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Table of Contents
CASE REPORT
Year : 2021  |  Volume : 15  |  Issue : 4  |  Page : 361-363

Early-onset inflammatory bowel disease after renal transplantation - A case report


Department of Nephrology and Gastroenterology, Kauvery Hospital, Chennai, Tamil Nadu, India

Date of Submission28-Nov-2020
Date of Decision20-Jul-2021
Date of Acceptance01-Sep-2021
Date of Web Publication30-Dec-2021

Correspondence Address:
Dr. Balaji Kirushnan
Kauvery Hospital, 199, Luz Church Road, Mylapore, Chennai - 600 004, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijot.ijot_145_20

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  Abstract 

Inflammatory bowel disease (IBD) is rarity after renal transplantation. Immunosuppressive therapy forms the cornerstone for the treatment of IBD. Ideally, IBD should not occur in this immunosuppressive state. However, local activation and dysregulation in the mucosal immune system has been proposed after tacrolimus and mycophenolate after renal transplantation. Our case report describes a very early-onset IBD after renal transplant which is hardly reported in literature.

Keywords: High tacrolimus level, renal transplant, ulcerative colitis


How to cite this article:
Kirushnan B, Raju B, Kumaran V. Early-onset inflammatory bowel disease after renal transplantation - A case report. Indian J Transplant 2021;15:361-3

How to cite this URL:
Kirushnan B, Raju B, Kumaran V. Early-onset inflammatory bowel disease after renal transplantation - A case report. Indian J Transplant [serial online] 2021 [cited 2022 Aug 10];15:361-3. Available from: https://www.ijtonline.in/text.asp?2021/15/4/361/334423




  Introduction Top


Inflammatory bowel disease (IBD) has been reported in a number of series following solid and hematopoietic transplants. In solid organ transplants, it has been seen following liver and renal transplantation. The primary pathogenesis seems unclear, as posttransplantation period is an immunosuppressed state and IBD seems to arise due to aberrant local immune system which should be suppressed in this scenario due to immunosuppressants. Previous case reports associate mycophenolate mofetil (MMF) as a promoter of IBD in posttransplant patients.[1] Tacrolimus level has also been reported to be associated with inflammatory colitis, usually seen months or years after transplant. Our case scenario is more unique in that the patient had a very early onset (<6 months) of IBD after transplant. Although we could not demonstrate a casual association between high tacrolimus level and IBD, diarrhea associated with high tacrolimus could be postulated in the etiopathogenesis of IBD by exposing the subepithelial antigens.


  Case Report Top


A 36-year-old male patient, a chronic smoker, was evaluated by the nephrologist for the first time when he and creatinine of 3.0 mg% in 2018. He was found to have hypertension in 2018. Urine routine showed albumin 1+ with no red blood cell (RBC). Ultrasound (USG) of the abdomen showed bilateral contracted kidneys. Renal Doppler showed no significant renal artery stenosis. ANA, dsDNA, and ANCA were negative. He was diagnosed with chronic interstitial nephritis with chronic kidney disease V. He was dialysis dependent by July 2019 and was on hemodialysis through arteriovenous fistula. He had received 2 units of packed RBCs. He was planned for live-related renal transplant with his spouse as a donor. Both were B positive. HLA showed 1/6 match. Complement dependent cytotoxicity crossmatch was negative. Flow cytometry crossmatch was not done. Donor-specific antibodies by Luminex were positive for Class I (4989 MFI) and Class II (6420 MFI). Tacrolimus genotyping was done and it was 2/3 (intermediate metabolizer). He received triple immunosuppression (prednisolone 10 mg once a day, tablet mycophenolate 500 mg twice a day, and tablet tacrolimus 1 mg twice a day) 2 weeks before transplant. He received rituximab 500 mg 2 weeks before the transplant. He received 3 sessions of 2.5 L plasma exchange on day 7, day 5, and day 1 before renal transplantation. DSA by Luminex before surgery was Class I 987 and Class II 1156. He was taken up for renal transplantation on January 07, 2020, with injection antithymocyte globulins 50 mg intravenous as an induction agent. There was no hyperacute rejection visible. He had a normal posttransplant course with normal renal functions by day 4. USG transplant kidney Doppler showed resistive index of 0.8. tacrolimus level on day 4 was 14 ng/ml. Dose of tacrolimus was reduced from 4 mg twice a day to 3 mg twice a day. He developed mild wound infection which responded to amoxicillin–clavulanic acid 625 mg twice a day for 5 days and daily dressings. He had normal renal functions till 4th month post transplant. He had creatinine of 1.5 on routine follow-up. He had developed new-onset diabetes mellitus after transplant which was managed appropriately. Tacrolimus level was 29 ng/ml. He had a history of diarrhea. Dose of tacrolimus was reduced to 2 mg twice a day. Creatinine normalized in 1 week and repeat tacrolimus level was 7.2 ng/ml. Stool routine was normal. Cytomegalovirus (CMV) DNA qualitative PCR (polymerase chain reaction) was negative. He developed bleeding per rectum on 6th month postrenal transplant. Stool routine showed no evidence of pus cells or mucus or ova or cyst. Per rectal examination did not show hemorrhoids or fissure. He was not on antiplatelets postrenal transplant. Routine tacrolimus level monitoring revealed a tacrolimus level of 10.4 ng/ml. Creatinine was 1.4 mg%. USG of transplant kidney showed normal Doppler indices. Tacrolimus dose was further reduced to 1 mg/day. He was seen by a medical gastroenterologist. Sigmoidoscopy was done which showed proctitis with sigmoid colitis [Figure 1]. Mucosal biopsy showed features of ulcerative colitis. There were no inclusion bodies by microscopy, and hence, CMV DNA PCR in the intestinal biopsy sample was not done. Diagnosis of IBD predominantly ulcerative colitis was made. Mesalamine was started in a dose of 800 mg twice a day. Bleeding PR subsided after 1 month. Repeat sigmoidoscopy showed healing areas of the inflammation with no new areas of ulceration seen [Figure 2] and [Figure 3]. The patient is currently on tablet prednisolone 10 mg once a day, tablet tacrolimus 0.5 mg twice a day, and tablet MMF 500 mg twice a day. Mesalamine was stopped after 1 month and was not introduced later.
Figure 1: Active lesions in the sigmoid colon 1

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Figure 2: Fibrosed lesions in the sigmoid colon

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Figure 3: Healed lesions in the sigmoid colon

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  Discussion Top


The incidence of gastrointestinal complications in renal transplantation is relatively high, ranging around 20%.[1] Severe complications can lead to patient death or it can lead to graft loss.[2] Complications include oral lesions, esophagitis, peptic ulcer, diarrhea, colonic hemorrhage, or perforation. Diarrhea is a very common complication after renal transplant and varies from mild to moderate intensity across various groups.[3] The reasons for the above could be due to medications, infections, or malignancy. Immunosuppressive medications have also been implicated in about 34% to cause diarrhea.[4] The role of the latter remains controversial as an analysis from 16 transplantation centers in Belgium questioned a dominant position of immunosuppressive therapy-associated severe diarrhea in renal transplant patients.[3] Colonic complications after renal transplant have been reported. Colonic bleeds and perforation are common in patients with polycystic kidney disease.[5] CMV infection can present with ascending and descending colon hemorrhage and ischemic colitis leading to perforation.[6]

IBDs after transplants are a rarity and have ill-defined etiologies for it.[7] The treatments for IBD are immunosuppressive medications which renal transplant patients are already on, hence making it difficult to understand and comprehend. Passfall et al. in 1992 reported the first case of ulcerative colitis in a kidney transplant recipient 6 years after the date of transplant while the patient was on cyclosporine monotherapy.[8] Calcineurin inhibitors inhibit the peptidyl-prolyl isomerase enzyme activity and interfere with effective T-cell intracellular signaling. In genetically predisposed individuals, CNIs may lead to reduction of the CD8 suppressor cells to a greater degree than other T-cell populations, increasing the helper-to-suppressor ratio. This has been hypothesized to be the etiological factor in IBD according to some studies.[9] Tacrolimus, on the other hand, has also been used as a rescue therapy in refractory cases of ulcerative colitis.[10] MMF has also been described to be associated with IBD in many case series.[11] MMF dose reduction has been shown to be helpful in these patients but with an increased risk of rejection. In other patients, MMF had been continued with successful control of IBD after 6 months.[1] These reports suggest that although a sufficient degree of allograft immune tolerance had been achieved, selective autoimmunity did occur in other regional areas like the colon.[12]

In the series described by Riley et al., all patients presented many years after transplant (>6 years), and one of the reasons postulated by the authors was a reduction in immunosuppression after many years of renal transplant.[7] Our patient was unique as we report a very early incidence of de novo ulcerative colitis after renal transplant. There were no changes in the dose of mycophenolate of this patient from the time of transplant. However, this patient had a high tacrolimus level. The possible association of high tacrolimus level inducing chronic diarrhea exposing the subepithelial antigens to local immune system initiating auto-immunity has been proposed. Further studies are needed to ascertain the casual role of tacrolimus and de novo ulcerative colitis.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Maes BD, Dalle I, Geboes K, Oellerich M, Armstrong VW, Evenepoel P, et al. Erosive enterocolitis in mycophenolate mofetil-treated renal-transplant recipients with persistent afebrile diarrhea. Transplantation 2003;75:665-72.  Back to cited text no. 1
    
2.
Hardinger KL, Brennan DC, Lowell J, Schnitzler MA. Long-term outcome of gastrointestinal complications in renal transplant patients treated with mycophenolate mofetil. Transpl Int 2004;17:609-16.  Back to cited text no. 2
    
3.
Maes B, Hadaya K, de Moor B, Cambier P, Peeters P, de Meester J, et al. Severe diarrhea in renal transplant patients: Results of the DIDACT study. Am J Transplant 2006;6:1466-72.  Back to cited text no. 3
    
4.
Sarkio S, Halme L, Kyllönen L, Salmela K. Severe gastrointestinal complications after 1,515 adult kidney transplantations. Transpl Int 2004;17:505-10.  Back to cited text no. 4
    
5.
Domínguez Fernández E, Albrecht KH, Heemann U, Kohnle M, Erhard J, Stöblen F, et al. Prevalence of diverticulosis and incidence of bowel perforation after kidney transplantation in patients with polycystic kidney disease. Transpl Int 1998;11:28-31.  Back to cited text no. 5
    
6.
Lee CJ, Lian JD, Chang SW, Chou MC, Tyan YS, Wong LC, et al. Lethal cytomegalovirus ischemic colitis presenting with fever of unknown origin. Transpl Infect Dis 2004;6:124-8.  Back to cited text no. 6
    
7.
Riley TR, Schoen RE, Lee RG, Rakela J. A case series of transplant recipients who despite immunosuppression developed inflammatory bowel disease. Am J Gastroenterol 1997;92:279-82.  Back to cited text no. 7
    
8.
Passfall J, Distler A, Riecken EO, Zeitz M. Development of ulcerative colitis under the immunosuppressive effect of cyclosporine. Clin Investig 1992;70:611-3.  Back to cited text no. 8
    
9.
Hoang P, Senju M, Lowes JR, Jewell DP. Phenotypic characterization of isolated intraepithelial lymphocytes in patients with ulcerative colitis and normal controls. Dig Dis Sci 1992;37:1725-8.  Back to cited text no. 9
    
10.
Nakase H, Mikami S, Matsuura M, Ueno S, Uza N, Inoue S, et al. Rescue therapy with tacrolimus for a patient with severe ulcerative colitis refractory to combination leukocytapheresis and high-dose corticosteroid therapy. Intern Med 2007;46:717-20.  Back to cited text no. 10
    
11.
Dalle IJ, Maes BD, Geboes KP, Lemahieu W, Geboes K. Crohn's-like changes in the colon due to mycophenolate? Colorectal Dis 2005;7:27-34.  Back to cited text no. 11
    
12.
Ramji A, Owen DA, Erb SR, Scudamore CH, Yoshida EM. Post-liver transplant Crohn's disease: Graft tolerance but not self-tolerance? Dig Dis Sci 2002;47:522-7.  Back to cited text no. 12
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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