Sevelamer Carbonate Crystal-Induced Colitis

Abstract

Hyperphosphatemia is a common and well-described complication of end-stage renal disease. Despite strict dietary constraints and compliance, phosphate binders such as calcium acetate and/or sevelamer carbonate are also needed to treat secondary hyperparathyroidism. This case vignette describes an underrecognized adverse effect of a phosphate binder, sevelamer carbonate, inducing colitis in a 47-year-old male with insulin-dependent diabetes complicated by end-stage renal disease. He presented for recurrent abdominal pain with associated nausea and was found to have multiple circumferential lesions on computed tomography including distal ascending, transverse, and proximal descending colon. Colonoscopy demonstrated nearly obstructing lesions worrisome for colonic ischemia or inflammatory bowel disease. Pathological review of histology demonstrated ragged colonic mucosa with ulcerative debris and nonpolarizing crystalline material at the sites of ulceration, morphologically consistent with the phosphate binder, sevelamer carbonate. Sevelamer carbonate was discontinued, and the patient was transitioned to calcium carbonate with strict dietary restrictions. His symptoms improved with the cessation of sevelamer, and he was subsequently discharged home. He eventually underwent renal transplant without redevelopment of symptoms. Recognition of this underreported complication of sevelamer carbonate, phosphate binder, is of utmost importance in directing appropriate therapy with cessation of this medication in the setting of gastrointestinal complaints or more specifically enteritis and colitis. Clinicians providing care to end-stage renal patients taking either sevelamer and/or sodium polystyrene sulfonate should have increased awareness of the possible gastrointestinal side effects.

Advances in the treatment of secondary and tertiary hyperparathyroidism

“…Sevelamer is a primary drug of choice for SHPT ( 13 ). It rapidly reduces blood phosphorus concentration, inhibiting parathyroid cell proliferation and reducing PTH levels ( 14 ).…”

“…It rapidly reduces blood phosphorus concentration, inhibiting parathyroid cell proliferation and reducing PTH levels ( 14 ). However, its severe gastrointestinal side effects, such as vomiting and abdominal pain, greatly reduce patient compliance ( 13 ).…”

Sevelamer-Induced Gastrointestinal Disease in 12 Patients with End-Stage Renal Disease: A Case Series

“…Attributing the cause of severe GI events to sevelamer is challenging because there needs to be an established temporal relationship between the initiation of medication and onset of symptoms and healing after discontinuation. Of the several existing case reports, few have reported evidence of postdiscontinuation healing as observed by repeat endoscopy ( 5 , 6 ), rather most make inferences based on improvement of symptoms or do not address resolution of symptoms at all. Other case series demonstrate GI damage in the setting of sevelamer use and positive histology findings but do not comment on length of sevelamer use before diagnosis or resolution following discontinuation ( 7 , 8 ).…”

Association of Sevelamer Initiation with Gastrointestinal Bleeding Hospitalization in Individuals Requiring Hemodialysis

“…Sevelamer is an anion-exchange resin bound to either carbonate (Renvela ® ) or hydrochloride (Renagel ® ) and is prescribed to 40% of patients requiring dialysis in the USA [10]. Except for a small case series which included outpatients [11], the remaining published cases were in hospitalized patients with symptoms including hematochezia, constipation, and abdominal pain weeks to months after sevelamer initiation [7,8,[11][12][13][14][15][16][17][18][19][20][21][22][23][24]. Subsequent gastrointestinal biopsies from the esophagus, stomach, small intestine, and large intestine have shown a "fish-scale" appearance consistent with crushed sevelamer crystals [9,11,[13][14][15][16][17][18][25][26][27].…”

“…Except for a small case series which included outpatients [11], the remaining published cases were in hospitalized patients with symptoms including hematochezia, constipation, and abdominal pain weeks to months after sevelamer initiation [7,8,[11][12][13][14][15][16][17][18][19][20][21][22][23][24]. Subsequent gastrointestinal biopsies from the esophagus, stomach, small intestine, and large intestine have shown a "fish-scale" appearance consistent with crushed sevelamer crystals [9,11,[13][14][15][16][17][18][25][26][27]. Proposed mechanisms have included alterations in gastrointestinal motility, leading to crystalline deposition and ulceration [7,8] as well as increased risk with concurrent medication use such as sodium polystyrene sulfonate (Kayexalate ® ) [11,24].…”