) contraindicated in Acute Kidney Injury (AKI)?

From the Guidelines

NSAIDs are generally contraindicated in acute kidney injury (AKI) due to their potential to worsen kidney function by inhibiting prostaglandin synthesis, reducing renal blood flow, and causing direct tubular toxicity and interstitial nephritis. According to the most recent and highest quality study, patients with cirrhosis and ascites who develop AKI should have all potentially nephrotoxic drugs, including NSAIDs, withdrawn as soon as possible 1. This is because NSAIDs can further compromise already injured kidneys, leading to a decline in kidney function and potentially worsening morbidity and mortality.

Key Considerations

• NSAIDs, including ibuprofen, naproxen, celecoxib, diclofenac, and ketorolac, should be avoided in patients with AKI.
• Alternative pain management options, such as acetaminophen for mild pain or carefully dosed opioids for more severe pain, should be used under close medical supervision.
• Kidney function should be monitored regularly in patients with AKI, and medication choices should be reassessed as kidney function improves.
• The use of NSAIDs in patients with AKI can lead to direct tubular toxicity and interstitial nephritis, further compromising kidney function.

Management of AKI

• Patients with cirrhosis and ascites who develop AKI should be managed according to the International Club of Ascites—AKI (ICA-AKI) classification, which combines Kidney Disease Improving Global Outcomes (KDIGO) criteria and conventional criteria 1.
• The management algorithm includes reviewing the drug chart, reducing or withdrawing diuretic therapy, withdrawing all potentially nephrotoxic drugs, including NSAIDs, and plasma volume expansion in patients with clinically suspected hypovolemia.
• Further management depends on the progression of the AKI stage, with patients who do not respond to initial treatment requiring more intensive management, including the use of vasoconstrictors and albumin.

From the Research

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and Acute Kidney Injury (AKI)

• The use of NSAIDs is typically avoided in patients at risk for kidney disease, as they may increase the risk of AKI, especially in patients with older age, diabetes mellitus, lower eGFR, diuretic use, and cardiovascular disease 2.
• The risk of AKI associated with NSAIDs is higher with longer courses and may affect the progression of AKI 2.
• Regular NSAID use could be associated with an increased incidence of chronic kidney disease (CKD), but the relation between NSAID use and CKD progression is less clear 2.
• Disruption in prostaglandins production due to NSAIDs use may result in ischemic AKI in at-risk patients, and other complications include hyperkalemia, hyponatremia, nephrotic syndrome, acute interstitial nephritis, and CKD progression 3.

Contraindication of NSAIDs in AKI

• AKI from NSAIDs is usually reversible with favorable prognosis after discontinuation of NSAIDs, emphasizing the importance of avoidance of NSAIDs exposure, especially among high-risk patients 3.
• The association between AKI and use of NSAIDs is well established, and individual NSAIDs have been found to have a statistically significant elevated AKI risk, with pooled risk ratios ranging from 1.58 to 2.11 4.
• Short-term NSAID use may pose a risk in hospitalized patients, particularly those with preexisting renal impairment, with an increased risk of AKI (hazard ratio: 1.38) 5.

Comparison with Other Analgesics

• Acetaminophen is considered safer than NSAIDs for the kidneys, with scarce association between acetaminophen administration and AKI development, although regular acetaminophen use should be reassessed in patients with uncontrolled hypertension 2, 6.