The American Journal of Medicine
Volume 121, Issue 11 , Pages 931-932, November 2008

Are Oral Sodium Phosphate Products for Bowel Cleansing Safe for the General Population?

Division of Nephrology, University of Arizona, Tucson

Article Outline

 

Screening colonoscopy after the age of 50 years has become the standard method for prevention of colon or rectal malignancies. Although the procedure itself is not unbearable, dread associated with the preceding bowel preparation process often results in postponement of the procedure. For years researchers have sought the optimum bowel preparation; it seems that oral sodium phosphate might be that preparation.1 In brief, it is effective, economic, and most important, more palatable than swallowing 4 liters of polyethylene glycol in less than 3 hours.

Oral sodium phosphate is considered safe for the general population, without significant cardiovascular, renal, or gastrointestinal diseases. Only 1 to 5 serious experiences per million doses sold were reported to Fleet (Lynchburg, Va, the company sells Phospho-Soda), to the US Food and Drug Administration, or in the published literature.2 In 2004, Markowitz et al3 reported 5 cases of acute renal failure associated with oral sodium phosphate for bowel cleansing. The renal biopsies of these individuals revealed nephrocalcinosis, suggesting the pathogenetic role of oral sodium phosphate. Acute phosphate nephropathy has been used for this disease entity to distinguish it from other causes of nephrocalcinosis.4 These reports resulted in 2 Food and Drug Administration warnings. The labeling of oral sodium phosphate has been updated and now recommends cautious use by elderly patients and those with impaired renal function, heart disease, ascites, dehydration, and electrolyte disturbance. For the general population without these conditions, oral sodium phosphate remains the first choice for bowel preparation, with no data currently arguing against it.5 Is it possible that acute phosphate nephropathy will occur in this population?

Answering this question would require the participation of thousands of subjects in a prospective, blinded, randomized study. A shortcut is retrospective studies. Many such studies have been published recently with a similar design:6, 7, 8, 9

•Inclusion of hundreds or thousands of patients who had colonoscopy in the past few years;

•Exclusion of those without serum creatinine levels a few months before or after colonoscopy;

•Exclusion of those with “abnormal” baseline creatinine levels; and

•Analysis of changes in serum creatinine levels after colonoscopy results are analyzed and comparison across groups.

The results are all over the place: Oral sodium phosphate could be better, worse, or the same as polyethylene glycol.6, 7, 8, 9 The cardiovascular comorbidities may or may not be a risk factor for renal failure. The good news is that none of these studies detect patients who developed severe and irreversible renal failure as described by Markowitz et al.3 However, the bad news is that approximately 1% to 4% of these relatively healthy individuals did develop some degree of renal failure that might be irreversible. In one study, an increase of serum creatinine by 0.4 mg/dL was reported at the end of follow-up.8 Because the incidence of contrast nephropathy in the general population is in the range of 0.6% to 2%,10 oral sodium phosphate seems to be equally nephrotoxic as the intravenous contrast media. Obviously, physicians think twice before ordering a computed tomography scan with contrast but not before ordering a colonoscopy.

More recently, another worrisome report has been published.11 In this retrospective study, the oral sodium phosphate group was compared with a matched group without colonoscopy. Those undergoing colonoscopy with an oral sodium phosphate bowel preparation lost an average estimated glomerular filtration rate of 6 mL/min/1.73 m2 at 6 months after the procedure, whereas the control group had no loss. The loss seems to be permanent, because at 12 months the difference of 6 mL/min/1.73 m2 between the 2 groups remains. How does it happen? The standard dose of oral sodium phosphate is 45 mL taken 10 to 12 hours apart with a large amount of fluid. The total phosphorus load is 11.5 g, approximately 7- to 8-fold of normal dietary phosphorus. The high phosphorus intake from the first dose induces parathyroid hormone release.12 Both parathyroid hormone and high phosphorus intake down-regulate sodium phosphate cotransporters acutely by removing it from the apical membrane of the proximal tubule.13 As a result, the kidney will reabsorb less phosphate after the second dose. Patel et al14 reported important data on stool and urine phosphorus content after each dose of oral sodium phosphate. As shown in Figure 1, the gastrointestinal absorption of phosphorus is 50% and 37% for the first and second doses of oral sodium phosphate, respectively. The urine excretion of phosphate is 8% of the first dose but 21% of the second dose. Urine phosphorus concentration can be as high as 300 to 400 mg/dL.12 The precipitation of calcium phosphate is inevitable and confirmed by low urine calcium concentration (2-4 mg/dL). To protect the kidney, large amounts of fluid are needed to flush the precipitation out after colonoscopy, not just before the procedure.

  • View full-size image.
  • Figure 1. 

    Gastrointestinal absorption and renal excretion of phosphorus after standard dose of oral sodium phosphate based on the data reported by Patel et al.14 Each dose contains 5.75 g of phosphorus. The percentage of gastrointestinal absorption is calculated from the intake minus the mean stool phosphorus content, and the percentage of renal excretion is calculated from the mean urine phosphorus. GI, Gastrointestinal.

With this information, is oral sodium phosphate safe? We probably can handle the first dose, but the second one is likely to be too much even for normal kidneys. To reduce the risk of acute phosphate nephropathy, we might need to replace the second dose of oral sodium phosphate with other cleansing agents. We must continue to search for the optimum bowel preparation.

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References 

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  14. Patel V, Emmett M, Santa Ana CA, Fordtran JS. Pathogenesis of nephrocalcinosis after sodium phosphate catharsis to prepare for colonoscopy: intestinal phosphate absorption and its effect on urine mineral and electrolyte excretion. Hum Pathol. 2007;38:193–195

PII: S0002-9343(08)00758-4

doi:10.1016/j.amjmed.2008.07.018

The American Journal of Medicine
Volume 121, Issue 11 , Pages 931-932, November 2008

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