The Case | A kidney transplant patient with ileocecal inflammation
Authors: Mohamad Zaidan, Alexandre Loupy, Alexandre Rouquette, Pierre Philippe Massault, Frank Martinez, Christophe Legendre, Marie-France Mamzer-Bruneel
Journal: Kidney International (2013)

A 66-year-old woman was admitted for a 3-month history of severe weight loss, fever, night sweats, and abdominal pain at the right lower quadrant. Seven months earlier, she received a deceased donor kidney transplant for end-stage renal disease secondary to reflux nephropathy. She had been dialyzed for 33 years before transplantation and had a history of sporadic pheochromocytoma, hypertension, and new-onset diabetes after transplantation. Her medications included prednisone, mycophenolate mofetil, tacrolimus, cotrimoxazole, esomeprazole, atenolol, and metformin. On admission, her body temperature was 38.5°C, but physical examination was unremarkable. Laboratory investigations showed the following results: C-reactive protein, 58mg/l (N<6mg/l); white blood count, 11,000cells/mm3; and normal serum electrolytes and liver-function tests. Serum creatinine level was at its baseline value since transplantation (145μmol/l). T-Spot TB test and blood, urine, and sputum specimens’ cultures were negative. Serological tests for human immunodeficiency virus and hepatitis B and C virus were negative. The abdominal computed tomography scan showed an infiltration of pericecal fat, and focal thickening and inflammation of the ileocecal region, with high uptake of 18FDG on 18FDG-PET/CT scan (Figure 1). On exploratory laparotomy, the ileocecal region was thickened and inflamed with enlarged lymph nodes. A right hemicolectomy and lymph node resection were undertaken. Gross examination showed a large ileal ulcer of 6 × 4.5cm and a calcified foreign body of 2 × 0.3cm. Lightly basophilic and purple polygonal crystals were observed on hematoxylin–eosin–saffron stain (Figure 2).Figure 2Light microscopy examination with a close-up view showing lightly basophilic crystals in the lumen of the ileocecal ulcer (hematoxylin–eosin–saffron stain, original magnification × 100).View Large Image Figure ViewerDownload (PPT) What is your diagnosis? The ulcer contained typical sodium polystyrene sulfonate (SPS, Kayexalate) crystals with a characteristic striped and mosaic pattern on close-up view (Figure 2). SPS crystals were seen in the lumen and in the wall of the inflamed ulcer. The foreign body was also composed of an aggregation of SPS calcified crystals. Inflammatory cells and vascular thrombosis were identified in the surrounding tissues, but no evidence for calcific uremic arteriolopathy and tumoral and infectious lesions was observed. On re-interrogation, the patient reported intermittent intake of sorbitol-free SPS since transplantation. No further treatment was administered. The fever and inflammatory syndrome rapidly resolved, and the patient regained weight. In immunocompromised patients, such as kidney transplant recipients, persistent fever, night sweats, and weight loss, also called the ‘B symptoms’, call for awareness. This diagnostic conundrum may point to post-transplant lymphoproliferative disorders, malignancies, and severe infections, particularly tuberculosis and other opportunistic infections. Other inflammatory and dysimmune diseases, vascular thrombosis, and drug reactions are less frequent but should also be considered. As a thorough examination and basic investigations do not always provide enough diagnostic clues in the immunocompromised patient, further investigations may be helpful to guide the diagnosis. SPS is a US Food and Drug Administration–approved potassium binder used for the treatment of hyperkalemia.1.US Food and Drug AdministrationKayexalate (sodium polystyrene sulfonate) powder Prescribing Information.January 2011http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/011287s023lbl.pdfGoogle Scholar SPS-related intestinal necrosis and other serious gastrointestinal events have been reported mainly in small case series.2.McGowan C.E. Saha S. Chu G. et al.Intestinal necrosis due to sodium polystyrene sulfonate (Kayexalate) in sorbitol.South Med J. 2009; 102: 493-497Crossref PubMed Scopus (100) Google Scholar, 3.Sterns R.H. Rojas M. Bernstein P. et al.Ion-exchange resins for the treatment of hyperkalemia: are they safe and effective?.J Am Soc Nephrol. 2010; 21: 733-735Crossref PubMed Scopus (235) Google Scholar, 4.Watson M. Abbott K.C. Yuan C.M. Damned if you do, damned if you don’t: potassium binding resins in hyperkalemia.Clin J Am Soc Nephrol. 2010; 5: 1723-1726Crossref PubMed Scopus (80) Google Scholar The incidence and relative risk are difficult to assess considering the need for large cohort studies.5.Watson 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 (66) Google Scholar SPS-associated complications predominate on the ileum and colon, but may affect the upper gastrointestinal tract and include bleeding, ischemic colitis, focal to deep ulceration, necrosis and perforation, and fecal impaction with rectal stenosis.2.McGowan C.E. Saha S. Chu G. et al.Intestinal necrosis due to sodium polystyrene sulfonate (Kayexalate) in sorbitol.South Med J. 2009; 102: 493-497Crossref PubMed Scopus (100) Google Scholar, 3.Sterns R.H. Rojas M. Bernstein P. et al.Ion-exchange resins for the treatment of hyperkalemia: are they safe and effective?.J Am Soc Nephrol. 2010; 21: 733-735Crossref PubMed Scopus (235) Google Scholar, 4.Watson M. Abbott K.C. Yuan C.M. Damned if you do, damned if you don’t: potassium binding resins in hyperkalemia.Clin J Am Soc Nephrol. 2010; 5: 1723-1726Crossref PubMed Scopus (80) Google Scholar Reported risk factors include prematurity, history of intestinal disease, surgery or transplantation, hypovolemia, and renal failure.1.US Food and Drug AdministrationKayexalate (sodium polystyrene sulfonate) powder Prescribing Information.January 2011http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/011287s023lbl.pdfGoogle Scholar,2.McGowan C.E. Saha S. Chu G. et al.Intestinal necrosis due to sodium polystyrene sulfonate (Kayexalate) in sorbitol.South Med J. 2009; 102: 493-497Crossref PubMed Scopus (100) Google Scholar It is noteworthy that sorbitol, a cathartic often added to prevent obstipation, has been incriminated to trigger SPS-related serious gastrointestinal events.1.US Food and Drug AdministrationKayexalate (sodium polystyrene sulfonate) powder Prescribing Information.January 2011http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/011287s023lbl.pdfGoogle Scholar However, as in our patient, gastrointestinal complications with sorbitol-free SPS have also been documented.3.Sterns R.H. Rojas M. Bernstein P. et al.Ion-exchange resins for the treatment of hyperkalemia: are they safe and effective?.J Am Soc Nephrol. 2010; 21: 733-735Crossref PubMed Scopus (235) Google Scholar,4.Watson M. Abbott K.C. Yuan C.M. Damned if you do, damned if you don’t: potassium binding resins in hyperkalemia.Clin J Am Soc Nephrol. 2010; 5: 1723-1726Crossref PubMed Scopus (80) Google Scholar In the present case, considering the history of long-standing hemodialysis and hypertension, one cannot rule out that SPS may have exacerbated an underlying ischemic process owing to vascular calcifications or stenosis. Reports of SPS-related gastrointestinal damage are scarce but suggest that SPS may be harmful in at-risk patients. This case of particularly severe foreign-body reaction illustrates an unexpected cause of severe weight loss, fever, and abdominal pain in the renal transplant recipient, and a potential new aspect of SPS-associated serious gastrointestinal complications.