Letter to the Editor Open Access
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Transplant. Feb 18, 2022; 12(2): 21-23
Published online Feb 18, 2022. doi: 10.5500/wjt.v12.i2.21
Immunosuppressive regimens and outcomes of inflammatory bowel disease patients requiring kidney transplantation
Urvashi Singh, Department of Surgery, Wythenshawe Hospital, Manchester University Hospitals NHS Foundation Trust, Manchester M23 9LT, United Kingdom
Baljit Singh, Department of Colorectal Surgery, University Hospitals Leicester, Leicester LE1 5WW, United Kingdom
Maria Irene Bellini, Department of Surgical Sciences, Sapienza University, Roma 00161, Italy
ORCID number: Urvashi Singh (0000-0003-2176-5750); Baljit Singh (0000-0001-9713-0247); Maria Irene Bellini (0000-0003-0730-4923).
Author contributions: Singh B and Bellini MI designed the study, provided guidance regarding inflammatory bowel disease and kidney transplantation respectively and proofread the manuscript before submission; Singh U performed literature review and wrote manuscript; all authors have read and approve the final manuscript.
Conflict-of-interest statement: There is no conflict of interest to be declared by any of the authors.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Urvashi Singh, MBBS, MSc, Department of Surgery, Wythenshawe Hospital, Manchester University Hospitals NHS Foundation Trust, Southmoor Road, Manchester M23 9LT, United Kingdom. usingh01@qub.ac.uk
Received: October 5, 2021
Peer-review started: October 5, 2021
First decision: December 16, 2021
Revised: December 28, 2021
Accepted: January 20, 2022
Article in press: January 20, 2022
Published online: February 18, 2022
Processing time: 127 Days and 17 Hours

Abstract

Patients with inflammatory bowel disease (IBD) can develop extra-renal complications and as a result, suffer from end stage renal failure requiring kidney transplantation (KT). A brief review of available literature revealed that IBD patients undergoing KT have shorter overall survival rates compared to their controls. Literature reporting steroid regimens and survival outcomes specific to IBD and post kidney transplant are scarce and these studies have small sample sizes thus making it difficult to draw accurate conclusions. Further research is required in the form of a randomized controlled study to clarify the effect and mechanism of steroid immunosuppression on the prognosis of renal transplant recipients and explore new treatment schemes.

Key Words: Inflammatory bowel disease; Kidney transplantation; Steroids; Immunosuppression; Kidney failure; Ulcerative colitis; Crohn’s disease

Core Tip: Patients with inflammatory bowel disease (IBD) can develop extra-renal complications and as a result, suffer from end stage renal failure requiring kidney transplantation (KT). A brief review of available literature revealed that IBD patients undergoing KT have shorter overall survival rates compared to their controls. We highlight through our paper, previously reported survival outcomes and immunosuppressive regimens used in this cohort of patients through a brief literature review.



TO THE EDITOR

The recent systematic review published by Aref et al[1] titled ‘Does steroid-free immunosuppression improve the outcome in kidney transplant recipients compared to conventional protocols?’ provided thought provoking insight into the impact of steroid-free immunosuppression on the outcome of kidney transplant recipients. Further to the authors conclusions in their paper, we aim to highlight the effect of steroids and steroid free regimens on the outcomes of inflammatory bowel disease (IBD) patients who were kidney transplant receipts.

IBD is comprised of Crohn’s disease (CD) and ulcerative colitis (UC). Patients with IBD can develop extra-intestinal manifestations. These include peripheral arthritis, oral aphthous ulcers, erythema nodosum, episcleritis, pyoderma gangrenosum, primary sclerosing cholangitis and uveitis[2]. Patients with IBD can develop renal manifestations of the disease, including nephrolithiasis, glomerulonephritis, tubulointerstitial nephritis, and secondary amyloidosis[3]. A study reported that the incidence of end stage renal disease (ESRD) in patients with CD was 5 times higher than cross matched controls[3]. Kidney injury can also result from dehydration, long term malnutrition and side effects of IBD medical therapy. These can all contribute to chronic kidney disease and eventually ESRD warranting kidney dialysis and transplantation[3].

Studies reporting IBD patients requiring kidney transplantation (KT) are scarce. However, existing literature discussing IBD, and post KT outcomes reports similar survival rates for IBD patients post transplantation. In a recent detailed study, in which 12 IBD patients (7 CD patients and 5 UC patients) underwent KT due to immunoglobulin A (IgA) nephropathy and polycystic kidney disease, the estimated survival of IBD patients was reported to be 80.8% vs 96.8% in patients without IBD (P = 0.001)[4]. Treatment with infliximab or a dalimumab resulted in stable disease or improvement in kidney transplant patients affected by mild to moderate IBD. Eleven out of 12 patients were on maintenance immunosuppression with low dose corticosteroids (5 mg prednisolone daily), calcineurin inhibitors (tacrolimus), and anti-metabolite (mycophenolic acid in nine and mycophenolate mofetil in two); the twelfth patient was kept on low-dose corticosteroids and tacrolimus only. IBD course remained stable in the whole transplant group, but resulted in an increased risk of mortality and hospitalization, due to a higher infection rate[4].

Data on immunosuppression and steroid regimens specific to IBD and the post-KT period remains poorly reported. In a study, six patients (5 CD patients and 1 UC patient) out of 1537 patients with IBD, underwent KT for kidney failure secondary to amyloidosis, IgA nephropathy, oxalate nephropathy, haemolytic uraemic syndrome, and chronic kidney failure of unknown origin[5]. Five of the six patients received steroid therapy after transplantation, yet specific immunosuppressive regimens are not reported pre and post transplantation. The study discusses the outcomes of IBD patients post liver transplantation together with KT, hence it is not possible to comment on the post KT alone. However, the study does report an 84% survival rate during a total follow up of 103.0 mo and median follow up of 33 mo after solid organ transplantation. One male patient also developed papillary renal cell carcinoma in the transplanted kidney in this study. No graft rejection was reported[5]. In a different prospective cohort study that followed 26 patients with IBD and systemic ascorbic acid (AA) amyloidosis between 1989 and 2010, an 83% survival rate 15 years post transplantation was reported. In this study all patients had renal dysfunction as result of AA amyloidosis[6]. However, only six patients required renal transplantation due to ESRD. Four patients had deceased donor transplants and two patients had live-related transplants. There were five functioning grafts at census 0.8, 3.2, 4.2, 20.1 and 24.6 years after transplantation. One graft failure was reported at 14.5 years after renal transplantation due to recurrence of amyloidosis and sustained chronic inflammatory activity. The study notes that patients were provided with steroid regimens however does not provide specific details about whether these regimens were supplemented with other immunosuppressants[6]. Specific reporting regarding immunosuppressive regimens is warranted for IBD patients before and after KT.

In conclusion, IBD is an immunomediated disease that is associated with kidney disease and can cause ESRD in patients. From the available literature, it is suggested that patients with IBD that undergo KT have shorter overall survival rates compared to their controls. Reported data is scarce and inconclusive due to the small patient cohort sizes. Further research is required in the form of a randomized controlled study to clarify the effect and mechanism of steroid immunosuppression on the prognosis of renal transplant recipients and explore new treatment schemes.

Footnotes

Provenance and peer review: Invited article; Externally peer reviewed.

Peer-review model: Single blind

Specialty type: Transplantation

Country/Territory of origin: United Kingdom

Peer-review report’s scientific quality classification

Grade A (Excellent): 0

Grade B (Very good): B

Grade C (Good): C, C

Grade D (Fair): D

Grade E (Poor): 0

P-Reviewer: Gisbert JP, Velikova TV, Zhou Y S-Editor: Wang JJ L-Editor: A P-Editor: Wang JJ

References
1.  Aref A, Sharma A, Halawa A. Does steroid-free immunosuppression improve the outcome in kidney transplant recipients compared to conventional protocols? World J Transplant. 2021;11:99-113.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in CrossRef: 3]  [Cited by in F6Publishing: 3]  [Article Influence: 1.0]  [Reference Citation Analysis (2)]
2.  Annese V. A Review of Extraintestinal Manifestations and Complications of Inflammatory Bowel Disease. Saudi J Med Med Sci. 2019;7:66-73.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 25]  [Cited by in F6Publishing: 26]  [Article Influence: 5.2]  [Reference Citation Analysis (0)]
3.  Park S, Chun J, Han KD, Soh H, Choi K, Kim JH, Lee J, Lee C, Im JP, Kim JS. Increased end-stage renal disease risk in patients with inflammatory bowel disease: A nationwide population-based study. World J Gastroenterol. 2018;24:4798-4808.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in CrossRef: 41]  [Cited by in F6Publishing: 43]  [Article Influence: 7.2]  [Reference Citation Analysis (0)]
4.  Grupper A, Schwartz D, Baruch R, Schwartz IF, Nakache R, Goykhman Y, Katz P, Lebedinsky A, Nachmany I, Lubezky N, Aouizerate J, Shashar M, Katchman H. Kidney transplantation in patients with inflammatory bowel diseases (IBD): analysis of transplantation outcome and IBD activity. Transpl Int. 2019;32:730-738.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 9]  [Cited by in F6Publishing: 13]  [Article Influence: 2.6]  [Reference Citation Analysis (0)]
5.  Schnitzler F, Friedrich M, Stallhofer J, Schönermarck U, Fischereder M, Habicht A, Karbalai N, Wolf C, Angelberger M, Olszak T, Beigel F, Tillack C, Göke B, Zachoval R, Denk G, Guba M, Rust C, Grüner N, Brand S. Solid Organ Transplantation in Patients with Inflammatory Bowel Diseases (IBD): Analysis of Transplantation Outcome and IBD Activity in a Large Single Center Cohort. PLoS One. 2015;10:e0135807.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 23]  [Cited by in F6Publishing: 24]  [Article Influence: 2.7]  [Reference Citation Analysis (0)]
6.  Sattianayagam PT, Gillmore JD, Pinney JH, Gibbs SD, Wechalekar AD, Gilbertson JA, Rowczenio D, Hawkins PN, Lachmann HJ. Inflammatory bowel disease and systemic AA amyloidosis. Dig Dis Sci. 2013;58:1689-1697.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 25]  [Cited by in F6Publishing: 24]  [Article Influence: 2.2]  [Reference Citation Analysis (0)]