Introduction
Exposure to oral sodium phosphate can cause acute and chronic renal failure. Acute phosphate nephropathy occurs in individuals with compromised renal function if exposed to high phosphate doses. Phosphate nephropathy may result in abrupt or gradual loss of renal function over a period of time.
What Is Acute Phosphate Nephropathy?
Acute phosphate nephropathy is a pathological condition characterized by kidney injury following exposure to oral sodium phosphate (OSP) bowel purgatives. It causes acute renal failure and subsequent chronic renal failure. It is one of the reasons for drug-induced acute kidney injury. High doses of phosphate cause intratubular deposition of phosphate crystals resulting in injury to the kidneys.
Why Does Phosphate Toxicity Occur?
Phosphate is present in the human body's bones and exists as a phosphate anion. It is present in smaller amounts in the cells as organic phosphates and as inorganic phosphates in extracellular fluid. The average dietary intake of phosphorus is 1000 milligrams (mg) per day. About 60 to 80 percent of dietary phosphate gets absorbed in the small intestine. Excretion of phosphate occurs through glomerular filtration. However, major amounts of phosphate get reabsorbed in the proximal tubule, and small amounts of phosphate get reabsorbed in the collecting duct and distal tubule of the kidneys.
As most dietary phosphate gets reabsorbed, hyperphosphatemia can occur due to increased ingestion of phosphate over a short period of time, phosphate ingestion in the presence of impaired gastrointestinal motility, renal dysfunction causing decreased excretion of phosphate, or due to excessive release of intracellular phosphate in conditions like tumor lysis syndrome and rhabdomyolysis.
What Is Oral Sodium Phosphate?
Oral sodium phosphate solution (OSP) is a bowel purgative. It is used for bowel cleansing before the colonoscopy procedure. Oral sodium phosphate solution was preferred because of less discomfort, improved patient compliance, and high colonic cleansing ability compared to polyethylene glycol-based lavage solutions. It is also better tolerated than polyethylene glycol-based purgatives. It is also associated with transient hyperphosphatemia that usually resolves within 24 hours. Oral sodium phosphate solution is contraindicated in individuals with kidney failure, ascites, active inflammatory bowel disease, and congestive heart failure.
What Are the Effects of Oral Sodium Phosphate Solution on Kidneys?
The effects caused by oral sodium phosphate solution are referred to as acute nephrocalcinosis. The common form of nephrocalcinosis is associated with hypercalcemia related to hyperparathyroidism, sarcoidosis, malignancy, and milk-alkali syndrome. Oral sodium phosphate solution causes injury to the renal tubules.
A biopsy performed within three weeks of exposure to oral sodium phosphate solution showed acute tubular degenerative changes. It is accompanied by interstitial edema that involves all the tubular segments. A biopsy performed after three weeks of exposure to oral sodium phosphate solution showed the presence of chronic tubular atrophy and interstitial fibrosis.
As the interval from exposure to biopsy increases, the degenerative changes become less severe. This pattern of changes is described as acute and chronic tubulointerstitial nephropathy. Acute phosphate nephropathy is associated with mild-to-moderate interstitial inflammation. It is also associated with tubular changes and interstitial calcium phosphate deposits.
How Does Acute Phosphate Nephropathy Occur?
The elimination of phosphorus depends on the filtration rate and bioavailability of phosphorus in the blood. The majority of renal phosphorus gets absorbed in the proximal tubules. This increase in the phosphorus level or hyperphosphatemia can reduce the reabsorption of phosphorus in the proximal tubules of the kidneys following exposure to oral sodium phosphate. This results in hypovolemia, in which a large amount of phosphate is present at the distal nephron without being completely reabsorbed in the proximal tubules. Hypovolemia increases salt and water reabsorption. Hypovolemia combines with salt and water reabsorption and enhances the precipitation of calcium phosphate within the tubular lumen.
An increase in phosphorus levels induces calcium precipitation and reduces the reabsorption of calcium in the gastrointestinal tract. This reduction in ionized calcium concentration in blood induces parathyroid hormone as a compensatory mechanism. Parathyroid hormone accelerates the urinary calcium load and causes the formation of calcium phosphate crystals in the distal tubules and collecting ducts.
The calcium phosphate crystals bind with the tubular epithelial cells and cause the release of reactive oxygen species to impair the renal excretory pathway. Exposure to OSP solution causes phosphatemia and impairs the perfusion of the kidneys resulting in acute and chronic kidney disease. This can further cause the calcification of coronary arteries and may result in cardiovascular complications.
What Are the Signs and Symptoms of Acute Phosphate Nephropathy?
Phosphate nephropathy can present as developing a renal injury, renal failure, or remaining undiagnosed. The symptoms of phosphate nephropathy caused by OSP solution are similar to acute tubular necrosis. This includes the following:
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Diarrhea.
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Vomiting.
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Dehydration.
Hypotension and dehydration result in a dry mucous membrane, a decrease in skin turgor, and cool extremities. Apart from transient hyperphosphatemia, exposure to OSP solution can cause hypocalcemia (decreased calcium), hypernatremia (increased sodium concentration), and hypomagnesemia (decreased magnesium level).
How Is Acute Phosphate Nephropathy Diagnosed?
Various tests are performed to diagnose phosphate nephropathy.
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Serum phosphate, serum creatinine, and glomerular filtration rate are assessed. In phosphate nephropathy, the serum phosphorus and serum creatinine levels are elevated, and the glomerular filtration rate decreases.
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Urine microscopy with computed tomography scanning shows the presence of calcium phosphate crystals.
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Renal biopsy is an important criterion, and it is performed if the calcium and phosphorus levels are normal and the symptoms are nonspecific.
How Is Acute Phosphate Nephropathy Treated?
Early detection of phosphate nephropathy helps in timely intervention to decelerate calcium phosphate crystallization. Hemodialysis or peritoneal dialysis is performed to improve the excretion of calcium phosphate and the overproduction of reactive oxygen species at the site of damaged tubular epithelial cells. However, the complete recovery of renal function was reported to be rare.
Conclusion
Oral sodium phosphate solution induced acute phosphate nephropathy in susceptible individuals. It causes irreversible renal injury. It was banned in December 2008, but OSP tablets are available as prescription drugs. Acute phosphate nephropathy can be prevented by avoiding oral sodium phosphate solutions in high-risk individuals. OSP solution is not used currently, and other laxatives like polyethylene glycol (PEG), sodium picosulfate, and sodium laxatives are being used for bowel preparation.
