Aim: To describe the prognostic value of three novel biomarkers for acute adverse kidney events compared with routine biological markers. Material & methods: We used high-end MS to quantify biomarkers predictive of acute kidney injury (AKI) and major adverse kidney events (MAKE) in 100 adult patients after open heart surgery (n = 100). Results: Early postoperatively measured LG3 (a C-terminal fragment of perlecan), LTBP2 (latent transforming growth factor binding protein-2), Cathepsin L as well as two other renal biomarkers (NGAL, Cystatin C) had greater predictive value for AKI (n = 23) and MAKE (n = 24) compared with creatinine, urea and urine output. Conclusions: LG3, LTBP2 and Cathepsin L deserve further exploration as biomarkers for the early identification of patients at risk of MAKE.