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In Clinical Decision Support System (CDSS), relevance of alerts is essential to limit alert fatigue and risk of overriding relevant alerts by health professionals. Detection of acute kidney injury (AKI) situations is of great importance in clinical practice and could improve quality of care. Nevertheless, to our knowledge, no explicit rule has been created to detect AKI situations in CDSS. The objective of the study was to implement an AKI detection rule based on KDIGO criteria in a CDSS and to optimize this rule to increase its relevance in clinical pharmacy use. Two explicit rules were implemented in a CDSS (basic AKI rule and improved AKI rule), based on KDIGO criteria. Only the improved rule was optimized by a group of experts during the two-month study period. The CDSS provided 1,125 alerts on AKI situations (i.e. 643 were triggered for the basic AKI rule and 482 for the improved AKI rule). As the study proceeds, the pharmaceutically and medically relevance of alerts from the improved AKI rule increased. A ten-fold increase was shown for the improved AKI rule compared to the basic AKI rule. The study highlights the usefulness of a multidisciplinary review to enhance explicit rules integrated in CDSS. The improved AKI is able to detect AKI situations and can improve workflow of health professionals.