Abstract: SA-PO0212
Acalabrutinib-Associated Renal Phosphate Wasting: Case Series and Mechanistic Insight
Session Information
- Onconephrology: MGRS, HSCT, Electrolytes, RCC, and More
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Onconephrology
- 1700 Onconephrology
Authors
- Rohrer, Alex, Northeast Ohio Medical University, Rootstown, Ohio, United States
- Gaur, Mragank, University of Cincinnati, Cincinnati, Ohio, United States
- Gudsoorkar, Prakash Shashikant, University of Cincinnati, Cincinnati, Ohio, United States
Introduction
Isolated hypophosphatemia has been reported with the Bruton tyrosine kinase (BTK) inhibitor ibrutinib but not with the second-generation BTK inhibitor acalabrutinib. We describe three adults with chronic lymphocytic leukemia (CLL) who developed renal phosphate wasting on acalabrutinib and outline a proximal-tubule mechanism.
Case Description
When routine chemistry revealed low serum phosphate, we obtained concurrent serum calcium, magnesium, potassium, creatinine, parathyroid hormone, and vitamin D levels and spot urine chemistries. Fractional excretion of phosphate (FePO4) was calculated (Table1). Acalabrutinib (100 mg twice daily) was continued; oral sodium-phosphate 0.5–1 g three times daily was prescribed until serum phosphorus ≥ 3.2 mg/dL.
Oral replacement restored serum phosphorus to 3.4, 3.5, and 3.3 mg/dL after 4, 7, and 9 days, respectively, with durable normalization at 12 weeks and no decline in kidney function.
Discussion
Proposed mechanism: Although acalabrutinib is highly BTK-selective, it still inhibits the tyrosine kinase expressed in hepatocellular carcinoma (Tec) family kinase (9-fold less potently). Tec is expressed in renal proximal-tubule epithelium and anchors the sodium-phosphate cotransporter (NaPi-IIa) within a protein-kinase-C/extracellular-signal-regulated-kinase/Na/H-exchanger-regulatory-factor-1 (PKC/ERK/NHERF1) scaffold. Tec blockade mimics parathyroid hormone signaling, triggering NaPi-IIa internalization, which raises FePO4 and lowers serum P, while Ca, Mg, and K remain stable.
Conclusion: Acalabrutinib can result in reversible renal phosphate wasting due to presumed Tec-mediated NaPi-IIa destabilization. Regular phosphate monitoring and prompt oral supplementation enable uninterrupted BTK inhibition in CLL.