Abstract: We identified 26 studies (8835 participants). Risk of bias was high in 17, unclear in 6and low in three studies. There was high risk of attrition bias in six studies. Only two studies measured AKI. The use of NSAIDs had uncertain effects on the incidence of AKI compared to placebo (7066 participants: RR 1.79, 95% CI 0.40 to 7.96; I2 = 59%; very low certainty evidence). One study was stopped early by the data monitoring committee due to increased rates of AKI in the NSAID group. Moreover, both of these studies were examining NSAIDs for indications other than analgesia and therefore utilised relatively low doses. Compared to placebo, NSAIDs may slightly increase serum SCr (15 studies, 794 participants: MD 3.23 μmol/L, 95% CI -0.80 to 7.26; I2 = 63%; low certainty evidence). Studies displayed moderate to high heterogeneity and had multiple exclusion criteria including age and so were not representative of patients undergoing surgery. Three of these studies excluded patients if their creatinine rose post-operatively. NSAIDs may make little or no difference to post-operative urine output compared to placebo (6 studies, 149 participants: SMD -0.02, 95% CI -0.31 to 0.27). No reliable conclusions could be drawn from these studies due to the differing units of measurements and measurement time points. It is uncertain whether NSAIDs leads to the need for RRT because the certainty of this evidence is very low (2 studies, 7056 participants: RR 1.57, 95% CI 0.49 to 5.07; I2 = 26%); there were few events and the results were inconsistent. It is uncertain whether NSAIDs lead to more deaths (2 studies, 312 participants: RR 1.44, 95% CI 0.19 to 11.12; I2 = 38%) or increased the length of hospital stay (3 studies, 410 participants: MD 0.12 days, 95% CI -0.48 to 0.72; I2 = 24%). Overall NSAIDs had uncertain effects on the risk of post-operative AKI, may slightly increase post-operative SCr, and it is uncertain whether NSAIDs lead to the need for RRT, death or increases the length of hospital stay. The available data therefore does not confirm the safety of NSAIDs in patients undergoing surgery. Further larger studies using the Kidney Disease Improving Global Outcomes definition for AKI including patients with co-morbidities are required to confirm these findings. .

Plain-language summary: We identified 26 studies studying 8835 participants. Risk of bias was high in 17, unclear in six studies and low in three studies. The use NSAIDs had uncertain effects on the incidence of AKI compared to placebo. Quality of evidence was very low due to inconsistencies between the two studies. One study was stopped early by the data monitoring committee due to increased rates of AKI in the NSAID group and both of these studies examined much lower doses of NSAIDs than would usually be used for pain relief. NSAIDs may slightly increase serum creatinine (a marker of kidney function which rises in kidney failure) compared with placebo. Quality of evidence was low. These studies only included fit, healthy patients. No reliable conclusions could be drawn from the studies examining urine output due to the different methods of measuring this. It is uncertain whether the use of NSAIDs leads to an increased need for renal replacement therapy (dialysis), more deaths, or increased length of hospital stay. NSAIDs have uncertain effects on the rates of AKI when used in patients with normal kidney function following surgery. It is uncertain whether NSAIDs increase the need for dialysis. The available data therefore does not confirm the safety of NSAIDs in patients undergoing surgery. Further studies including patients with other health problems are required.