Preloading magnesium attenuates cisplatin-associated nephrotoxicity: pilot randomized controlled trial (PRAGMATIC study)

Abstract

Background: Cisplatin is one of the most potent chemotherapeutic drugs used in head and neck cancer treatment; however, nephrotoxicity is the major side-effect limiting usage. Magnesium supplementation has been reported to reduce risk in non-controlled studies. We investigated whether preloading with magnesium prevents nephrotoxicity with a low-dose weekly cisplatin regimen.

Methods: We carried out a prospective pilot, single-blinded, randomized controlled trial to compare cisplatin-associated acute kidney injury (cis-AKI) and acute kidney disease (cis-AKD) between two groups: intravenous 0.9% NaCl 500 ml + KCL 20 mEq over 4 h pre-cisplatin 40 mg/m² weekly for 7-8 weeks (control group) compared with additional 16 mEq magnesium added to the saline infusion (Mg group) in 30 head and neck cancer patients. Cis-AKI was defined as an increased serum creatinine (SCr) ≥ 0.3 mg/dl within 7 days and cis-AKD is an increased SCr ≥ 0.3 mg/dl between last SCr and baseline pre-chemotherapy SCr.

Results: The overall cisplatin tumor response rate and survival were comparable between groups. The baseline characteristics were comparable between groups, although SCr was lower in the controls (0.70 ± 0.17 versus 0.87 ± 0.17 mg/dl, P = 0.01). The incidence of cis-AKI was similar (4.6% versus 1.3%); however, the incidence of cis-AKD was higher for the control group (46.7% versus 6.7%, hazard ratio = 0.082, 95% confidence interval 0.008-0.79, P = 0.03). The time to develop cis-AKD was significantly shorter in the control group (P = 0.007).

Conclusions: The magnesium-preloading regimen was safe and significantly showed a decreased incidence of cis-AKD. The encouraging results of our pilot study need to be confirmed in a large-scale randomized controlled trial.

Keywords: acute kidney disease; cisplatin nephrotoxicity; magnesium preloading.

Figure 1

Study Consolidated Standards of Reporting Trials (CONSORT) diagram. Number of patients who were recruited to the study, assigned to a study group and completed the protocol. AKI, acute kidney injury; CMT, chemotherapy; NSS, 0.9% NaCl.

Figure 2

Mean serum creatinine (A), estimated glomerular filtration rate (eGFR) (B), serum potassium (C) and serum magnesium (D) during study period amongst treatment groups. ∗P < 0.05 compared to baseline value in linear mixed effect model.

Figure 3

Mean serum creatinine changed compared to baseline creatinine and last creatinine (A) and mean estimated glomerular filtration rate (eGFR) change compared to baseline eGFR and last eGFR (B) amongst treatment groups. P value = paired t-test compared to baseline values.