Sodium Polystyrene Sulfonate (SPS) is a commonly prescribed treatment for hyperkalemia. In 2009, the FDA recommended that it not be used with 70% sorbitol due to reports of colon perforation. In a recent article in the American Journal of Kidney Diseases, Watson and colleagues publish a single center retrospective cohort study aiming to identify the incidence and relative risk of colonic necrosis with SPS. In this interview, Dr. Christina Yuan (CY), corresponding author from Walter Reed National Military Medical Center, discusses their study with Dr. Vinay Nair (eAJKD), eAJKD Advisory Board member.
eAJKD: What were your reasons for performing this study?
CY: In the 1980s, there were case reports and case series that associated the use of SPS in sorbitol with colonic ischemia and colonic necrosis. This was especially true in post-surgical patients, patients with intestinal abnormalities, and in patients with advance kidney disease or kidney transplants. This was more likely to occur with rectal than with oral administration. Interestingly, animal data has suggested that it wasn’t so much the SPS, but was the 70% sorbitol that was given with the enema that seemed to cause the colonic injury.
However, subsequent case series observed colonic necrosis after SPS was administered orally with 33% sorbitol. In 2009, the FDA recommended that SPS sorbitol not be used immediately post-surgically, or in patients with compromised intestinal function. They also recommended that SPS should not be given as an enema with sorbitol, and that 70% sorbitol be avoided. In 2010, efficacy of resins was bought into question. We felt that the incidence of colonic necrosis was likely to be low, especially if it was used as recommended by the FDA. As there has never been a study done of the incidence of colon necrosis with SPS, we decided to explore this topic.
eAJKD: Can you summarize the results of your study?
CY: SPS was prescribed to 2194 hospitalized patients between September 2001 and October 2010. Eighty-two cases of colonic necrosis (CN) were identified hospital-wide, during the same time period. The data was linked with 123,391 hospitalized patients between the same dates. Three of these had colonic necrosis within 30 days of an SPS dose, indicating a number needed to harm of 1395. Using a pathologic diagnosis, we found that there was no outpatient prescription for SPS associated with a colonic necrosis within 30 days.
eAJKD: You used a timeframe of 30 days since the SPS treatment to assess for colonic necrosis. Is that a novel association?
CY: The 30-day window is used in the literature based on earlier case series. The incidence in the SPS group was about 0.14%, whereas it was 0.07% in the patients who did not receive SPS.
eAJKD:The study relies on pathology to confirm colon necrosis. Do you believe this could be a limitation in this study?
CY: We view this as a strength. Some studies determine the incidence of colonic necrosis based on clinical suspicion. Pathologic confirmation is necessary for the diagnosis in the gastroenterology literature. If someone develops colonic symptoms after SPS, people are much more likely to proceed to colonoscopy. Alternatively, patients who develop bowel symptoms while not taking SPS may be biased towards other diagnosis. There’s a Spanish study published in 2011 that showed the background incidence of colonic necrosis is about 0.13%, similar to our findings. They found that 76% of the cases were confirmed pathologically, and only 23% were probable.
eAJKD: As this is a retrospective study, do you believe the low rate of colonic necrosis may be explained by clinicians avoiding SPS in patients they consider high-risk?
CY: Yes, that is likely the case. There were very few enemas in our study. 99.3% of the patients who received SPS got it orally. There were only 36 prescriptions for enemas in over 5,100 cases.
eAJKD: Were kidney transplant patients included in your study?
CY: Yes, but none of the patients who developed colonic necrosis were kidney transplant recipients. The post-transplant association with colonic necrosis is probably due to the post-surgical risk.
eAJKD:Based on your data and review of the literature, how would you suggest clinicians deliver SPS in clinical practice?
CY: The recommendations of the FDA appear reasonable. SPS should be administered orally either in water or prepackaged in 33% sorbitol. It should not be used immediately post-surgery or in patients with other serious gastrointestinal conditions.
eAJKD:Do you believe further studies are warranted to evaluate the safety and efficacy of SPS in its various formulations?
CY: There is a population with chronic hyperkalemia, including those who require high dose renin-angiotensin blockade, patients with congestive failure, and those with diabetic nephropathy. A study by Pearl at al. was published in 2011 in the European Heart Journal looking at a new agent for this indication, but it used a placebo control. We think that SPS should be considered as an active control in these studies.