Abstract: FR-PO210
Hypercalcemia in a Patient with Cancer on an Immune Checkpoint Inhibitor, a Tyrosine Kinase Inhibitor, and Amiloride: Which Is the Culprit?
Session Information
- Onconephrology: Immunotherapy Nephrotoxicity and Assessment of GFR
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Onconephrology
- 1700 Onconephrology
Authors
- Saldanha Neves Horta Lima, Carolina, Mass General Brigham Salem Hospital, Salem, Massachusetts, United States
- Sise, Meghan E., Massachusetts General Hospital, Boston, Massachusetts, United States
- Gupta, Shruti, Brigham and Women's Hospital, Boston, Massachusetts, United States
Introduction
Hypercalcemia in oncologic patients can be malignancy-related, but can occur after immune checkpoint inhibitors (ICIs) and amiloride use.
Case Description
A 64-year-old patient with a history of stage IV renal cancer presents with fatigue, weakness and constipation. She was found to have AKI (creatine of 1.77 mg/dL from a prior of 0.9 mg/dL) and hypercalcemia of 13.7 mg/dL. She had been recently started on pembrolizumab, an ICI, and Lenvatinib (a tyrosine kinase inhibitor [TKI]). Within 24 hours of starting Lenvatinib, she had developed hypertension, requiring escalating doses of lisinopril, amlodipine, and metoprolol; amiloride was added for yet uncontrolled blood pressure. She denied use of excessive vitamin D supplements or antacids. Workup showed a 25 (OH)vitamin D of 71 ng/mL, a PTH of 8 pg/mL, a PTHrp of 0.7 pmol/L and a vitamin D 1,25 OH of 67 pg/mL. There was no disease progression or metastasis, pointing to a hypercalcemia not mediated by calcitriol and not cancer-related. Upon admission, amiloride was discontinued and patient received normal saline, calcitonin and pamidronate (Figure). There was normalization of calcium and creatinine.
Discussion
This case highlights, first, how TKI-related hypertension can present so quickly and severly. Thus, the need for further understanding of optimal anti-hypertensive therapies for these patients. And second, how the start of amiloride unmasked a hypercalcemia under ICI use. Amiloride acts by blocking sodium reabsorption through epithelial sodium channels. Amiloride-associated hypercalcemia is an entity mostly theoretical. It is thought to occur due to membrane hyperpolarization in the setting of sodium reabsorption, thereby promoting calcium entry. It is also possible that concurrent treatment with ICIs exacerbated the hypercalcemia, as ICIs have been reported to cause hypercalcemia by endocrinopathies, sarcoid-like granuloma, humoral hypercalcemia due to parathyroid-related hormone and hyperprogressive disease following ICI initiation.