Hypophosphatemia: an evidence-based approach to its clinical consequences and management

Optimal cellular function is dependent on maintenance of a normal serum phosphorus concentration. Serum phosphorus concentration is affected by several determinants, the most important of which is regulation of phosphorus reabsorption by the kidney. The majority of this reabsorption (80%) occurs in the proximal tubule and is mediated by an isoform of the sodium-phosphate cotransporter (NaPi-II). Parathyroid hormone, via a variety of intracellular signaling cascades leading to NaPi-IIa internalization and downregulation, is the main regulator of renal phosphate reabsorption. Shift of phosphorus from extracellular to intracellular compartments, decreased gastrointestinal absorption, and increased urinary losses, are the primary mechanisms of hypophosphatemia, which affects approximately 2% of hospitalized patients. Hypophosphatemia has been implicated as a cause of rhabdomyolysis, respiratory failure, hemolysis and left ventricular dysfunction. With the exception of ventilated patients, there is little evidence that moderate hypophosphatemia has significant clinical consequences in humans, and aggressive intravenous phosphate replacement is unnecessary. By contrast, patients with severe hypophosphatemia should be treated. Intravenous repletion may be considered, especially for patients who have clinical sequelae of hypophosphatemia.