{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T18:00:49Z","timestamp":1792864849407,"version":"4.5.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2020,10,13]],"date-time":"2020-10-13T00:00:00Z","timestamp":1602547200000},"content-version":"vor","delay-in-days":436,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Vifor Pharma Nordiska"},{"name":"Erasmus European programme"},{"DOI":"10.13039\/501100004348","name":"Stockholm County Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004348","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CIMED and Karolinska University Hospital"},{"name":"Swedish Renal Register"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Despite long-standing clinical use of sodium polystyrene sulphonate (SPS) for hyperkalaemia management in chronic kidney disease (CKD), its safety profile remains poorly investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We undertook an observational analysis of nephrology-referred adults with incident CKD Stage 4+ in Sweden during 2006\u201316 and with no previous SPS use. We studied patterns of use and adverse events associated to SPS initiation during follow-up. Patterns of SPS use were defined by chronicity of treatment and by prescribed dose. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) associated with SPS initiation (time-varying exposure) for the risk of severe (intestinal ischaemia, thrombosis or ulceration\/perforation) and minor (de novo dispensation of laxatives or anti-diarrheal drugs) gastrointestinal (GI) events.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 19\u00a0530 SPS-na\u00efve patients with CKD, 3690 initiated SPS during follow-up. A total of 59% took SPS chronically, with an average of three dispensations\/year. The majority (85%) were prescribed lower dosages than specified on the product label. During follow-up, 202 severe and 1149 minor GI events were recorded. SPS initiation was associated with a higher incidence of severe adverse events [adjusted HR 1.25 95% CI 1.05\u20131.49)], particularly in those receiving per label doses [1.54 (1.09\u20132.17)] and mainly attributed to ulcers and perforations. SPS initiation was also associated with higher incidence of minor GI events [adjusted HR 1.11 (95% CI 1.03\u20131.19)], regardless of dose, and mainly accounted for by de novo dispensation of laxatives.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Initiation of SPS in patients with advanced CKD is associated with a higher risk of severe GI complications as well as the initiation of GI-related medications, particularly when prescribed at per label doses.<\/jats:p><\/jats:sec>","DOI":"10.1093\/ndt\/gfz150","type":"journal-article","created":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T11:07:44Z","timestamp":1561979264000},"page":"1518-1526","source":"Crossref","is-referenced-by-count":77,"title":["Initiation of sodium polystyrene sulphonate and the risk of gastrointestinal adverse events in advanced chronic kidney disease: a nationwide study"],"prefix":"10.1093","volume":"35","author":[{"given":"Paola","family":"Laureati","sequence":"first","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"},{"name":"University of Milano-Bicocca, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Trevisan","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lovisa","family":"Schalin","sequence":"additional","affiliation":[{"name":"Vifor Pharma Nordiska AB, Glattbrugg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Illaria","family":"Mariani","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"},{"name":"University of Milano-Bicocca, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rino","family":"Bellocco","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"},{"name":"University of Milano-Bicocca, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manish M","family":"Sood","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Ottawa, Ottawa, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Barany","sequence":"additional","affiliation":[{"name":"Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arvid","family":"Sj\u00f6lander","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Evans","sequence":"additional","affiliation":[{"name":"Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan J","family":"Carrero","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,8,4]]},"reference":[{"key":"2021020415153545700_gfz150-B1","doi-asserted-by":"crossref","DOI":"10.1093\/ndt\/gfy249","article-title":"Plasma potassium ranges associated with mortality across stages of chronic kidney disease: the Stockholm CREAtinine Measurements (SCREAM) project","author":"Gasparini","year":"2019","journal-title":"Nephrol Dial Transplant"},{"key":"2021020415153545700_gfz150-B2","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1093\/eurheartj\/ehy100","article-title":"Serum potassium and adverse outcomes across the range of kidney function: a CKD Prognosis Consortium meta-analysis","volume":"39","author":"Kovesdy","year":"2018","journal-title":"Eur Heart J"},{"key":"2021020415153545700_gfz150-B3","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.ijcard.2017.07.035","article-title":"Incidence and determinants of hyperkalemia and hypokalemia in a large healthcare system","volume":"245","author":"Nilsson","year":"2017","journal-title":"Int J Cardiol"},{"key":"2021020415153545700_gfz150-B4","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1053\/j.ajkd.2017.09.003","article-title":"Potassium homeostasis in health and disease: a scientific workshop cosponsored by the National Kidney Foundation and the American Society of Hypertension","volume":"70","author":"Kovesdy","year":"2017","journal-title":"Am J Kidney Dis"},{"key":"2021020415153545700_gfz150-B5","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1681\/ASN.2010010079","article-title":"Ion-exchange resins for the treatment of hyperkalemia: are they safe and effective?","volume":"21","author":"Sterns","year":"2010","journal-title":"J Am Soc Nephrol"},{"key":"2021020415153545700_gfz150-B6","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1016\/j.amjmed.2015.05.040","article-title":"Management of hyperkalemia: an update for the internist","volume":"128","author":"Kovesdy","year":"2015","journal-title":"Am J Med"},{"key":"2021020415153545700_gfz150-B7","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.2215\/CJN.03700410","article-title":"Damned if you do, damned if you don\u2019t: potassium binding resins in hyperkalemia","volume":"5","author":"Watson","year":"2010","journal-title":"Clin J Am Soc Nephrol"},{"key":"2021020415153545700_gfz150-B8","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.2215\/CJN.03640415","article-title":"Randomized clinical trial of sodium polystyrene sulfonate for the treatment of mild hyperkalemia in CKD","volume":"10","author":"Lepage","year":"2015","journal-title":"Clin J Am Soc Nephrol"},{"key":"2021020415153545700_gfz150-B9","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1056\/NEJM196101192640303","article-title":"Management of hyperkalemia with a cation-exchange resin","volume":"264","author":"Scherr","year":"1961","journal-title":"N Engl J Med"},{"key":"2021020415153545700_gfz150-B10","doi-asserted-by":"crossref","first-page":"1924","DOI":"10.1681\/ASN.V9101924","article-title":"Effect of single dose resin-cathartic therapy on serum potassium concentration in patients with end-stage renal disease","volume":"9","author":"Gruy-Kapral","year":"1998","journal-title":"J Am Soc Nephrol"},{"key":"2021020415153545700_gfz150-B11","doi-asserted-by":"crossref","DOI":"10.1016\/j.amjmed.2012.08.016","article-title":"Gastrointestinal adverse events with sodium polystyrene sulfonate (Kayexalate) use: a systematic review","volume":"126","author":"Harel","year":"2013","journal-title":"Am J Med"},{"key":"2021020415153545700_gfz150-B12","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1097\/SMJ.0b013e31819e8978","article-title":"Intestinal necrosis due to sodium polystyrene sulfonate (Kayexalate) in sorbitol","volume":"102","author":"McGowan","year":"2009","journal-title":"South Med J"},{"key":"2021020415153545700_gfz150-B13"},{"key":"2021020415153545700_gfz150-B14","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/gastro\/gou011","article-title":"Kayexalate-induced colonic ulcer","volume":"2","author":"Albeldawi","year":"2014","journal-title":"Gastroenterol Rep (Oxf)"},{"key":"2021020415153545700_gfz150-B15","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1053\/j.ajkd.2012.04.023","article-title":"Association of prescription of oral sodium polystyrene sulfonate with sorbitol in an inpatient setting with colonic necrosis: a retrospective cohort study","volume":"60","author":"Watson","year":"2012","journal-title":"Am J Kidney Dis"},{"key":"2021020415153545700_gfz150-B16","first-page":"rjy138","article-title":"Sodium polystyrene sulfonate crystals in the gastric wall of a patient with upper gastrointestinal bleeding and gastric perforation: an incidental finding or a pathogenic factor?","volume":"6","author":"Hajjar","year":"2018","journal-title":"J Surg Case Rep"},{"key":"2021020415153545700_gfz150-B17","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1097\/00000478-200105000-00011","article-title":"Upper gastrointestinal tract injury in patients receiving kayexalate (sodium polystyrene sulfonate) in sorbitol: clinical, endoscopic, and histopathologic findings","volume":"25","author":"Abraham","year":"2001","journal-title":"Am J Surg Pathol"},{"key":"2021020415153545700_gfz150-B18","doi-asserted-by":"crossref","first-page":"e74","DOI":"10.14309\/crj.2018.74","article-title":"One oral dose of sodium polystyrene sulfonate associated with ischemic colitis and crystal deposition in colonic mucosa","volume":"5","author":"Edhi","year":"2018","journal-title":"ACG Case Rep J"},{"key":"2021020415153545700_gfz150-B19","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1080\/15563650.2018.1518529","article-title":"Gastroduodenal injury induced by orally administered sodium polystyrene sulfonate","volume":"57","author":"Nuzzo","year":"2019","journal-title":"Clin Toxicol (Phila)"},{"key":"2021020415153545700_gfz150-B20","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.jsps.2018.04.008","article-title":"Sodium polystyrene sulfonate induced intestinal necrosis; a case report","volume":"26","author":"Almulhim","year":"2018","journal-title":"Saudi Pharm J"},{"key":"2021020415153545700_gfz150-B21","doi-asserted-by":"crossref","DOI":"10.1001\/jamainternmed.2019.0631","article-title":"Risk of hospitalization for serious adverse gastrointestinal events associated with sodium polystyrene sulfonate use in patients of advanced age","author":"Noel","year":"2019","journal-title":"JAMA Intern Med"},{"key":"2021020415153545700_gfz150-B22"},{"key":"2021020415153545700_gfz150-B23","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1002\/pds.1294","article-title":"The new Swedish Prescribed Drug Register\u2014opportunities for pharmacoepidemiological research and experience from the first six months","volume":"16","author":"Wettermark","year":"2007","journal-title":"Pharmacoepidem Drug Safe"},{"key":"2021020415153545700_gfz150-B24","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1186\/1471-2458-11-450","article-title":"External review and validation of the Swedish national inpatient register","volume":"11","author":"Ludvigsson","year":"2011","journal-title":"BMC Public Health"},{"key":"2021020415153545700_gfz150-B25","first-page":"1","article-title":"KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease","volume":"3","year":"2013","journal-title":"Kidney Int Suppl"},{"key":"2021020415153545700_gfz150-B26","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1053\/j.ajkd.2014.01.416","article-title":"KDOQI US commentary on the 2012 KDIGO clinical practice guideline for the evaluation and management of CKD","volume":"63","author":"Inker","year":"2014","journal-title":"Am J Kidney Dis"},{"key":"2021020415153545700_gfz150-B27","doi-asserted-by":"crossref","first-page":"268","DOI":"10.7326\/M16-2607","article-title":"Sensitivity analysis in observational research: introducing the E-value","volume":"167","author":"VanderWeele","year":"2017","journal-title":"Ann Intern Med"},{"key":"2021020415153545700_gfz150-B28","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1159\/000360094","article-title":"Potassium-binding resins: associations with serum chemistries and interdialytic weight gain in hemodialysis patients","volume":"39","author":"Jadoul","year":"2014","journal-title":"Am J Nephrol"},{"key":"2021020415153545700_gfz150-B29","doi-asserted-by":"crossref","first-page":"2217","DOI":"10.1007\/s11255-017-1717-5","article-title":"Evaluation of the tolerability and efficacy of sodium polystyrene sulfonate for long-term management of hyperkalemia in patients with chronic kidney disease","volume":"49","author":"Georgianos","year":"2017","journal-title":"Int Urol Nephrol"},{"key":"2021020415153545700_gfz150-B30","first-page":"267","article-title":"Intestinal necrosis due to sodium polystyrene (Kayexalate) in sorbitol enemas: clinical and experimental support for the hypothesis","volume":"101","author":"Lillemoe","year":"1987","journal-title":"Surgery"},{"key":"2021020415153545700_gfz150-B31","doi-asserted-by":"crossref","first-page":"e0137636","DOI":"10.1371\/journal.pone.0137636","article-title":"Colon necrosis due to sodium polystyrene sulfonate with and without sorbitol: an experimental study in rats","volume":"10","author":"Ayoub","year":"2015","journal-title":"PLoS One"},{"key":"2021020415153545700_gfz150-B32","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1172\/JCI110131","article-title":"Mechanism of adrenal angiotensin II receptor changes after nephrectomy in rats","volume":"67","author":"Douglas","year":"1981","journal-title":"J Clin Invest"},{"key":"2021020415153545700_gfz150-B33","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1097\/00007611-200093050-00016","article-title":"Acute abdomen with colonic necrosis induced by Kayexalate-sorbitol","volume":"93","author":"Dardik","year":"2000","journal-title":"South Med J"},{"key":"2021020415153545700_gfz150-B34","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1097\/00000478-199701000-00007","article-title":"Necrosis of the gastrointestinal tract in uremic patients as a result of sodium polystyrene sulfonate (Kayexalate) in sorbitol: an underrecognized condition","volume":"21","author":"Rashid","year":"1997","journal-title":"Am J Surg Pathol"},{"key":"2021020415153545700_gfz150-B35","doi-asserted-by":"crossref","first-page":"261","DOI":"10.3390\/nu10030261","article-title":"Dietary approach to recurrent or chronic hyperkalaemia in patients with decreased kidney function","volume":"10","author":"Cupisti","year":"2018","journal-title":"Nutrients"}],"container-title":["Nephrology Dialysis Transplantation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/ndt\/article-pdf\/35\/9\/1518\/36195153\/gfz150.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/ndt\/article-pdf\/35\/9\/1518\/36195153\/gfz150.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T15:15:07Z","timestamp":1663859707000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ndt\/article\/35\/9\/1518\/5543535"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,4]]},"references-count":35,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2019,8,4]]},"published-print":{"date-parts":[[2020,9,1]]}},"URL":"https:\/\/doi.org\/10.1093\/ndt\/gfz150","relation":{},"ISSN":["0931-0509","1460-2385"],"issn-type":[{"value":"0931-0509","type":"print"},{"value":"1460-2385","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,9,1]]},"published":{"date-parts":[[2019,8,4]]}}}