INTRODUCTION: In patients who receive treatment for cancer, acute kidney injury (AKI) is arguably one of the most dangerous toxicities that results from cisplatin (CP), a chemotherapeutic agent. While AKI is a common occurrence amongst people who receive cisplatin (CP-AKI), the current risk assessment, intervention methods and understanding the role of magnesium in AKI, are either limited or understudied. OBJECTIVES: We aimed to build on previous CP-AKI risk prediction models, and establish a relationship between serum magnesium levels and AKI. Additionally, we used a feasibility study to test if intravenous magnesium sulfate in patients receiving intraoperative chemotherapy with cisplatin (HIOCC) for malignant mesothelioma can attenuate CP-AKI. This feasibility study was also used to determine a proper dosing regimen to achieve serum magnesium levels of 3 - 4.8 mg/dl.
METHODS: We defined acute kidney injury as a 1.5-fold increase in serum creatine, or use of renal replacement therapy (RRT). Using clinical and demographic information from Memorial Sloan Kettering’s database, we conducted multivariable and univariable regression was used to identify the most significant demographic and clinical lab values. Using the information from the statistical analysis we built on previous risk prediction models for cisplatin associated kidney injury. Using the same statistical analysis, we further explored the relationship between serum magnesium values and AKI. In the feasibility study, we recruited patients from Brigham and Woman’s hospital who were receiving HIOCC treatment for mesothelioma. They received an infusion of intravenous magnesium sulfate during surgery. Serum magnesium levels were measured pre-operatively and post-operatively along with serum creatinine values. These were used to obtain pharmacokinetic information to further adjust the infusion rate in patients, lab values were also used to identify any AKI.
CONCLUSION: A score-based model created using patient’s age, serum magnesium, albumin, hemoglobin, platelets, cisplatin dose and hypertension is predictive of cisplatin associated acute kidney injury. The feasibility study allowed us to inform phase 2 of an upcoming feasibility study that will include a bolus of 6g Mg/hr and an infusion of 2 g/hr after the bolus. This will work to increase the serum magnesium levels to the therapeutic range.
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/46322 |
| Date | 09 June 2023 |
| Creators | Seitter, Robert Henry |
| Contributors | McKnight, C. James, Gupta, Shruti |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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