Magnesium prophylaxis for prevention of cisplatin induced nephrotoxicity

Statistical analysis

Categorical variables were summarized using frequencies and percentages, while continuous variables were summarized using means and standard deviations or medians and interquartile ranges, as appropriate. Linear mixed effects models were used to assess the association between IV magnesium prophylaxis and change in serum creatinine and creatinine clearance, adjusting for cycle, day (continuous), sex, and baseline creatinine clearance, with a random intercept for each patient (MRN). P values less than 0.05 were considered statistically significant. All analyses were performed using R version 4.2.2.

Results

Demographics

Patient demographics are summarized in Table 1 by sex.

Table 1: Baseline demographics of patients receiving cisplatin chemotherapy

Characteristic	Female N = 281	Male N = 601	Overall N = 881
Age	72 (63, 77)	54 (36, 69)	63 (42, 73)
Race
White	27 (96%)	57 (95%)	84 (95%)
Black	1 (3.6%)	1 (1.7%)	2 (2.3%)
American Indian or Alaskan Native	0 (0%)	1 (1.7%)	1 (1.1%)
Asian	0 (0%)	1 (1.7%)	1 (1.1%)
Ethnicity
Hispanic/Latino	3 (11%)	4 (6.7%)	7 (8.0%)
Not Hispanic or Latino	25 (89%)	56 (93%)	81 (92%)
Baseline Serum Creatinine (mg/dL)	0.72 (0.57, 0.85)	0.85 (0.72, 1.02)	0.81 (0.70, 1.00)
Baseline Creatinine Clearance (mL/min)	88 (65, 118)	99 (73, 127)	93 (68, 126)
1 Median (Q1, Q3); n (%)

IV Magnesium Prophylaxis and Nephrotoxicity

Descriptive statistics

Table 2 summarizes the number of measurements with or without IV Magnesium Prophylaxis at each cycle and day.

Table 2: Number of measurements with or without IV Magnesium Prophylaxis at each cycle and day.

Cycle	Day	Mg-No	Mg-Yes	Mg-NA
1	1	85	1	1
1	2	31	1	0
1	3	30	1	0
1	4	29	1	0
1	5	28	2	0
1	8	41	1	0
1	15	3	2	0
1	22	0	1	0
1	29	1	0	0
2	1	61	7	0
2	2	23	0	0
2	3	22	1	0
2	4	17	6	0
2	5	22	1	0
2	8	35	0	0
3	1	42	15	0
3	2	16	3	0
3	3	18	2	0
3	4	11	8	0
3	5	16	3	0
3	8	26	4	0
4	1	3	0	0
4	8	1	0	0
5	1	2	0	0
6	1	2	0	0

Figure 1 and Figure 2 show the change in serum creatinine and creatinine clearance over time by sex, cycle, and IV magnesium prophylaxis status. Each point represents an individual measurement, with a dashed line at y=0 indicating no change from baseline.

• It appears that male patients are doing better than females in terms of change in serum creatinine and creatinine clearance, especially in the first cycle.

Figure 1: Percent change in serum creatinine over time by sex, cycle, and IV magnesium prophylaxis status.

Figure 2: Change in creatinine clearance over time by sex, cycle, and IV magnesium prophylaxis status.

Longitudinal modeling

Table 3 and Table 4 show the results of linear mixed effects models assessing the association between IV magnesium prophylaxis and change in serum creatinine and creatinine clearance, respectively, adjusting for cycle, day (continuous), sex, and baseline creatinine clearance, with a random intercept for each patient (MRN).

Table 3: Linear mixed effects model for change in serum creatinine.

Variable1	Beta	95% CI	p-value
mg_iv			0.6
No	—	—
Yes	1.7	-5.2, 8.5
Cycle			0.2
1	—	—
2	3.1	-1.1, 7.4
3	3.7	-1.1, 8.5
Day	0.12	-0.53, 0.77	0.7
Sex			0.009
Female	—	—
Male	-13	-24, -3.3
Baseline Creatinine Clearance (mL/min)	0.19	0.08, 0.30	<0.001
1 Linear mixed effects model with random intercept for each patient (MRN).
Abbreviation: CI = Confidence Interval

Table 4: Linear mixed effects model for change in creatinine clearance.

Variable1	Beta	95% CI	p-value
mg_iv			0.7
No	—	—
Yes	0.73	-3.5, 5.0
Cycle			0.003
1	—	—
2	-2.3	-5.0, 0.32
3	-5.1	-8.1, -2.2
Day	-0.25	-0.66, 0.15	0.2
Sex			0.007
Female	—	—
Male	13	3.6, 23
Baseline Creatinine Clearance (mL/min)	-0.25	-0.35, -0.15	<0.001
1 Linear mixed effects model with random intercept for each patient (MRN).
Abbreviation: CI = Confidence Interval

• The effect of IV magnesium prophylaxis is not statistically significant;
• Cycle 2 and Cycle 3 are associated with a significant increase in serum creatinine and decrease in creatinine clearance compared to Cycle 1;
• Males have a significantly smaller increase in serum creatinine and smaller decrease in creatinine clearance compared to females.