Effect of IV magnesium supplementation in reducing adverse cisplatin associated kidney outcomes.

Abstract

12123 Background: Cisplatin is a commonly used chemotherapy agent that is associated with significant nephrotoxicity due to renal tubular cell injury. IV magnesium (mg) has emerged as a potential agent for preventing cisplatin-induced kidney injury. This study aims to explore the efficacy of IV mg in reducing cisplatin induced major adverse kidney events (MAKE). Methods: This is a retrospective observation cohort study of the TriNetX research network (with NLP) which included 105 Health care organizations (HCOs). Patients who received first dose of IV Cisplatin between 09/30/2004 to 09/30/2024 were included. Cohort further divided into two groups based on IV Mg supplementation during chemotherapy: IV Mg and Control groups. To mitigate potential confounding variables, we conducted 1:1 propensity score matching (PSM) that involved 42 variables covering demographics, comorbidities, medications, and laboratory results. The primary outcome of interest was MAKE, defined as stage 3 AKI, Dialysis or eGFR < 15 ml/min/1.73m2, Death at 30 days. Secondary outcomes were mortality and dialysis needing AKIs at 30 days. Adjusted hazard ratios (AHRs) with 95% CIs and P values were calculated using Cox proportional hazards regression models for all outcomes. The Kaplan-Meier method was used to estimate survival probabilities after PSM, considering 2-sided p < .05 as statistically significant. Sensitivity analyses with different observations and study window and subgroup analysis were done. Results: Our analysis consisted of 106,141 adults who received their first dose of IV Cisplatin. After excluding 519 patients with previous ESRD, 23,761(age 60.1+12.6, Male-51.8%, White-75.1%) were in IV Mg group(22.5%) and 81,861 (age 56.2+14.5, Male-58.5%, White-40.9%) in control group(77.5%). After PSM, each group had 20,647 participants. MAKE incidence was 586/20647(2.84%) in IV Mg group vs. 1934/20647(9.37%) in the control (aHR 0.28; 95% CI, 0.26-0.31). The mortality incidence was 274/20,647(1.33%) in the IV Mg group compared to 515/20,647 (2.49%) in the control group (aHR 0.53; 95% CI, 0.45-0.61). Dialysis needing AKIs were 27/20,647(0.13%) in IV Mg group vs. 102/20,647(0.49%) in control group (aHR 0.26; 95% CI, 0.17-0.40). Sensitivity analysis with 90 days observation window and last 5 years of study period (09/30/2019 to 09/30/2024) and different subgroup analysis showed consistent results. Conclusions: IV mg supplementation is associated with reduced MAKE and mortality in patients receiving cisplatin. Baseline characteristics of patients after propensity score matching. Characteristic IV Mg group Control Std Diff Demographic Age, mean 59.5(12.9) 59.1 (13.7) 0.035 Male, n (%) 10810 (52.36%) 10724 (51.94%) 0.008 White, n (%) 14834 (71.85%) 15095 (73.11%) 0.028 Hispanic, n (%) 1248 (6.04%) 1478 (7.16%) 0.045 Comorbidities, n (%) Malignant neoplasms of ill-defined, other secondary and unspecified sites 10789 (52.26%) 10700 (51.82%) 0.009 Hypertension 8408 (40.72%) 8402 (40.69%) 0.001 Malignant neoplasms of Head and Neck 4844 (23.46%) 4427 (21.44%) 0.0482 Hyperlipidemia 4801 (23.25%) 4670 (22.62%) 0.015 Nicotine dependence 4478 (21.69%) 4445 (21.53%) 0.004 Type 2 diabetes mellitus 3048 (14.76%) 3035 (14.7%) 0.002 Ischemic heart diseases 2554 (12.37%) 2534 (12.27%) 0.003 Chronic obstructive pulmonary disease 2403 (11.64%) 2292 (11.1%) 0.017 Cerebrovascular diseases 1038 (5.03%) 1043 (5.05%) 0.001 Chronic kidney disease 933 (4.52%) 893 (4.33%) 0.009 Heart failure 698 (3.38%) 726 (3.52%) 0.007 Medications, n (%) Beta-Blockers 6594 (31.94%) 6655 (32.23%) 0.006 Proton pump inhibitors 6018 (29.15%) 6111 (29.6%) 0.01 Statin 4911 (23.79%) 4949 (23.97%) 0.004 RAS Blockers 4739 (22.95%) 4664 (22.59%) 0.009 Diuretics 4475 (21.67%) 4666 (22.6%) 0.022 NSAIDS 4155 (20.12%) 4348 (21.06%) 0.023 Allopurinol 662 (3.21%) 776 (3.76%) 0.03 Gemcitabine 522 (2.53%) 465 (2.25%) 0.018 Methotrexate 448 (2.17%) 391 (1.89%) 0.02 PD-1/PDL-1 inhibitors 325 (1.57%) 314 (1.52%) 0.004 Doxorubicin 288 (1.4%) 304 (1.47%) 0.007 VEGF/VEGFR inhibitors 226 (1.1%) 208 (1.01%) 0.009 Zoledronic acid 203 (0.98%) 207 (1%) 0.002 Cyclophosphamide 159 (0.77%) 165 (0.8%) 0.003 Pemetrexed 111 (0.54%) 113 (0.55%) 0.001 Ifosfamide 21 (0.1%) 46 (0.22%) 0.03 Laboratory Blood Pressure, Systolic 125.8 (20.5) 125.3 (20.5) 0.025 BMI, mean (SD), kg/m2 27.6 (6.5) 27.2 (6.5) 0.059 >= 30 kg/m2, n (%) 5930 (28.72%) 5993 (29.03%) 0.007 Sodium, mean (SD), mmol/L 138.2 (3.2) 137.9 (3.5) 0.075 Potassium, mean (SD), mmol/L 4.2 (0.4) 4.1 (0.5) 0.09 Creatinine, mean (SD), mg/dL 0.87(1.42) 0.85 (0.35) 0.018 Hemoglobin A1c, mean (SD), % 6.5 (2.0) 6.4 (1.5) 0.102 Hemoglobin, mean (SD), g/dL 12.7(2.1) 12.4 (2.1) 0.163 < 10 g/dL, n (%) 4444 (21.52%) 4671 (22.62%) 0.027 Albumin, mean (SD), g/dL 3.9(0.6) 3.8 (0.6) 0.187 < 3 g/dL, n (%) 3175 (15.38%) 3413 (16.53%) 0.031 Magnesium, mean (SD), mg/dL 1.96 (0.25) 1.97 (0.29) 0.039 < 1.7 mg/dL, n (%) 3853 (18.66%) 4065 (19.69%) 0.026