Abstract: FR-PO422
Selumetinib-Induced Hyperphosphatemia in a Pediatric Patient: A Rare Adverse Event
Session Information
- Pediatric Nephrology - I
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Pediatric Nephrology
- 1800 Pediatric Nephrology
Authors
- Master sankar raj, Vimal, UICOMP, University of Illinois Chicago College of Medicine at Peoria, Peoria, Illinois, United States
- Narula, Megan, UICOMP, University of Illinois Chicago College of Medicine at Peoria, Peoria, Illinois, United States
Introduction
MEK, small molecule downstream inhibitors of Ras and Raf oncogenes are targets for oncological therapeutics in resistant malignancies. Selumetenib is one such MEK inhibitor used in Neurofibromatosis, type 1. We report the incidence of hyperphosphatemia, a rare adverse effect in a pediatric patient on treatment with the same.
Case Description
A 7-year-old girl was started on selumetinib for treatment of NF type I-related recurrent plexiform neurofibroma of the ankle. Prior to initiation, her serum phosphorus (P) was in the normal range for age at 5.4. Three weeks on therapy a rise in serum P was noted, reaching a peak of 6.7 approximately two months into treatment. Workup showed normal renal function with an estimated glomerular filtration rate (eGFR) >90 ml/min, parathyroid hormone normal at 37 pg/ml and alkaline phosphatse at 256 U/L. 25 hydroxy Vitamin D level was measured at 68 pg/ml and 1,25 dihydroxy Vitamin D at higher end of normal range at 80 pg/ml. Serum calcium level was 9.4 mg/dl with calcium phosphorus product ratio elevated at 63. Urine showed tubular reabsorption of phosphorus (TRP) of 90%, inappropriately elevated in the setting of hyperphosphatemia. Fibroblast growth factor 23 (FGF23) was measured and elevated at 55 pg/ml indicating resistance at the renal tubular level.
Discussion
The mitogen activated protein kinase (MAPK) cascade consisting of RAF/MEK/ERK molecular pathway regulates various aspects of cell survival, proliferation and differentiation via transducing signals from cell surface to nucleus. MEK is an attractive therapeutic target as it is the only known substrate in extracellular signal related kinase (ERK). MEK inhibition by altering cellular homeostasis has shown in toxicology studies of various adverse effects mimicking FGF23 or klotho knockout mice. The main phenotype is that of hyperphosphatemia, elevated 1,25 - dihydroxy vitamin D3 levels, and tissue mineralization indicative of renal resistance to FGF23. Pediatric literature on the adverse metabolic effect of selumetenib has not shown many issues with calcium or phosphorus homeostasis. The most common reported adverse effect is an increase in creatine phosphokinase. Here we report a case of isolated hyperphosphatemia noted after selumetenib initiation in a pediatric patient. This is likely due to FGF23 resistance as shown by elevated FGF23 levels and increased TRP with a normal GFR.