S152 Gastrointestinal Tract Injuries Associated With Sevelamer: A Systematic Review

Abstract

Introduction: Sevelamer is a phosphate binder that is used to treat hyperphosphatemia in patients with chronic kidney disease. Sevelamer is known to cause multiple gastrointestinal side effects including nausea, vomiting, constipation, and abdominal pain. However, sevelamer crystals were observed in rare cases in the gastrointestinal tract (GIT) with associated serious injuries including inflammation, ulceration, ischemia, and perforation. In this study, we conducted a systematic review to investigate the association of sevelamer with GIT injuries. Methods: We conducted a systematic search in MEDLINE, EMBASE, Scopus, and Cochrane Central Register of Controlled Trials to identify eligible reports of sevelamer-associated gastrointestinal tract injuries. The bibliographies of identified articles, Goggle scholars, and websites of relevant professional associations were also searched for relevant studies. Two independent reviewers identified eligible studies and data were extracted in Excel. Only studies that had sevelamer crystals seen in the histopathological exams were included. (Table) Results: We included 58 studies describing a total of 77 patients with a mean age of 58.8 years. Diabetes was present in 27% of cases and at least one risk factor to have slow GIT motility was identified in 63.3% of patients. Both sevelamer carbonate and sevelamer hydrochloride were reported to be associated with GIT injury. Gastrointestinal bleeding (44.2 %) and abdominal pain (37.7 %) were the most common presenting symptoms. The large intestines were the most common area of involvement (74 %), especially in the rectosigmoid area (36.4 %). Ulceration (52 %) and inflammation (48.1 %) were the most common histopathological findings. Stopping sevelamer was the most common pharmacological intervention. 20.8% of patients required surgical intervention, while 6.5% had an endoscopic intervention. Full recovery was reported in 45.5% while 6.5% of patients died. Conclusion: While sevelamer crystals can be found incidentally in the mucosa of the GIT, there is growing evidence that sevelamer use can be associated with GIT injury. Slow GIT motility can be an important risk factor to develop sevelamer-associated GIT injury. If a GIT injury was found during endoscopy and sevelamer crystals were identified on histopathological exam, discontinuing sevelamer and using an alternative phosphate binder should be considered. Further studies are needed to identify risk factors and the best approaches for primary and secondary prevention. Table 1. - Characteristics of included studies GIT: gastrointestinal tract, GIB: Gastrointestinal bleeding Demographics Age (years)Malesfemales 58.88 ± 10.934 (44.2 %)35 (44.5 %) Comorbidities DiabetesConstipationPrevious abdominal surgeryBlood thinnersPossible Slow GIT motility 27 (35.5 %)4 (5.2 %)15 (19.5 %)16 (20.8 %)49 (63.3%) Sevelamer treatment Sevelamer carbonateSevelamer hydrochlorideBothAverage doseMedian doseDuration 16 (20.8 %)12 (15.6 %)1 (1.3%)4,176.29 mg3,200.00 mg5 days – 7 years Symptoms GIBAbdominal painDiarrheaNausea/vomitingEsophageal dysphagia 34 (44.2 %)29 (37.7 %)12 (15.6 %)10 (13%)1 (1.3%) Location of GIT injury EsophagusStomachSmall IntestinesIleocecal valveLarge intestinesCecum and/or ascending colonTransverse ColonDescending colonRectosigmoidDiffuse colonic or unspecifiedAppendix 8 (10.4 %)8 (10.4 %)3 (3.9 %)3 (3.9 %)57 (74 %)8 (10.4 %)7 (9.1 %)1 (1.3%)28 (36.4 %)15 (19.5 %)2 (2.6 %) Histopathological abnormalities* UlcerationInflammationPerforationNecrosisIschemiaStrictureInflammatory polyp 40 (52 %)37 (48.1 %)14 (18.2 %)11 (14.3 %)6 (7.8 %)3 (3.9 %)3 (3.9 %) Pharmacological interventions Stopped SevelamerDecreased sevelamer doseContinued Sevelamer 35 (45.5 %)1 (1.3 %)1 (1.3 %) Procedural interventions Surgical interventionEndoscopic treatmentEndovascular intervention 16 (20.8)5 (6.5 %)1 (1.3 %) Outcomes RecoveredDeathNot reported 35 (45.5 %)5 (6.5 %)37 (48.1 %) *Includes both microscopic and macroscopic findings.