What are the causes of hyperphosphatemia?
Hyperphosphatemia can be due to increased intake, transcellular distribution, and decreased kidney clearance.
Cathartics may contain sodium phosphate. When used as the principal bowel prep for colonoscopies and GI procedures, the recommended dose is 11.5 g of phosphorus in 90 mL of solution. Patients routinely become hyperphosphatemic, though usually only transiently. Increased age, abnormal bowel motility, and decreased kidney function are all risk factors for persistent and significant hyperphosphatemia. Similar results have been reported with sodium phosphate enemas.
In advanced CKD, increased dietary phosphorus is associated with hyperphosphatemia. Foods with high phosphorus need to be avoided in order to keep dietary phosphorus below 1200 mg for pre-dialysis CKD patients, and 800 mg for dialysis patients.
The anti-seizure medication, fosphenytoin is metabolized to phenytoin, formaldehyde, and phosphorus. Acute episodes of hyperphosphatemia have been reported in patients with kidney failure.
Cell breakdown in the setting of tumor lysis syndrome, rhabdomyolysis, or hemolysis releases intracellular phosphate. Breakdown of these cells also releases uric acid, myoglobin, and hemoglobin, respectively, resulting in acute kidney injury. This compromises the excretion of phosphate. With tumor lysis syndrome in particular, calcium phosphate, uric acid, and xanthine can precipitate in the tubules, resulting in inflammation and obstruction. Increased urine pH predisposes to the crystallization of calcium phosphate. Chemotherapy protocols that call for alkalinization of the urine to prevent uric acid nephropathy may unwittingly predispose to calcium phosphate precipitation.
Hyperphosphatemia is common in diabetic patients presenting with ketoacidosis. However, the phosphorus rapidly falls with treatment, and by 12 hours the phosphorus may be below normal. The increased phosphorus is due to transcellular shift and a lack of insulin. After treatment is initiated, phosphorus shifts back in the cells and reveals underlying total body phosphorus depletion.
PTH decreases kidney reabsorption of phosphorus, so decreases in PTH result in hyperphosphatemia. Hypoparathyroidism is most commonly seen as a complication of parathyroid, thyroid, or neck surgery. Both hypo- and hypermagnesemia can cause functional hypoparathyroidism. DiGeorge, or velocardiofacial syndrome due to a micro deletion of 22q11, is a congenital cause of hypoparathyroidism. Acromegaly is thought to cause hyperphosphatemia through the action of an insulin-like growth factor, which stimulates phosphorus reabsorption in the proximal tubule. Vitamin D toxicity increases both calcium and phosphorus absorption. The increased calcium suppresses PTH, which further compromises phosphorus excretion. Bisphosphonates induce a mild hyperphosphatemia by stimulating phosphorus reabsorption. Primary hyperphosphatemic tumoral calcinosis is a condition characterized by multiple calcified, painless masses. Patients have normal calcium levels but elevated phosphorus levels with normal kidney function. This is due to an inactivating mutation to FGF-23, Klotho, or GALNT3, resulting in decreased renal phosphorus excretion.
As mentioned earlier, decreased renal clearance is arguably the most important cause of hyperphosphatemia. In acute kidney injury, as kidney dysfunction resolves, so does the hyperphosphatemia. In early CKD, increases in FGF-23 and PTH are able to maintain the phosphorous balance, but as the GFR falls below 20 mL/min, the frequency of hyperphosphatemia begins to increase.
