Kidney Week

Abstract: TH-OR071

Drug-Related Hypocalcemia in Patients with Malignancy: The Mediating Role of Serum Magnesium Levels

Session Information

• Onconephrology: Updates, Therapies, and Mechanisms
  November 06, 2025 | Location: Room 371A, Convention Center
  Abstract Time: 05:40 PM - 05:50 PM

Category: Onconephrology

• 1700 Onconephrology

Authors

• Suzuki, Kodai, Nagoya Shiritsu Daigaku Daigakuin Igaku Kenkyuka Igakubu, Nagoya, Aichi Prefecture, Japan

Kodai Suzuki, MD

• Murashima, Miho, Kinki Daigaku, Higashiosaka, Osaka Prefecture, Japan

Miho Murashima, MD, PhD

• Kasugai, Takahisa, Nagoya Shiritsu Daigaku Daigakuin Igaku Kenkyuka Igakubu, Nagoya, Aichi Prefecture, Japan

Takahisa Kasugai, MD

• Miyaguchi, Yuki, Nagoya Shiritsu Daigaku Daigakuin Igaku Kenkyuka Igakubu, Nagoya, Aichi Prefecture, Japan

Yuki Miyaguchi

• Tomonari, Tatsuya, Nagoya Shiritsu Daigaku Daigakuin Igaku Kenkyuka Igakubu, Nagoya, Aichi Prefecture, Japan

Tatsuya Tomonari

• Mizuno, Masashi, Nagoya Shiritsu Daigaku Daigakuin Igaku Kenkyuka Igakubu, Nagoya, Aichi Prefecture, Japan

Masashi Mizuno, MD, PhD

• Hamano, Takayuki, Nagoya Shiritsu Daigaku Daigakuin Igaku Kenkyuka Igakubu, Nagoya, Aichi Prefecture, Japan

Takayuki Hamano, MD, PhD

Background

Cetuximab and platinum-based agents are known to induce hypomagnesemia. Hypomagnesemia results in hypocalcemia through impaired parathyroid hormone secretion and skeletal resistance to its effects. We aimed to identify drugs associated with hypocalcemia in patients with malignancy and to investigate whether serum magnesium levels mediate these associations.

Methods

We conducted a retrospective cohort study of patients who received antineoplastic agents at our university hospital between 2018 and 2023. To identify drugs associated with hypocalcemia (corrected calcium <8.0 mg/dL), we employed multilevel mixed-effects logistic regression, incorporating malignancy type and individual patients as random effects. Mediation analyses were conducted to estimate the indirect effects of serum magnesium levels on these associations.

Results

A total of 5,474 patients were included. The median age was 67.8 [interquartile range: 56.6- 74.6] years, and the mean eGFR was 71.1 (20.7) mL/min/1.73 m². Among these patients, 410 (7.5%) developed hypocalcemia during the observation period. Zoledronate, high-dose denosumab (120 mg monthly), carboplatin, cisplatin, and cetuximab were significantly associated with hypocalcemia. These agents, except for high-dose denosumab, were also significantly associated with hypomagnesemia. Serum magnesium levels substantially mediated the association between cetuximab and hypocalcemia, whereas the mediating effects were minimal for the other agents.

Conclusion

Hypocalcemia during treatment with carboplatin or cetuximab was at least partially mediated by hypomagnesemia. In patients receiving these agents, appropriate magnesium supplementation may be beneficial in preventing hypocalcemia. In contrast, hypocalcemia associated with zolendronate, denosumab, or cisplatin was more likely attributable to the inhibition of bone resorption or impaired vitamin D activation secondary to tubular injury.

Factors associated with hypocalcemia and mediation by serum magnesium levels

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025rdn4szsc