Pre-hydration may decrease the risk associated with the use of oral sodium phosphate solution.


SAN FRANCISCOThe use of phosphate-containing solutions to prepare the bowel for colonoscopy or surgery may cause significant damage to the kidneys, according to a researcher who spoke at a special clinical update here during Renal Week 2007.

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Glen Markowitz, MD, of Columbia University in New York, presented an update on the risks of acute and chronic renal failure related to the use of oral sodium phosphate solution (OSPS). This product is widely used to prepare bowels before procedures such as colonoscopy or surgery. In 2005, Dr. Markowitz and his colleagues reported on 21 cases of a rare but serious type of renal failure called acute phosphate nephropathy. Among the 21 patients, four ended up with permanent kidney failure requiring dialysis.


In 2006, the FDA issued an alert about this complication, including advice to avoid oral sodium phosphate solution in patients with kidney disease. Dr. Markowitz said that the FDA warning, together with careful selection of the most appropriate “bowel prep” for individual patients, may reduce the number of patients with this condition.


Five cases of acute phosphate nephropathy at five different centers were reported recently, and all involved women (age 56-85 years). None of the women returned to baseline renal function after the condition developed (Nephrol Dial Transplant. 2006;22:920-922). Dr. Markowitz said  that it may be possible to prevent additional cases of acute phosphate nephropathy in the future by better identifying risk factors.


For now, it appears that possible risk factors include female gender, small body habitus, and use of nonsteroidal anti-inflammatory drugs. Probable risk factors include inadequate hydration, advanced age, hypertension, treatment with angiotensin receptor blockade or diuretics, excess phosphate dosing, and a short interval between the two doses of OSPS, Dr. Markowitz said.


“This is a very important tissue,” said Dr. Markowitz, associate professor of clinical pathology and the associate director of renal pathology laboratory at Columbia. “The first principle of being a physician is [to] do no harm. This is a situation where we think we are doing no harm but because of new discoveries, we are learning that we are doing harm and we need to pay attention to these discoveries so that we don’t do more harm in the future. We need to look at the risk-benefit ratio. Since you are talking about perfectly healthy people going for screening colonoscopy to make sure they don’t have a precancerous polyp, you have to be very safe with that population.”


To determine the frequency of acute kidney injury (AKI) with OSPS use, researchers at Walter Reed Army Medical Center in Washington, D.C., performed an observational retrospective cohort study. Using electronic medical records, data were extracted from all patients age 50 and older who received a bowel purgative for colonoscopy from January 1, 2002 to May 31, 2006. The researchers excluded patients with end-stage renal disease and adjusted analyses for AKI risk factors. Patients who received a polyethylene glycol (PEG)-based purgative were included in the analysis as a comparison group.


The researchers, who reported their findings at the meeting, looked at a total of 16,826 patients who had a colonoscopy during this study period. Of these, 9,799 subjects (58%) had available serum creatinine values within 365 days before and after the procedure date. The investigators identified AKI in 114 patients (1.16%). After adjusting for significant covariates (age, diabetes mellitus, hypertension, and diuretic use) and other suspected risk factors for AKI (such as IV contrast exposure), use of OSPS was associated with a greater than twofold greater risk of AKI than an alternative agent, polyethylene glycol. In addition, older age was independently associated with AKI, the researchers reported.


“I do think we can reduce the risk,” Dr. Markowitz told Renal & Urology News. “If you drink a lot and don’t get dehydrated while you are doing a bowel prep, your risk is lower. The pharmaceutical companies have appropriately raised their requirements for hydration.” Another strategy is to reduce the phosphate content of the OSPS, he said, adding that companies are now making solutions with less phosphate in them.


Also at the clinical update, Daniel Coyne, MD, of Washington University School of Medicine in St. Louis, spoke about the risks of renal damage associated with bisphosphonates, a class of drugs which is used to treat osteoporosis and is unrelated to phosphate-based bowel purgatives. He noted that the risks are greater with nitrogen-containing formulations of these agents. The degree of risk may depend on the individual patient and the total dose over time. The kidney damage usually reverses after bisphosphonate treatment has stopped, he said.


Despite the risks, he told colleagues, bisphosphonates remain very important in treating the high rate of osteoporosis in patients with kidney disease. Recent studies have even suggested that bisphosphonates can slow buildup of calcium deposits in the blood vessels of patients on dialysis.