Hypophosphatemia
Hypophosphatemia
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.
In recent years, numerous studies have evaluated the role of hyperphosphatemia in chronic kidney disease and dialysis patients. Less effort has gone into assessing the clinical significance of hypophosphatemia and scrutinizing its management. Identification of sodium-phosphate cotransporters and regulators of their expression and activity has shed light on the mechanisms of hypophosphatemia in diseases such as hyperparathyroidism, X-linked hypophosphatemia (XLH), autosomal dominant hypophosphatemic rickets and tumor-associated osteomalacia. Hypophosphatemia had previously been linked to rhabdomyolysis, hemolysis, and respiratory and cardiac failure. In spite of the prevalence of hypophosphatemia, these clinical consequences are not commonly encountered.
Severe hypophosphatemia might affect as few as 0.43% of hospitalized patients. Certain populations are likely to include a greater proportion of hypophosphatemic patientsfor example, alcoholics (0.9%), septic patients (2.4%), malnourished patients (10.4%), and patients with diabetic ketoacidosis (14.6%). In a retrospective study, severe hypophosphatemia was associated with a fourfold increase in mortality. Evidence for excess morbidity associated with moderate hypophosphatemia is much less definitive. This review critically evaluates the clinical consequences of moderate (1.0-2.5 mg/dl [0.32-0.80 mmol/l]) and severe (<1.0 mg/dl [<0.32 mmol/l]) hypophosphatemia, as well as safety issues regarding rapid correction of a low serum phosphorus concentration.
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.
In recent years, numerous studies have evaluated the role of hyperphosphatemia in chronic kidney disease and dialysis patients. Less effort has gone into assessing the clinical significance of hypophosphatemia and scrutinizing its management. Identification of sodium-phosphate cotransporters and regulators of their expression and activity has shed light on the mechanisms of hypophosphatemia in diseases such as hyperparathyroidism, X-linked hypophosphatemia (XLH), autosomal dominant hypophosphatemic rickets and tumor-associated osteomalacia. Hypophosphatemia had previously been linked to rhabdomyolysis, hemolysis, and respiratory and cardiac failure. In spite of the prevalence of hypophosphatemia, these clinical consequences are not commonly encountered.
Severe hypophosphatemia might affect as few as 0.43% of hospitalized patients. Certain populations are likely to include a greater proportion of hypophosphatemic patientsfor example, alcoholics (0.9%), septic patients (2.4%), malnourished patients (10.4%), and patients with diabetic ketoacidosis (14.6%). In a retrospective study, severe hypophosphatemia was associated with a fourfold increase in mortality. Evidence for excess morbidity associated with moderate hypophosphatemia is much less definitive. This review critically evaluates the clinical consequences of moderate (1.0-2.5 mg/dl [0.32-0.80 mmol/l]) and severe (<1.0 mg/dl [<0.32 mmol/l]) hypophosphatemia, as well as safety issues regarding rapid correction of a low serum phosphorus concentration.
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