Abstract
Phosphate is required for skeletal mineralization, cellular energy regulation, synthesis of cell membranes and nucleic acids, and a variety of cell signaling pathways. Extracellular serum phosphate concentration is determined by the balance of gastrointestinal phosphate absorption, skeletal turnover, distribution in intracellular compartments, and renal phosphate excretion. An integrated system of hormones, receptors, and phosphate transporters regulates phosphate homeostasis, and a variety of hereditary and acquired perturbations in these regulators can result in hyperphosphatemia. Although kidney failure is the most common cause of hyperphosphatemia encountered by nephrologists, hyperphosphatemia that presents in patients with early stages of chronic kidney disease or normal kidney function should prompt a detailed evaluation that can be diagnostically challenging. In this teaching case, we describe a case of hyperphosphatemia out of proportion to the degree of decrease in glomerular filtration rate. We present a practical parathyroid hormone-based diagnostic approach that illustrates the current understanding of phosphate regulation in clinically meaningful terms for the practicing nephrologist. Finally, we illustrate how measurement of fibroblast growth factor 23 could be integrated in the future when the test becomes more widely available.