| Abstract|| |
Introduction: Kayexalate (Sodium Polystyrene Sulfonate/SPS) and K-bind (Calcium Polystyrene Sulfonate/CPS) are cation exchange resins, commonly used for treatment of hyperkalaemia. SPS/CPS induced injury of the gastrointestinal tract(GIT) is rare, can be potentially life threatening but is under-recognized. This study aims to increase awareness of pathologists and clinicians of this under-reported complication of a drug commonly used to treat hyperkalaemia. Materials: Study population comprised patients with SPS/CPS (Kayexalate or its analogues) crystals identified in gastrointestinal specimens from 2017-2019 at a tertiary care centre. Clinical details, relevant investigations, imaging and endoscopic findings, patient follow up details were obtained from the hospital electronic information system. Results: A total of 10 patients with SPS/ CPS crystals in the GIT were encountered over 2 years. Male to female ratio was 9:1, with mean age 66.5years (range 52-82 years). Eight cases were mucosal biopsies and 2 were resection specimens. Additional pathology (tumours, colonic perforation) was present in 80% of patients. The characteristic morphological appearance of the CPS/SPS crystals on H&E stains were supported by special stains -Periodic acid Schiff(PAS) and Acid fast Bacilli(AFB). In all cases, the treatment history with SPS/CPS for hyperkalaemia was obtained only after the histological examination. Most common etiology of hyperkalaemia encountered was chronic kidney disease(CKD)/ Acute on chronic kidney disease. Conclusion: It is important for pathologists to recognise the presence of these crystals especially in small biopsies as early feedback to clinicians can help in appropriate management and avoidance of more serious adverse outcome. To the best of our knowledge, this is the first series of 10 consecutive cases of SPS/CPS crystals encountered in gastrointestinal tract to be reported from India.
Keywords: GI injury, hyperkalemia, SPS/CPS crystals
|How to cite this article:|
Ail DA, Prakash A, Damle A, Karottue S, Paulose RR. SPS(Kayexalate)/CPS(K-Bind) crystals in the gastrointestinal tract-An experience from a tertiary center. Indian J Pathol Microbiol 2021;64:261-5
|How to cite this URL:|
Ail DA, Prakash A, Damle A, Karottue S, Paulose RR. SPS(Kayexalate)/CPS(K-Bind) crystals in the gastrointestinal tract-An experience from a tertiary center. Indian J Pathol Microbiol [serial online] 2021 [cited 2021 May 16];64:261-5. Available from: https://www.ijpmonline.org/text.asp?2021/64/2/261/313303
| Introduction|| |
Drug-induced gastrointestinal (GI) tract injuries mimic many other non-drug-related conditions. GI damage caused by crystal deposition including potassium binders such as sodium polystyrene sulfonate (SPS/Kayexalate)/calcium polystyrene sulfonate (CPS) is well-recognized., SPS/CPS have similar pharmacological actions and are used as mainstay treatment of acute and chronic hyperkalemia., The reported incidence of SPS/CPS drug-related GI injury is 1.8%. It can range from mild mucosal edema to fatal transmural necrosis and colonic perforation. SPS and CPS crystals in tissue are histomorphologically identical and mucosal changes induced by them are clinically and endoscopically easily confused with other GI diseases such as ischemia, infection, and inflammatory bowel disease (IBD). This study aimed to increase awareness of this underreported complication of a drug commonly used to treat hyperkalemia.
| Materials and Methods|| |
This is a study of 10 consecutive cases of SPS/CPS crystals in GI specimens including mucosal biopsies at our institute from 2017–2019. Patient details including demographics, presenting complaints, medical and surgical history, ancillary investigation (laboratory/imaging), and endoscopic findings were retrieved from the hospital information system.
SPS/CPS crystals in tissue were recognized as angulated rectangular/triangular, nonpolarizable, basophilic crystals, with a mosaic/fish scale pattern on hematoxylin and eosin (H and E) [Figure 1]b and [Figure 1]c, magenta color on periodic acid-Schiff (PAS) and black on acid-fast bacilli (AFB),, They were seen adherent to the surface epithelium/within sloughed, inflammatory exudates, and occasionally within the stroma.
|Figure 1: (a): Endoscopic image of 2 × 2 cm ulcer with edematous margin in the ileocecal valve, (b): Photomicroscopy of ileocecal mucosa showing multiple rhomboid/polygonal crystals in the lamina propria associated with ulceration H and E ×100, (c): Purple colored crystal with fish scaling on the surface H and E ×1000, (d): Kayexalate crystal appear magenta, PAS ×100|
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The presence of SPS/CPS crystals in the tissue was correlated with a history of SPS/CPS administration.
| Results|| |
Among the 10 patients, male to female ratio was 9:1, mean age 66.5 years (range 52–82 years). Presenting complaints included rectal bleeding with fall in hemoglobin level, abdominal pain, weakness, and diarrhoea. One patient presented with severe vomiting secondary to gastric outlet obstruction.
Colonoscopic findings included cecal ulceration, [Figure 1]a, colonic mucosal erosions, colonic polyps and malignancy. The patient with gastric outlet obstruction had an antral growth on oesophago-gastro endoscopy [Table 1].
The crystals were identified in mucosal biopsies in 8 patients and surgical resection specimens in 2 patients. The common site of injury was in the lower GI tract (ileum, ascending colon, descending colon, rectosigmoid, and descending colon) as seen in 9 patients. One patient had SPS/CPS crystals in a gastric biopsy.
Eight patients had other associated pathology - tumor/malignancies (colonic adenocarcinoma, extranodal marginal zone lymphoma of ascending colon, a neuroendocrine tumor of ileum, and multiple colonic polyps), and traumatic perforation of the colon [Table 1]
In all cases, the history of treatment with Kayexalate for hyperkalemia was obtained only after the histological identification of SPS/CPS crystals in the GI tissue. Laboratory investigations in all patients confirmed hyperkalemia at various times during their underlying illness (chronic kidney disease [CKD]/acute on CKD [n = 5], acute kidney injury [AKI], and electrolyte imbalance [hyperkalemia]). None of the patients had undergone renal transplantation.
On follow-up, two patients with colonic ulceration/erosion, in the absence of any other pathology were symptom-free after cessation of CPS/SPS. The others were treated for their associated pathology and discontinuation of the offending drug.
| Discussion|| |
SPS/CPS are ion exchange resins administered orally/rectally for treatment of acute/chronic hyperkalemia. After entering the GI lumen, sodium ions of SPS/calcium ions of CPS are exchanged for potassium ions in the colon, prompting excretion of potassium., Studies have shown that the resins can cause mucosal injury unrelated to its administration with/without sorbitol,, and currently they are emulsified in food or drink. In this series, CPS/SPS was administered orally with water.
The spectrum of GI damage attributed to SPS/CPS administration is varied. Lillemoe et al. first described the association between SPS and colonic necrosis in 1987. Others have described mild mucosal edema, erosion/ulceration, necrosis, perforation, pseudotumor, and rarely bezoars and intestinal obstruction.,,, Colon has been described as the most common site of injury followed by small intestine and stomach, as also noted in our series. Upper GI injury by SPS/CPS is rare with few reported cases in the esophagus, stomach including gastric perforation., Cases of hemorrhagic duodenitis and small bowel necrosis have also been reported.
Endoscopic picture of SPS induced injury generally is that of ischemia but it can be varying mimicking other conditions such as infections, inflammation, malignancy, or may appear nonspecific.
Radiologic evaluation is limited to the initial evaluation of symptoms. There are no characteristic radiologic features which can identify SPS/CPS as the etiology. The evaluation with barium or CT may show a mucosal thickening or nodularity, ulcers, perforation, or pseudotumors, all of which are nonspecific to SPS/CPS related injury.,, CT abdomen with enterography and intravenous contrast can however, identify skip lesions suggestive of Crohn's disease, ischemia and related ulceration, the ulcers of which may contain SPS/CPS crystals in those prescribed the same. The possibility of SPS/CPS piggybacking on these lesions should be a differential. Imaging can help in understanding the extent of the disease, especially in those areas not accessed by an endoscope.,
Histological evidence of SPS crystals at the mucosal injured site marks the “footprint” of its use, Morphological mimickers of these crystals are sevelamer and bile acid sequestrants (cholestyramine) crystals which are also ion exchange resins. Sevelamer is used for the treatment of hyperphosphatemia and has been associated with GI mucosal ulceration, ischemia, and necrosis Cholestyramine used to lower high levels of cholesterol and to sequester other substance such as thyroid hormone, bacterial toxins, and digoxin has not been associated with GI tract injury except occasionally seen entrapped in previously injured mucosa.,, The histological differentiating features of these crystals are detailed in [Table 2]., Atypical morphology of the sevelamer and cholestyramine crystals, potentially due to variable substrate binding and background pH can mimic SPS/CPS crystals., Rarely dystrophic calcification can also mimic SPS/CPS crystals but it appears bright purple and is devoid of the fish scale appearance on H and E stains. Raul et al. recommend AFB as a reliable ancillary stain as it stains black, sevelamer crystals as magenta, and cholestyramine yellow [Table 2]., Occasionally multiple crystals with different morphologies may be encountered and a good discussion with the clinician regarding treatment history can be reassuring.
|Table 2: Morphology of ion exchange resins encountered in GI Tract (Source: Gonzalez RS et al, Voltaggio L, et al)|
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The clinical scenario of CKD/end-stage renal disease with multiple episodes of hyperkalemia as reported in the literature was also noted in our series.,, Histological identification of these crystals should prompt the pathologist/clinicians to additionally look for potentially related conditions such as amyloidosis, CMV, HSV, mycophenolate induced changes, and so on.
Postoperative period due to the poor blood flow can also potentiate the injury induced by SPS/CPS.
Interestingly, in our series, 8 patients had associated neoplastic lesions (multiple colonic adenomatous polyps, colorectal adenocarcinoma, colonic extranodal marginal zone lymphoma, multiple well-differentiated neuroendocrine tumors of ileum, and gastric antral adenocarcinoma). In such cases, it is difficult to prove whether the crystals were directly or indirectly causative agents of mucosal ulceration. Pusztaszeri et al. described a case of jejunal diverticulitis with Kayexelate crystals and discussed the potential role of Kayexelate in the pathogenesis of diverticulitis., None of our patients died of Kayexalate induced injury.
Conservative treatment with the cessation of the offending drug is the standard therapy for superficial mucosal damages caused by the SPS/CPS. Recently, two new potassium binders, patiromer and sodium zirconium cyclosilicate have been reported to effectively treat hyperkalemia in patients with CKD not yet on dialysis. The long-term efficacy and safety of these novel potassium binders are yet to be determined among dialysis patients.
| Conclusion|| |
SPS/CPS induced injury of the GI tract is a rare and under-recognized iatrogenic complication frequently encountered in uremic patients. Treatment history should be sought in these scenarios. To our knowledge, this is the first series of 10 consecutive cases of SPS/CPS crystals histologically encountered in GI tissues to be reported from India.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Pusztaszeri MP, Genta RM, Cryer BL. Drug-induced injury in the gastrointestinal tract: Clinical and pathologic considerations. Nat Clin Pract Gastroenterol Hepatol 2007;4:442-53.
Parfitt JR, Driman DK. Pathological effects of drugs on the gastrointestinal tract: A review. Hum Pathol 2007;38:527-36.
Chou YH, Wang HY, Hsieh MS. Colonic necrosis in a young patient receiving oral kayexalate in sorbitol: Case report and literature review. Kaohsiung J Med Sci 2011;27:155-8.
Bui M, Chou SY, Faubert P, Loarte P, Cohen R. Resin-induced colonic pseudotumor: Rare complication from chronic use of potassium binders in a hemodialysis patient. Case Rep Nephrol 2016;2016:1-4.
Ribeiro H, Pereira E, Banhudo A. Colonic necrosis induced by calcium polystyrene sulfonate. GE-Port J Gastroenterol 2018;25:205-7.
Gayle S, Kistin M, Hanson J. An unusual cause of recurrent right lower quadrant pain. Dig Dis Sci 2014;59:1375-7.
Dunlap RH, Martinez R. Total colectomy for colon perforation after kayexalate administration: A case report and literature review of a rare complication. J Surg Case Rep 2016;2016:1-3.
Ayoub I, Oh MS, Gupta R, McFarlane M, Babinska A, Salifu MO. Colon necrosis due to sodium polystyrene sulfonate with and without sorbitol: An experimental study in rats. PloS One 2015;10:e0137636.
Okayama K, Hirata Y, Kumai D, Yamamoto Y, Kojima Y, Kanno T, et al
. The successful treatment of sodium polystyrene sulfonate-induced enteritis diagnosed by small bowel endoscopy. Intern Med 2018;57:1577-81.
Lillemoe KD, Romolo JL, Hamilton SR, Pennington LR, Burdick JF, Williams GM. Intestinal necrosis due to sodium polystyrene (Kayexalate) in sorbitol enemas: Clinical and experimental support for the hypothesis. Surgery 1987;101:267-72.
Almulhim AS, Hall E, Al Rehaili BM, Almulhim AS. Sodium polystyrene sulfonate induced intestinal necrosis; a case report. Saudi Pharm J 2018;26:771-4.
Desai M, Reiprich A, Khov N, Yang Z, Mathew A, Levenick J. Crystal-associated colitis with ulceration leading to hematochezia and abdominal pain. Case Reports Gastroenterol 2016;10:332-7.
Pusztaszeri M, Christodoulou M, Proietti S, Seelentag W. Kayexalate intake (in sorbitol) and jejunal diverticulitis, a causative role or an innocent bystander?. Case Reports Gastroenterol 2007;1:144-51.
Romano RC, Thirumala S, Cushman WH, Mounajjed T. Inflammatory pseudotumor containing Kayexalate crystals: A case report and review of the literature. Int J Surg Pathol 2014;22:464-9.
Oliveira AA, Pedro F, Craveiro N, Cruz AV, Almeida RS, Luís PP, et al
. Rectal ulcer due to Kayexalate deposition–an unusual case. Rev Assoc Méd Bras 2018;64:680-3.
Hajjar R, Sebajang H, Schwenter F, Mercier F. 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? J Surg Case Rep [Internet] 2018;2018. Available from: https://academic.oup.com/jscr/article/doi/10.1093/jscr/rjy138/5036897
. [Last cited on 2020 Feb 06].
Joo M, Bae WK, Kim NH, Han SR. Colonic mucosal necrosis following administration of calcium polystryrene sulfonate (Kalimate) in a uremic patient. J Korean Med Sci 2009;24:1207-11.
Marginean EC. The ever-changing landscape of drug-induced injury of the lower gastrointestinal tract. Arch Pathol Lab Med 2016;140:748-58.
Gonzalez RS, Lagana SM, Szeto O, Arnold CA. Challenges in diagnosing medication resins in surgical pathology specimens: A crystal-clear review guide. Arch Pathol Lab Med 2017;141;1276-82.
Voltaggio L, Lam-Himlin D, Limketkai BN, Singhi AD, Arnold CA. Message in a bottle: Decoding medication injury patterns in the gastrointestinal tract. J Clin Pathol 2014;67:903-12.
Abraham SC, Bhagavan BS, Lee LA, Rashid A, Wu TT. Upper gastrointestinal tract injury in patients receiving kayexalate (sodium polystyrene sulfonate) in sorbitol: Clinical, endoscopic, and histopathologic findings. Am J Surg Pathol 2001;25;637-44.
Gürtler N, Hirt-Minkowski P, Brunner SS, König K, Glatz K, Reichenstein D, et al
. Sodium polystyrene sulfonate and cytomegalovirus-associated hemorrhagic duodenitis: More than meets the eye. Am J Case Rep 2018;19:912.
Roopa R Paulose
Professor, Department of Pathology, Amrita Institute of Medical Sciences, Kochi - 682 041, Kerala
Source of Support: None, Conflict of Interest: None
[Table 1], [Table 2]