Derivation and external validation of a simple risk score for predicting severe acute kidney injury after intravenous cisplatin: cohort study.

OBJECTIVE: To develop and externally validate a prediction model for severe cisplatin associated acute kidney injury (CP-AKI). DESIGN: Multicenter cohort study. SETTING: Six geographically diverse major academic cancer centers across the US. PARTICIPANTS: Adults (≥18 years) receiving their first dose of intravenous cisplatin, 2006-22. MAIN OUTCOME MEASURES: The primary outcome was CP-AKI, defined as a twofold or greater increase in serum creatinine or kidney replacement therapy within 14 days of a first dose of intravenous cisplatin. Independent predictors of CP-AKI were identified using a multivariable logistic regression model, which was developed in a derivation cohort and tested in an external validation cohort. For the primary model, continuous variables were examined using restricted cubic splines. A simple risk model was also generated by converting the odds ratios from the primary model into risk points. Finally, a multivariable Cox model was used to examine the association between severity of CP-AKI and 90 day survival. RESULTS: A total of 24 717 adults were included, with 11 766 in the derivation cohort (median age 59 (interquartile range (IQR) 50-67)) and 12 951 in the validation cohort (median age 60 (IQR 50-67)). The incidence of CP-AKI was 5.2% (608/11 766) in the derivation cohort and 3.3% (421/12 951) in the validation cohort. Each of the following factors were independently associated with CP-AKI in the derivation cohort: age, hypertension, diabetes mellitus, serum creatinine level, hemoglobin level, white blood cell count, platelet count, serum albumin level, serum magnesium level, and cisplatin dose. A simple risk score consisting of nine covariates was shown to predict a higher risk of CP-AKI in a monotonic fashion in both the derivation cohort and the validation cohort. Compared with patients in the lowest risk category, those in the highest risk category showed a 24.00-fold (95% confidence interval (CI) 13.49-fold to 42.78-fold) higher odds of CP-AKI in the derivation cohort and a 17.87-fold (10.56-fold to 29.60-fold) higher odds in the validation cohort. The primary model had a C statistic of 0.75 and showed better discrimination for CP-AKI than previously published models, the C statistics for which ranged from 0.60 to 0.68 (DeLong P<0.001 for each comparison). Greater severity of CP-AKI was monotonically associated with shorter 90 day survival (adjusted hazard ratio 4.63 (95% CI 3.56 to 6.02) for stage 3 CP-AKI versus no CP-AKI). CONCLUSION: This study found that a simple risk score based on readily available variables from patients receiving intravenous cisplatin could predict the risk of severe CP-AKI, the occurrence of which is strongly associated with death.

High-dose IV magnesium in mesothelioma patients receiving surgery with hyperthermic intraoperative cisplatin: Pilot studies and design of a phase II randomized clinical trial.

INTRODUCTION: Hyperthermic intraoperative cisplatin (HIOC) is associated with acute kidney injury (AKI). Administration of high-dose magnesium attenuates cisplatin-induced AKI (CP-AKI) in animal models but has not been rigorously examined in humans. METHODS: We tested the feasibility and safety of different doses of magnesium in mesothelioma patients receiving HIOC. In Pilot Study 1, we administered a 36-h continuous infusion of magnesium at 0.5 g/h, targeting serum magnesium levels between 3 and 4.8 mg/dL. In Pilot Study 2A, we administered a 6 g bolus followed by an infusion starting at 2 g/h, titrated to achieve levels between 4 and 6 mg/dL. We eliminated the bolus in Pilot Study 2B. RESULTS: In Pilot Study 1, all five patients enrolled completed the study; however, median postoperative Mg levels were only 2.4 mg/dL. In Pilot Study 2A, two of four patients (50%) were withdrawn due to bradycardia during the bolus. In Pilot Study 2B, two patients completed the study whereas two developed postoperative bradycardia attributed to the magnesium. CONCLUSIONS: A 0.5 g/h infusion for 36 h did not achieve therapeutic magnesium levels, while an infusion at 2 g/h was associated with bradycardia. These studies informed the design of a randomized clinical trial testing whether intravenously Mg attenuates HIOC-associated AKI.