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We appreciate the feedback from Yuan et al about our systematic review.1Harel Z. Harel S. Shah P.S. Wald R. Perl J. Bell C.M. Gastrointestinal adverse events with sodium polystyrene sulphonate (Kayexalate) use: a systematic review.Am J Med. 2013; 126: 264.e9-264.e24Abstract Full Text Full Text PDF PubMed Scopus (211) Google Scholar They note our inability to calculate the attributable risk of sodium polystyrene sulfonate–associated gastrointestinal injury because of the lack of a denominator and highlight the single-center study2Watson M.A. Baker T.P. Nguyen A. et al.Association of prescription of oral sodium polystyrene sulfonate with sorbitol in an inpatient setting with colonic necrosis: a retrospective cohort study.Am J Kidney Dis. 2012; 60: 409-416Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar of sodium polystyrene sulfonate–associated colonic necrosis. In that study, Watson et al2Watson M.A. Baker T.P. Nguyen A. et al.Association of prescription of oral sodium polystyrene sulfonate with sorbitol in an inpatient setting with colonic necrosis: a retrospective cohort study.Am J Kidney Dis. 2012; 60: 409-416Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar found a 9-year cumulative incidence of colonic necrosis of 0.14% in those prescribed sodium polystyrene sulfonate. Although this number may seem low, extrapolating this finding to the 5,000,000 doses of sodium polystyrene sulfonate given each year in the United States would yield 7000 cases of colonic necrosis per year.3Sterns R.H. Rojas M. Bernstein P. Chennupati S. Ion-exchange resins for the treatment of hyperkalemia: are they safe and effective?.J Am Soc Nephrol. 2010; 21: 733-735Crossref PubMed Scopus (227) Google Scholar Furthermore, as we have demonstrated in our review, despite colonic necrosis accounting for the majority of adverse gastrointestinal events associated with sodium polystyrene sulfonate, upper gastrointestinal injury is increasingly recognized as an important complication of sodium polystyrene sulfonate use; therefore, the study by Watson et al2Watson M.A. Baker T.P. Nguyen A. et al.Association of prescription of oral sodium polystyrene sulfonate with sorbitol in an inpatient setting with colonic necrosis: a retrospective cohort study.Am J Kidney Dis. 2012; 60: 409-416Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar likely underestimates the overall risk associated with this agent. Although we do agree with Yuan et al that all potential therapeutic options for hyperkalemia may be associated with side effects, the purpose of our review was to highlight the unique safety concerns associated with sodium polystyrene sulfonate therapy in light of the ongoing controversy surrounding its role in the management of hyperkalemia. This precluded us from commenting on the efficacy of sodium polystyrene sulfonate. However, a number of critical reviews3Sterns R.H. Rojas M. Bernstein P. Chennupati S. Ion-exchange resins for the treatment of hyperkalemia: are they safe and effective?.J Am Soc Nephrol. 2010; 21: 733-735Crossref PubMed Scopus (227) Google Scholar, 4Kamel K.S. Schreiber M. Asking the question again: are cation exchange resins effective for the treatment of hyperkalemia?.Nephrol Dial Transplant. 2012; 27: 4294-4297Crossref PubMed Scopus (33) Google Scholar, 5Kamel K.S. Wei C. Controversial issues in the treatment of hyperkalaemia.Nephrol Dial Transplant. 2003; 18: 2215-2218Crossref PubMed Scopus (87) Google Scholar of the efficacy of sodium polystyrene sulfonate in the management of hyperkalemia have disputed Watson et al's conclusion that sodium polystyrene sulfonate should remain “a viable option in the management of hyperkalemia when an excretory modality is required.”2Watson M.A. Baker T.P. Nguyen A. et al.Association of prescription of oral sodium polystyrene sulfonate with sorbitol in an inpatient setting with colonic necrosis: a retrospective cohort study.Am J Kidney Dis. 2012; 60: 409-416Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar Indeed, one review noted that the effect of sodium polystyrene sulfonate is “modest compared to that of inducing diarrhea.”4Kamel K.S. Schreiber M. Asking the question again: are cation exchange resins effective for the treatment of hyperkalemia?.Nephrol Dial Transplant. 2012; 27: 4294-4297Crossref PubMed Scopus (33) Google Scholar Although hyperkalemia-associated deaths are preventable with effective reduction in serum potassium, rigorous assessment of the optimal strategy, both in terms of safety and efficacy, is needed. Until then, physicians must be cognizant of the risk of adverse events when prescribing sodium polystyrene sulfonate therapy for the management of hyperkalemia in light of the ongoing debate regarding its efficacy. Incidence of Sodium Polystyrene Sulfonate-associated Colonic NecrosisThe American Journal of MedicineVol. 126Issue 9PreviewHarel et al1 systematically describe 58 patients with sodium polystyrene sulfonate (SPS)-associated gastrointestinal events. The majority of events (76%) involved the colon, and one third resulted in death. Their evaluation is rigorous and detailed. However, as they indicate in their discussion, the case series model is inherently limited by selection and publication bias, and the lack of a “denominator…to calculate attributable risk.” Full-Text PDF