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

INTRODUCTION: Isolated case reports and case series have linked the use of sevelamer to severe gastrointestinal (GI) inflammation and perforation among patients with end-stage renal disease. METHODS: In this study, we identified 12 cases of biopsy-proven sevelamer-induced gastrointestinal disease from a large urban community hospital over the course of 5 years. We described baseline characteristics, sites and types of injury, histological findings, timing and dosing of sevelamer initiation compared with symptom onset, and in a smaller subset, endoscopic resolution post drug cessation. We also reviewed preexisting conditions to identify trends in populations at risk. RESULTS: Several of the patients reviewed had preexisting conditions of decreased motility and/or impaired mucosal integrity. The presentation of disease was broad and included both upper-GI and lower-GI pathologies and in varying severity. DISCUSSION: There is a broad phenotypic range of sevelamer-induced gastrointestinal disease. As this becomes a more frequently recognized pathology, clinicians should be aware of how it may present and which populations may be more susceptible.

Patterns of gastrointestinal injury in patients with chronic kidney disease: Comparison of cases with and without sevelamer crystals.

AIMS: Sevelamer is a phosphate-binding resin implicated in gastrointestinal (GI) injury. This study aimed to investigate the role of sevelamer in GI injury among chronic kidney disease (CKD) patients. METHODS AND RESULTS: The study included 17 CKD patients (cases) with and 18 CKD patients (comparisons) without sevelamer crystals in specimens. All cases were on sevelamer. Six comparison patients were also taking sevelamer, but crystals were absent in tissue sections. The comparison group was thus subclassified into patients who were and were not taking sevelamer. The frequency of underlying disorders was similar between two groups, including hypertension (cases = 82%; comparisons = 78%) and diabetes mellitus (cases = 53%, comparisons = 50%). The most common presentation was GI bleeding (cases = 41%, comparisons = 33%). Predominant histological patterns were also similar, with ulcers (cases = 42%; comparisons = 39%) and acute ischaemia (cases = 35%; comparisons = 28%) being predominant in both cohorts. Of note, sevelamer was present with amyloidosis and cytomegalovirus in one study case each. Two study patients who continued sevelamer had follow-up biopsies; one showed persistent ulceration and the other appeared normal. Crystals were absent in both. CONCLUSIONS: GI injury in CKD patients in both groups had similar features regardless of presence of sevelamer, suggesting that it adheres to tissue rather than causes injury. The study highlights other histologically identifiable causes of intestinal injury, as well as injuries unassociated with sevelamer in patients undergoing therapy. Therefore, physicians should be cautious in attributing GI injuries to sevelamer to avoid overlooking other causes and unnecessary treatment discontinuation.

[Colonic Mass Secondary to Sevelamer-associated Rectal Ulcer].

The phosphorous balance is clinically important in increasing the long-term outcomes and preventing complications of end-stage renal disease. Sevelamer is a phosphate binder used widely to regulate hyperphosphatemia. On the other hand, gastrointestinal side effects increase with increasing sevelamer intake. A 29-year-old male with end-stage renal disease of IgA nephropathy on maintenance hemodialysis was admitted for diffuse alveolar bleeding and pneumonia. He presented with a low-grade fever and watery diarrhea tinged with blood. Initially, a Clostridioides difficile-associated diarrhea treatment was started with positive findings of Clostridioides difficile toxin and culture. Despite this, there was no improvement in the symptoms even with the appropriate antibiotic treatment. Computed tomography of the abdomen and pelvis revealed an occlusive mass in the rectum and secondary obstructive changes in the sigmoid colon. The initial suspicion was a malignancy or fungal infection. Sigmoidoscopy with a biopsy identified the mass as a lump of mucous material with the entire lumen covered with exudate. The subsequent histopathology examination revealed a colonic mucosal injury and characteristic "fish scale"-like sevelamer crystals in the exudate. The diagnosis of a sevelamer-induced rectal ulcer was made. We report this case of a sevelamer-associated rectal ulcer of the sigmoid.

Effectiveness of sucroferric oxyhydroxide in patients on on-line hemodiafiltration in real-world clinical practice: A retrospective study / Eficácia do oxihidróxido sucroférrico em pacientes em hemodiafiltração on-line na realidade da prática clínica: um estudo retrospectivo

Abstract Introduction: Hyperphosphatemia is a serious consequence of chronic kidney disease and has been associated with an increased risk for cardiovascular disease. Controlling serum phosphorus levels in patients on dialysis is a challenge for the clinicians and implies, in most cases, the use of phosphate binders (PB). Part of the reason for this challenge is poor adherence to treatment because of the high pill burden in this patient group. Objective: To assess the real-world effectiveness of sucroferric oxyhydroxide (SO) in controlling serum phosphorus levels and determine the associated pill burden. Methods: A multicenter, quantitative, retrospective, before-after study was conducted with patients receiving online hemodiafiltration. Patients who switched to SO as a part of routine care were included in the study. PB treatment, number of pills, serum phosphorus levels, and intravenous iron medication and dosage were collected monthly during the six months of treatment with either PB or SO. Results: A total of 42 patients were included in the study. After switching from a PB to SO, the prescribed pills/day was reduced 67% from 6 pills/day to 2 pills/day (p < 0.001) and the frequency of pill intake was lowered from 3 times/day to 2 times/day (p < 0.001). During the treatment with SO, the proportion of patients with serum phosphorus ≤ 5.5 mg/dL increased from 33.3% at baseline to 45% after six months of treatment. Conclusion: During the six-month follow-up with SO, serum phosphorus levels were controlled with one third of the pills/day compared to other PB.

Resumo Introdução: A hiperfosfatemia é uma grave consequência da doença renal crônica associada a risco aumentado de doença cardiovascular. O controle dos níveis séricos de fósforo dos pacientes em diálise é um desafio que requer, na maioria dos casos, o uso de quelantes de fosfato (QF). Parte da dificuldade se deve à baixa adesão ao tratamento oriunda do grande número de medicamentos receitados para esse grupo de pacientes. Objetivo: Avaliar a real eficácia do oxihidróxido sucroférrico (OHS) no controle dos níveis séricos de fósforo e determinar a carga de comprimidos associada. Métodos: Estudo multicêntrico, quantitativo, retrospectivo, antes e depois conduzido com pacientes em hemodiafiltração on-line. Pacientes remanejados para OHS como parte dos cuidados de rotina foram incluídos no estudo. Tratamento com QF, número de comprimidos, níveis séricos de fósforo, reposição férrica endovenosa e dosagens foram registrados mensalmente durante seis meses de tratamento com QF ou OHS. Resultados: Foram incluídos 42 pacientes no estudo. Após a mudança de QF para OHS, o número de comprimidos prescritos por dia caiu em 67%, de seis para duas unidades diárias (p < 0,001). A frequência de ingestão de comprimidos caiu de três para duas vezes ao dia (p < 0,001). Durante o tratamento com OHS, o percentual de pacientes com fósforo sérico ≤ 5,5 mg/dL aumentou de 33,3% no início para 45% após seis meses de tratamento. Conclusão: Durante os seis meses de seguimento com OHS, os níveis séricos de fósforo foram controlados com um terço dos comprimidos por dia em relação aos tratamentos com outros QF.

Pathology of Resin-Induced Gastrointestinal Damage: Report of 15 Cases and Review of Literature.

< strong > Objective: < /strong > Medication resins such as Kayexalate and Sevelamer used in the setting of chronic kidney disease for the correction of hyperkalemia and hyperphosphatemia are associated with gastrointestinal mucosal injury. In this study we describe the clinico-pathological features of Resin-induced gastrointestinal mucosal injury highlighting the histo-morphological appearances and differential diagnoses. The aim of this study is to increase the awareness of pathologists and clinicians alike to an under-reported etiology and pattern of intestinal mucosal injury related to medical resin therapy which may at times pose a clinical emergency. < strong > Material and Method: < /strong > The archives of the Department of Histopathology, Mubarak Al Kabir hospital were analyzed for cases of resin-induced gastrointestinal mucosal injury between 2013 and 2018. < strong > Results: < /strong > Of the 15 cases, Kayexalate crystals were identified in 7 cases, Sevelamer in 5 cases and both together were seen in 3 cases. Resin crystals were identified in the gastric antrum&duodenum (3 cases), colon (9 cases in the left colon, 2 cases in the right colon) and anal canal (1 case). The histological tissue reactions included mucosal necrosis (1 case), inflammatory polyps (2 cases), mucosal ulcerations with granulation tissue formation (10 cases), perforation (1 case) , and luminal crystals (1 case). < strong > Conclusion: < /strong > Accurate and timely recognition of the resin crystals in biopsy samples with clinical correlation is mandatory to avoid serious complications.

Sevelamer versus calcium-based phosphate binders for chronic kidney disease. / Sevelamer comparado con quelantes de fósforo en base a calcio para la insuficiencia renal crónica.

Chronic kidney disease-mineral and bone disorder is prevalent. There is controversy regarding whether calcium-based phosphate binders or sevelamer - a non-calcium phosphate binder – constitute a better therapeutic alternative. Searching in Epistemonikos database, which is maintained by screening multiple information sources, we identified 12 systematic reviews comprising 61 studies of which 41 correspond to randomized trials addressing the question of this article. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded sevelamer may decrease hypercalcemia, but with a higher incidence of gastrointestinal effects than calcium based phosphate binders. It is unclear if there are differences in mortality because the certainty of the evidence is very low.

Los trastornos minerales y óseos asociados a la enfermedad renal crónica son frecuentes. Para su tratamiento existen quelantes de fósforo en base a calcio y otros no cálcicos como el sevelamer, pero no está claro cuál constituye una mejor opción. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en múltiples fuentes de información, identificamos 12 revisiones sistemáticas que en conjunto incluyen 61 estudios primarios, de los cuales 41 corresponden a ensayos aleatorizados. Extrajimos los datos, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. Concluimos que el sevelamer, en comparación con los quelantes de fósforo en base a calcio, podría disminuir los eventos de hipercalcemia, pero con una mayor incidencia de efectos gastrointestinales. Por otra parte, no está claro si existen diferencias en cuanto a mortalidad porque la certeza de la evidencia es muy baja.

A case report of sevelamer-associated recto-sigmoid ulcers.

BACKGROUND: Optimal phosphorous control is an important aspect of the care of patients with end-stage renal disease, and phosphate binders are usually needed. CASE PRESENTATION: A 74-year-old woman with end-stage renal disease on maintenance hemodialysis presented to the emergency room with abdominal discomfort, rectal pain, and blood-tinged stools. Initial concern was for a rectal carcinoma, based on the symptoms and imaging in initial computerized tomography of the abdomen showing rectal wall thickening, and her clinical presentation. She had been treated with the phosphate binder sevelamer for two months. In this case report, we explore the unique features of sevelamer-associated recto-sigmoid ulcers which led to her symptoms. CONCLUSION: Sevelamer is widely used in chronic kidney disease and end-stage renal disease patients with hyperphosphatemia. It is a crosslinked polymeric amine that binds phosphates and bile acids; it is not systemically absorbed. To the authors' knowledge, this is the first reported case of recto-sigmoid ulcers associated with use of this phosphate binder. Nephrologists, pathologists, and gastroenterology sub-specialists should be aware of this recently-reported entity in patients on sevelamer with suggestive symptoms, as this medication is widely used in renal patients.