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Though debated, the use of non-steroidal anti-inflammatory drugs in pain management could be associated with kidney injury, particularly in prolonged and high dose exposures. Therefore other supporting measures are needed to support or rule out nephrotoxicity. This mini review summaries available literature in the field. Various studies were reviewed and the weight of argument in support of refusal of NSAIDs nephrotoxicity and it showed no convincing evidence of the nephrotoxicity of NSAIDs except in acute interstitial nephritis. The risk of developing, and progression of CKD is also assessed but a definitive conclusion seem difficult to make even with higher doses and in prolonged exposures. While the argument ranges on, and in the interim assuming the nephrotoxicity of NSAIDs, the inclusion of some inflammatory markers that are known to be elevated or depressed in kidney disease could be of significant value in determining the true nephrotoxicity profile of NSAIDs in health, and perhaps in CKD. These markers may also be of value in the monitoring and prognostication of illnesses associated with NSAIDs use.