Drug Criteria & Outcomes
Phosphate laxatives: The renal risk
By Wade Williams, PharmD Candidate, Auburn University Harrison School of Pharmacy
Oral sodium phosphate (OSP) products are commonly used for bowel cleansing, but many health care professionals are not aware of a serious adverse effect associated with these drugs. Acute phosphate nephropathy, a type of acute renal failure, is a missed cause of renal failure in patients with post oral sodium phosphate therapy. OSP products are commonly prescribed as a method of bowel cleansing prior to colonoscopy, radiographic procedures, and surgery. This method of bowel cleansing has been determined as the cause for acute renal failure in more than 20 documented cases where renal biopsies were taken, and many more cases without biopsies have shown an association with OSP products.
Oral products containing sodium phosphate include Fleet® Phospho-soda®, Fleet Accu-Prep®, Visicol®, and OsmoPrep™. The bowel cleansing doses of OSP solutions (two 45 mL doses prior to procedure) and Visicol (40 tablets) provide similar amounts of sodium phosphate: about 60 g per dose. OsmoPrep (tablet) is the latest OSP product and was approved in March 2006; the 32-tablet dose contains 48 g of sodium phosphate, and no cases of acute phosphate nephropathy have been associated with this product yet.
What is acute phosphate nephropathy?
Acute phosphate nephropathy is a type of nephrocalcinosis. Nephrocalcinosis is characterized as renal parenchymal calcium deposits that contribute to renal insufficiency and is usually linked to conditions associated with hypercalcemia. Acute phosphate nephropathy presents as acute renal failure with minimal proteinuria and bland urine sediment in patients recently receiving oral sodium phosphate. Calcium-phosphate crystal deposition in the distal tubules and collecting ducts along with acute or chronic renal tubular injury is seen in renal biopsy.
In the doses needed for bowel cleansing, oral sodium phosphate can cause decreased intravascular volume and hyperphosphatemia. Decreased intravascular volume stimulates reabsorption of water from the renal tubules, further increasing the phosphate concentration in renal tubular fluid. The abnormally high calcium phosphate concentration in the renal tubular fluid causes precipitation of calcium phosphate crystals in the kidney that leads to nephropathy.
Supporting data
A case series study describing 21 biopsy-proven cases of acute phosphate nephropathy in patients who were treated with OSP products for bowel cleansing was published in Nov. 2005; 16 of the 21 patients had a history of hypertension, and 14 were on an ACE inhibitor or angiotensin receptor blocker (ARB). The mean age was 64 years with 17 of the patients being female; only four patients had pre-existing renal insufficiency. One patient received Visicol tablets, and all other patients received Fleet Phospho-Soda or a generic equivalent. One patient received 120 mL of OSP solution over 12 hours, which significantly exceeds the recommended dose; however, all other patients received the standard dose. Average baseline serum creatinine was 1.0 mg/dL, and increased to an average of 3.9 mg/dL at a median of one month after colonoscopy. The time to discovery of acute renal failure post colonoscopy ranged from one day to five months.
Several other cases have been published showing renal failure following oral sodium phosphate treatment for bowel cleansing. A 76-year-old man received multiple doses of OSP solution and developed acute renal failure with a peak phosphorus level of 15.8 mg/dL. Hemodialysis quickly decreased phosphorus levels and renal function returned to normal one month later. Reports of OSP solution and tablets have been published as well. In addition, 20 cases have been reported to the FDA with half of those implicating the tablet dosage form.
The literature identifies patients that may be at a higher risk of acute phosphate nephropathy: patients with impaired renal function, reduced intravascular volume, or electrolyte abnormalities. Also, patients currently taking ACE inhibitors, ARBs, diuretics, or NSAIDs are believed to be at an increased risk. ACE inhibitors, ARBs, and NSAIDs can all decrease renal perfusion by dilation of renal arterioles. This becomes particularly problematic with volume depletion in which further reductions in perfusion exist, and diuretics may also cause volume depletion. Use of these medications should be monitored when considering a phosphate laxative.
FDA recommendations
- Avoid use of OSP in patients with kidney disease, impaired renal function of perfusion, dehydration, or uncorrected electrolyte abnormalities.
- Avoid exceeding recommended OSP doses and avoid concomitant use of laxatives containing sodium phosphate.
- Use OSP with caution in patients taking diuretics, ACE inhibitors, ARBs, and NSAIDs.
- Encourage patients to take the correct OSP dose and drink sufficient quantities of clear fluids during bowel cleansing.
- Obtain baseline and post-procedure labs (electrolytes, calcium, phosphate, BUN, and creatinine) in patients who may be at increased risk for acute phosphate nephropathy, including those with vomiting and/or signs of dehydration.
- Use hospitalization and intravenous hydration during bowel cleansing to support frail patients who may be unable to drink an appropriate volume of fluid or may be without assistance at home.
Options
Since there is no way to avoid bowel cleansing prior to colonoscopy, alternatives are needed for patients that are not good candidates for OSP products. Polyethylene glycol (Golytely®, Colyte®) is a safe and effective option, and it requires the patient to drink a large volume of fluid, which would reduce the risk of volume depletion. Many physicians and patients prefer the ease of OSP products; however, polyethylene glycol may offer a safer option for some patients.
Magnesium citrate is another option for bowel cleanings; however, this laxative is completely excreted renally and should also be used with extreme caution in patients with renal deficiency. Magnesium citrate may also cause a significant shift in fluid and electrolytes, and it is believed that an osmotically balanced product, such as polyethylene glycol, may be a safer alternative.
Conclusion
Acute phosphate nephropathy and chronic renal impairment are serious conditions that can occur with OSP bowel cleansing; however, these events are rare. OSP products for bowel cleansing involve a large phosphate load, fluid shifts, possible dehydration, and a rare adverse effect that can be devastating. Practitioners should be aware of the risk profile of OSP products and be able to determine which patients might be at an increased risk for nephropathy.
References
- Markowitz G, Stokes MB, Radhakrishnan J, et al. Acute phosphate nephropathy following oral sodium phosphate bowel purgative: An underrecognized cause of chronic renal failure. J Am Soc Nephrol 2005;16:3389-3396. Epub 2005 Sep 28.
- Orias M, Mahnensmith RL, Perazella MA. Extreme hyperphosphatemia and acute renal failure after a phosphorus-containing bowel regimen. Am J Nephrol 1999;19:60-63.
- Desmeules S, Bergeron MJ, Isenring P. Acute phosphate nephropathy and renal failure. N Engl J Med 2003;349:1006-1007.
- Fleet Laboratories. Available at: www.phosphosoda.com.
- Clark LE, Dipalma JA. Safety issues regarding colonic cleansing for diagnostic and surgical procedures. Drug Saf 2004;27:1235-1242.
- Food and Drug Administration. Food and Drug Administration Science Background Paper: Acute phosphate nephropathy and renal failure associated with the use of oral sodium phosphate bowel cleansing products. Available at: www.fda.gov. Accessed on: Nov. 6, 2007.
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