Postoperative Care of the Intestinal Recipient: Graft Monitoring, Nutrition, and Management of Medical Complications

Reference work entry
Part of the Organ and Tissue Transplantation book series (OTT)

Abstract

Significant improvements have been made in early outcomes following pediatric intestinal transplantation (ITx), yet long-term survival remains challenged by infection and rejection, both of which can present with diarrhea. While stool studies and endoscopy remain the gold standard for graft monitoring, less-invasive, timely, and accurate biomarkers are essential to help improve results. The use of calprotectin, citrulline, donor-specific antibodies, and other novel biomarkers is reviewed in this chapter. Nutrition following ITx is challenged by oral aversion, increased energy needs, malabsorption, and limited catch-up growth. Long-term growth and weight gain post-ITx can be predicted by hospitalizations, rejection, infection, and immunosuppression requirements. Deficiencies in micronutrients, including iron, zinc, and copper, as well as vitamins are commonplace post-ITx and require routine screening. Notable complications following ITx result from the high immunosuppression needs of these children and include tissue invasive CMV (7% prevalence), PTLD (15–20%), infectious enteritis (39–76%), and renal insufficiency (16%).

Keywords

Biomarkers Calprotectin Citrulline CMV Donor-specific antibodies EBV Endoscopy Infectious enteritis Micronutrients Nutrition PTLD Renal insufficiency 

References

  1. Abu-Elmagd KM et al (2009) Lymphoproliferative disorders and de novo malignancies in intestinal and multivisceral recipients: improved outcomes with new outlooks. Transplantation 88(7):926–934CrossRefPubMedGoogle Scholar
  2. Abu-Elmagd KM et al (2012) Preformed and de novo donor specific antibodies in visceral transplantation: long-term outcome with special reference to the liver. Am J Transplant 12(11):3047–3060CrossRefPubMedGoogle Scholar
  3. Akpinar E et al (2008) Fecal calprotectin level measurements in small bowel allograft monitoring: a pilot study. Transplantation 85(9):1281–1286CrossRefPubMedGoogle Scholar
  4. Alegre ML, Mannon RB, Mannon PJ (2014) The microbiota, the immune system and the allograft. Am J Transplant 14(6):1236–1248CrossRefPubMedPubMedCentralGoogle Scholar
  5. Alonso EM (2008) Growth and developmental considerations in pediatric liver transplantation. Liver Transpl 14(5):585–591CrossRefPubMedGoogle Scholar
  6. Altimari A et al (2008) Blood monitoring of granzyme B and perforin expression after intestinal transplantation: considerations on clinical relevance. Transplantation 85(12):1778–1883CrossRefPubMedGoogle Scholar
  7. Asaoka T et al (2011) Characteristic immune, apoptosis and inflammatory gene profiles associated with intestinal acute cellular rejection in formalin-fixed paraffin-embedded mucosal biopsies. Transpl Int 24(7): 697–707CrossRefPubMedGoogle Scholar
  8. Asaoka T et al (2012) MicroRNA signature of intestinal acute cellular rejection in formalin-fixed paraffin-embedded mucosal biopsies. Am J Transplant 12(2): 458–468CrossRefPubMedGoogle Scholar
  9. Ashokkumar C et al (2009) Allospecific CD154+ T cells identify rejection-prone recipients after pediatric small-bowel transplantation. Surgery 146(2):166–173CrossRefPubMedGoogle Scholar
  10. Ashokkumar C et al (2010) Allospecific CD154+ B cells associate with intestine allograft rejection in children. Transplantation 90(11):1226–1231CrossRefPubMedGoogle Scholar
  11. Brown KH (1998) Effect of infections on plasma zinc concentration and implications for zinc status assessment in low-income countries. Am J Clin Nutr 68(2 Suppl):S425–S429CrossRefGoogle Scholar
  12. Chen CC et al (2007) Clinicopathological analysis of hematological disorders in tube-fed patients with copper deficiency. Intern Med 46(12):839–844CrossRefPubMedGoogle Scholar
  13. Ching N et al (2010) Adenovirus infection and anti-viral treatment in pediatric solid organ transplant patients. Oral Presentation Pediatric Academic Societies Annual Meeting. Vancouver, Canada, 1–4, 2010.Google Scholar
  14. Colomb V, Goulet O (2009) Nutrition support after intestinal transplantation: how important is enteral feeding? Curr Opin Clin Nutr Metab Care 12(2):186–189CrossRefPubMedGoogle Scholar
  15. Curis E, Crenn P, Cynober L (2007) Citrulline and the gut. Curr Opin Clin Nutr Metab Care 10(5):620–626CrossRefPubMedGoogle Scholar
  16. David AI et al (2007) Blood citrulline level is an exclusionary marker for significant acute rejection after intestinal transplantation. Transplantation 84(9): 1077–1081CrossRefPubMedGoogle Scholar
  17. Dharnidharka VR (2002) Post-transplant lymphoproliferative disorder in the United States: young Caucasian males are at highest risk. Am J Transplant 2(10): 993–998CrossRefPubMedGoogle Scholar
  18. Encinas JL et al (2006) Nutritional status after intestinal transplantation in children. Eur J Pediatr Surg 16(6): 403–406CrossRefPubMedGoogle Scholar
  19. Farmer DG et al (2015) Predictors of outcome after intestinal transplantation: an analysis of over 125 cases at a single center. Oral Presentation International Small Bowel Transplant Symposium, Buenos Aires, Argentina. 2015Google Scholar
  20. Fishbein TM (2009) Intestinal transplantation. N Engl J Med 361(10):998–1008CrossRefPubMedGoogle Scholar
  21. Florescu DF et al (2010) Adenovirus infections in pediatric small bowel transplant recipients. Transplantation 90(2):198–204CrossRefPubMedGoogle Scholar
  22. Florescu DF et al (2011) Is there a role for oral human immunoglobulin in the treatment for norovirus enteritis in immunocompromised patients? Pediatr Transplant 15(7):718–721CrossRefPubMedGoogle Scholar
  23. Florescu DF et al (2012) Incidence, risk factors, and outcomes associated with cytomegalovirus disease in small bowel transplant recipients. Pediatr Transplant 16(3):294–301CrossRefPubMedGoogle Scholar
  24. Girlanda R et al (2012) Metabolomics of human intestinal transplant rejection. Am J Transplant 12(4 Suppl):S18S–SS26CrossRefGoogle Scholar
  25. Grant D et al (2015) Intestinal transplant registry report: global activity and trends. Am J Transplant 15(1): 210–219CrossRefPubMedGoogle Scholar
  26. Hayton BA, Broome HE, Lilenbaum RC (1995) Copper deficiency-induced anemia and neutropenia secondary to intestinal malabsorption. Am J Hematol 48(1):45–47CrossRefPubMedGoogle Scholar
  27. Hibi T et al (2012) Citrulline level is a potent indicator of acute rejection in the long term following pediatric intestinal/multivisceral transplantation. Am J Transplant 12(4 Suppl):S27–S32CrossRefPubMedGoogle Scholar
  28. Iyer K et al (2002) Nutritional outcome and growth of children after intestinal transplantation. J Pediatr Surg 37(3):464–466CrossRefPubMedGoogle Scholar
  29. Konikoff MR, Denson LA (2006) Role of fecal calprotectin as a biomarker of intestinal inflammation in inflammatory bowel disease. Inflamm Bowel Dis 12(6):524–534CrossRefPubMedGoogle Scholar
  30. Kowalski RJ et al (2006) Assessing relative risks of infection and rejection: a meta-analysis using an immune function assay. Transplantation 82(5):663–668CrossRefPubMedGoogle Scholar
  31. Kumar AR et al (2011) Proteomic analysis reveals innate immune activity in intestinal transplant dysfunction. Transplantation 92(1):112–119CrossRefPubMedPubMedCentralGoogle Scholar
  32. Lacaille F et al (2008) Long-term outcome, growth and digestive function in children 2 to 18 years after intestinal transplantation. Gut 57(4):455–461CrossRefPubMedGoogle Scholar
  33. Lukacik M, Thomas RL, Aranda JV (2008) A meta-analysis of the effects of oral zinc in the treatment of acute and persistent diarrhea. Pediatrics 121(2): 326–336CrossRefPubMedGoogle Scholar
  34. Mathew JM et al (2015) Role of innate and acquired immune mechanisms in clinical intestinal transplant rejection. Transplantation 99(6):1273–1281CrossRefPubMedGoogle Scholar
  35. McColl KE (2009) Effect of proton pump inhibitors on vitamins and iron. Am J Gastroenterol 104(2 Suppl):S5–S9CrossRefPubMedGoogle Scholar
  36. McDiarmid SV et al (1999) Factors affecting growth after pediatric liver transplantation. Transplantation 67(3): 404–411CrossRefPubMedGoogle Scholar
  37. Mercer DF et al (2011) Stool calprotectin monitoring after small intestine transplantation. Transplantation 91(10): 1166–1171CrossRefPubMedGoogle Scholar
  38. Mohan S et al (2012) Donor-specific antibodies adversely affect kidney allograft outcomes. J Am Soc Nephrol 23(12):2061–2071CrossRefPubMedPubMedCentralGoogle Scholar
  39. Nassif S et al (2013) Clinicopathologic features of post-transplant lymphoproliferative disorders arising after pediatric small bowel transplant. Pediatr Transplant 17(8):765–773CrossRefPubMedGoogle Scholar
  40. Ningappa M et al (2012) Mucosal plasma cell barrier disruption during intestine transplant rejection. Transplantation 94(12):1236–1242CrossRefPubMedGoogle Scholar
  41. Nucci AM et al (2002a) Long-term nutritional outcome after pediatric intestinal transplantation. J Pediatr Surg 37(3):460–463CrossRefPubMedGoogle Scholar
  42. Nucci AM et al (2002b) Enteral formula use in children after small bowel transplant. Nutr Clin Pract 17(2): 113–117CrossRefPubMedGoogle Scholar
  43. Nucci AM et al (2003) Serum growth factors and growth indices pre- and post-pediatric intestinal transplantation. J Pediatr Surg 38(7):1043–1047CrossRefPubMedGoogle Scholar
  44. Oh PL et al (2012) Characterization of the ileal microbiota in rejecting and nonrejecting recipients of small bowel transplants. Am J Transplant 12(3):753–762CrossRefPubMedGoogle Scholar
  45. Ojo AO et al (2003) Chronic renal failure after transplantation of a nonrenal organ. N Engl J Med 349(10): 931–940CrossRefPubMedGoogle Scholar
  46. Ordonez F et al (2013) Intestinal absorption rate in children after small intestinal transplantation. Am J Clin Nutr 97(4):743–749CrossRefPubMedGoogle Scholar
  47. Quintini C et al (2006) Analysis of risk factors for the development of post-transplant lymphoprolipherative disorder among 119 children who received primary intestinal transplants at a single center. Transplant Proc 38(6):1755–1758CrossRefPubMedGoogle Scholar
  48. Quiros-Tejeira RE et al (2004) Long-term parenteral nutritional support and intestinal adaption in children with short bowel syndrome: a 25-year experience. J Pediatr 145(2):157–163CrossRefPubMedGoogle Scholar
  49. Ramos E et al (2013) Post-transplant lympoproiferative disorders and other malignancies after pediatric intestinal transplantation: incidence, clinical features and outcome. Pediatr Transplant 17(5):472–478CrossRefPubMedGoogle Scholar
  50. Rivera JA et al (1998) Zinc supplementation improves the growth of stunted rural Guantemalan infants. J Nutr 128(3):556–562CrossRefPubMedGoogle Scholar
  51. Rothbaum RJ (1996) Complications of pediatric endoscopy. Gastrointest Enndosc Clin N Am 6(2):445–459Google Scholar
  52. Ruiz P et al (2004) Histological criteria for the identification of acute cellular rejection in human small bowl allografts: results of the pathology workshop at the VIII international small bowel transplant symposium. Transplant Proc 36(2):335–337CrossRefPubMedGoogle Scholar
  53. Ruiz P et al (2010) International grading scheme for acute cellular rejection in small-bowel transplantation: single-center experience. Transplant Proc 42(1):47–53CrossRefPubMedGoogle Scholar
  54. Ruz M et al (1997) A 14-mo zinc-supplementation trial in apparently healthy Chilean preschool children. Am J Clin Nutr 66(6):1406–1413CrossRefPubMedGoogle Scholar
  55. Sigurdsson L et al (1998a) Endoscopies in pediatric small intestinal transplant recipients: five years experience. Am J Gastroenterol 93(2):207–211CrossRefPubMedGoogle Scholar
  56. Sigurdsson L et al (1998b) Anatomic variability of rejection in intestinal allografts after pediatric intestinal transplantation. J Pediatr Gastroenterol Nutr 27(4): 403–406CrossRefPubMedGoogle Scholar
  57. Silva JT et al (2016) Infectious complications following small bowel transplantation. Am J Transplant 16(3): 951–959CrossRefPubMedGoogle Scholar
  58. Strohm S et al (1999) Nutrition management in pediatric small bowel transplant. Nutr Clin Pract 14:58–63CrossRefGoogle Scholar
  59. Sudan DL et al (2000) Assessment of function, growth and development, and long-term quality of life after small bowel transplantation. Transplant Proc 32(6): 1211–1212CrossRefPubMedGoogle Scholar
  60. Sudan D et al (2007) Calprotectin: a novel noninvasive marker for intestinal allograft monitoring. Ann Surg 246(2):311–315CrossRefPubMedPubMedCentralGoogle Scholar
  61. Sun Y et al (2010) Plasma nitrite and nitrate levels as a noninvasive marker of pathology after human small bowel transplantation. Transplantation 89(3):307–311CrossRefPubMedGoogle Scholar
  62. Ubesie AC et al (2013) Micronutrient deficiencies in pediatric and young adult intestinal transplant patients. Pediatr Transplant 17(7):638–645PubMedPubMedCentralGoogle Scholar
  63. Venick RS et al (2006) Nutritional outcomes following pediatric intestinal transplantation. Transplant Proc 38(6):1718–1719CrossRefPubMedGoogle Scholar
  64. Venick RS et al (2011) Long-term nutrition and predictors of growth and weight gain following pediatric intestinal transplantation. Transplantation 92(9):1058–1062PubMedGoogle Scholar
  65. Venick RS, Kositamongkol P, Wozniak LJ (2012) Prophylatic and pre-emptive therapies using ganciclovir and CMV immunoglobulin result in a significant reduction of CMV disease after intestinal transplantation. Oral Presentation. International Congress of the Transplantation Society, Berlin, Germany 2012Google Scholar
  66. Watson MJ et al (2008) Renal function impacts outcomes after intestinal transplantation. Transplantation 86(1): 117–122CrossRefPubMedGoogle Scholar
  67. Wozniak LJ et al (2014) Utility of an immune cell function assay to differentiate rejection from infectious enteritis in pediatric intestinal transplant recipients. Clin Transpl 28(2):229–235CrossRefGoogle Scholar
  68. Wozniak L et al. (2015) Why the surge in PTLD? An update on PTLD following intestinal transplantation. Oral Presentation. International Small Bowel Transplant Symposium. Buenos Aires, Argentina 2015Google Scholar
  69. Wu T et al (2003) A schema for histologic grading of small intestine allograft acute rejection. Transplantation 75(8):1241CrossRefPubMedGoogle Scholar
  70. Yeh J et al (2015) Endoscopy following pediatric intestinal transplant. J Pediatr Gastroenterol Nutr 61(6):636–640CrossRefPubMedPubMedCentralGoogle Scholar
  71. Zambernardi A et al (2014) Immunosuppressive therapies after intestinal transplant modulate the expression of Th1 signature genes during acute cellular rejection. Implications in the search for rejection biomarkers. Clin Transpl 28(12):1365–1371CrossRefGoogle Scholar
  72. Ziring D et al (2005) Infectious enteritis after intestinal transplantation: incidence, timing, and outcome. Transplantation 79(6):702–709CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.David Geffen School of MedicineLos AngelesUSA

Section editors and affiliations

  • George Mazariegos
    • 1
  • Dale Zecca
    • 2
  • Jennifer Melvin
    • 3
  1. 1.Hillman Center for Pediatric TransplantationChildren’s Hospital of Pittsburgh of UPMCPittsburghUSA
  2. 2.Children’s Hospital of PittsburghPittsburghUSA
  3. 3.Children’s Hospital of PittsburghPittsburghUSA

Personalised recommendations