Kidney Week

Abstract: SA-PO1268

Putative Mechanisms of Hypophosphatemia Associated with Antineoplastic Agents

Session Information

• Onconephrology: Epidemiological Trends, Risk Stratification, and Clinical Outcomes
  October 24, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Onconephrology

• 1600 Onconephrology

Authors

• Manabe, Shohei, Kinki Daigaku Igakubu Daigakuin Igaku Kenkyuka, Sakai, Osaka Prefecture, Japan

Shohei Manabe, MD

• Murashima, Miho, Kinki Daigaku Igakubu Daigakuin Igaku Kenkyuka, Sakai, Osaka Prefecture, Japan

Miho Murashima, MD, PhD

• Okada, Nobutaka, Kinki Daigaku Igakubu Daigakuin Igaku Kenkyuka, Sakai, Osaka Prefecture, Japan

Nobutaka Okada, MD

• Kobayashi, Norihiro, Kinki Daigaku Igakubu Daigakuin Igaku Kenkyuka, Sakai, Osaka Prefecture, Japan

Norihiro Kobayashi, DrMed

• Nakatani, Yoshihisa, Kinki Daigaku Igakubu Daigakuin Igaku Kenkyuka, Sakai, Osaka Prefecture, Japan

Yoshihisa Nakatani, MD, MEd, PhD

• Arima, Shuji, Kinki Daigaku Igakubu Daigakuin Igaku Kenkyuka, Sakai, Osaka Prefecture, Japan

Shuji Arima, MD, PhD

Background

Hypophosphatemia is often overlooked despite its clinical importance. Patients with malignancy are at risk for hypophosphatemia due to malnutrition and drug-induced tubular injury. This study aimed to identify antineoplastic agents associated with hypophosphatemia and investigate putative underlying mechanisms.

Methods

We conducted a retrospective cohort study on patients with malignancy treated with antineoplastic agents from 2018 to 2023 in Kindai University Hospital. Hypophosphatemia was defined as serum phosphate concentration <2.0 mg/dL. Covariates were selected by the least absolute shrinkage and selection operator regression. Associations were examined using multilevel mixed-effects logistic regression with patient and malignancy type as random effects. Concomitant electrolyte abnormalities were analyzed using descriptive statistics. Whether the associations between antineoplastic agents and hypophosphatemia are mediated by weight loss was examined by mediation analyses.

Results

Among 10,500 patients, 3,131 with phosphate measurements were included. Mean age was 67.2 ±12.3 years, 62.9% were male, and the mean estimated glomerular filtration rate was 68.3±22.7 mL/min/1.73 m². The incidence of hypophosphatemia was 4.62 events per 100 patient-measurements. Cyclophosphamide and other alkylating agents were associated with hypophosphatemia, with odds ratios of 1.77 (95% CI, 1.16–2.49) and 2.21 (95% CI, 1.21–4.01), respectively. Three tyrosine kinase inhibitors (TKIs) were also associated with hypophosphatemia, with odds ratios ranging from 1.07 to 4.97. The proportions of concomitant hypomagnesemia and hypokalemia were higher among those with hypophosphatemia than those without hypophosphatemia. Mediation by weight loss was minimal (-2.6 to 6.9%).

Conclusion

Cyclophosphamide, other alkylating agents, and TKIs were associated with hypophosphatemia. Frequent concomitant hypomagnesemia and hypokalemia, with minimal mediation by weight loss, suggest tubular injury as a possible mechanism.

Funding

• Government Support – Non-U.S.