Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used analgesics that have a high risk of renal injury, especially in susceptible populations such as the elderly, patients with chronic kidney disease (CKD), heart failure, or those on poly pharmacy. This commentary emphasizes the pathophysiological mechanisms of NSAID-induced kidney damage, including prostaglandin inhibition, renal vasoconstriction, and interstitial nephritis—and highlights recent evidence linking NSAIDs to acute kidney injury (AKI) and CKD progression. Despite relatively low incidence rates, the extensive use of NSAIDs increases the clinical burden of nephrotoxicity. Clinical challenges include delayed diagnosis due to modest symptomatology and under-recognition by both patients and healthcare providers. The article underscores the need for individualized NSAID prescribing patient education, informed consent, and enhanced regulatory oversight. It also explores safer pharmacological and non-pharmacological pain management alternatives, emerging nephron protective strategies, and the role of pharmacogenomics and early biomarkers in preventing NSAID-related renal damage. A multidisciplinary, patient-centered approach is advocated to optimize pain control while protecting kidney health.

NSAIDs, AKI, Renal Ischemia, Renal protection