1
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Kizilbash SJ, Jensen CJ, Kouri AM, Balani SS, Chavers B. Steroid avoidance/withdrawal and maintenance immunosuppression in pediatric kidney transplantation. Pediatr Transplant 2022; 26:e14189. [PMID: 34786800 DOI: 10.1111/petr.14189] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Revised: 09/30/2021] [Accepted: 10/06/2021] [Indexed: 12/17/2022]
Abstract
BACKGROUND Corticosteroids have been an integral part of maintenance immunosuppression for pediatric kidney transplantation. However, prolonged steroid therapy is associated with significant toxicities resulting in several SW/avoidance strategies in recent years. METHOD/OBJECTIVE This comprehensive review aims to discuss steroid-related toxicities and the safety, efficacy, and benefit of steroid avoidance/withdrawal immunosuppression in pediatric kidney transplant recipients. RESULTS Initial studies of SW/avoidance conducted in the setting of CSA and AZA showed an increased incidence of AR but no increase in graft loss or mortality with SW/avoidance maintenance immunosuppression. Studies performed under modern immunosuppression (induction therapy, Tac, and MMF) show no significant increase in AR or graft loss with SW/avoidance immunosuppression. Furthermore, SW/avoidance immunosuppression is associated with significant improvement in growth, BMI, BP control, and lipid profile in pediatric kidney transplant recipients. Despite these data, SW/avoidance remains controversial, and only 40% of pediatric kidney transplant recipients in the United States are currently on SW/avoidance maintenance immunosuppression. CONCLUSION SW/avoidance maintenance immunosuppression is safe and associated with fewer side effects compared with steroid-inclusive maintenance immunosuppression in pediatric kidney transplant recipients.
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Affiliation(s)
- Sarah J Kizilbash
- Pediatric Nephrology, University of Minnesota, Minneapolis, Minnesota, USA
| | - Chelsey J Jensen
- Solid Organ Transplant, University of Minnesota, Minneapolis, Minnesota, USA
| | - Anne M Kouri
- Pediatric Nephrology, University of Minnesota, Minneapolis, Minnesota, USA
| | - Shanthi S Balani
- Pediatric Nephrology, University of Minnesota, Minneapolis, Minnesota, USA
| | - Blanche Chavers
- Pediatric Nephrology, University of Minnesota, Minneapolis, Minnesota, USA
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2
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Panel-reactive Antibody and the Association of Early Steroid Withdrawal With Kidney Transplant Outcomes. Transplantation 2022; 106:648-656. [PMID: 33826598 PMCID: PMC8490476 DOI: 10.1097/tp.0000000000003777] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Early steroid withdrawal (ESW) is a viable maintenance immunosuppression strategy in low-risk kidney transplant recipients. A low panel-reactive antibody (PRA) may indicate low-risk condition amenable to ESW. We aimed to identify the threshold value of PRA above which ESW may pose additional risk and to compare the association of ESW with transplant outcomes across PRA strata. METHODS We studied 121 699 deceased-donor kidney-only recipients in 2002-2017 from Scientific Registry of Transplant Recipients. Using natural splines and ESW-PRA interaction terms, we explored how the associations of ESW with transplant outcomes change with increasing PRA values and identified a threshold value for PRA. Then, we assessed whether PRA exceeding the threshold modified the associations of ESW with 1-y acute rejection, death-censored graft failure, and death. RESULTS The association of ESW with acute rejection exacerbated rapidly when PRA exceeded 60. Among PRA ≤60 recipients, ESW was associated with a minor increase in rejection (adjusted odds ratio [aOR], 1.001.051.10) and with a tendency of decreased graft failure (adjusted hazard ratio [aHR], 0.910.971.03). However, among PRA >60 recipients, ESW was associated with a substantial increase in rejection (aOR, 1.191.271.36; interaction P < 0.001) and with a tendency of increased graft failure (aHR, 0.981.081.20; interaction P = 0.028). The association of ESW with death was similar between PRA strata (PRA ≤60, aHR, 0.910.961.01; and PRA >60, aHR, 0.900.991.09; interaction P = 0.5). CONCLUSIONS Our findings show that the association of ESW with transplant outcomes is less favorable in recipients with higher PRA, especially those with PRA >60, suggesting a possible role of PRA in the risk assessment for ESW.
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3
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Nicholson ML, Hoff M, Leighton P, Mohamed I, Hosgood SA. Pre-emptive immunosuppression using tacrolimus monotherapy does not reduce the rate of early acute rejection in renal transplantation from live donors: a comparative cohort study. Transpl Int 2020; 33:1754-1761. [PMID: 32964465 DOI: 10.1111/tri.13747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 08/04/2020] [Accepted: 09/14/2020] [Indexed: 11/29/2022]
Abstract
The planned nature of live donor kidney transplantation allows for immunosuppression to be initiated in the pretransplant period. The aim of this study was to determine the effect of pre-emptive immunosuppression on acute rejection rates after live donor kidney transplantation. In two consecutive cohorts of live donor kidneys transplants, 99 patients received pre-emptive immunosuppression with tacrolimus monotherapy for 2 weeks prior to transplantation (PET group - first era) and 100 patients received tacrolimus-based immunosuppression commencing on the day of transplantation (control group - second era). The main outcome measure was the incidence of biopsy-proven acute rejection (BPAR) in the first 3 months post-transplantation. Tacrolimus levels were significantly higher in the PET group at day 4 post-transplant (PET 9.08 ± 4.57 vs. control 5.92 ± 3.64 ng/ml; P < 0.0001), but there were no significant differences in tacrolimus levels at day 7 (PET 8.22 ± 3.58 vs. control 7.63 ± 3.56 ng/ml; P = 0.2452). BPAR was numerically higher in the PET group, but this difference did not reach statistical significance (PET 13/99 vs. control 6/100; P = 0.097). There were no differences in allograft function measured by serum creatinine at 1 year (PET 130 ± 36 vs. control 142 ± 69 μmol/l; P = 0.6829). Graft survival at 1 year was equivalent in both groups (PET 96.9 vs. control 97.0%; P = 0.9915). This study suggests that there is little role for the use of pre-emptive tacrolimus monotherapy in ABO blood group and HLA-compatible live donor kidney transplantation in patients on triple maintenance immunosuppression.
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Affiliation(s)
- Michael L Nicholson
- Department of Surgery, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.,Leicester General Hospital, University of Leicester, Leicester, UK
| | - Mekhola Hoff
- Department of Surgery, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK
| | - Philippa Leighton
- Department of Surgery, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK
| | - Ismail Mohamed
- Leicester General Hospital, University of Leicester, Leicester, UK
| | - Sarah A Hosgood
- Department of Surgery, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK
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4
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Cho JM, Jun H, Jo HA, Han KH, Kim HS, Han SY. A case of successful late steroid withdrawal after ABO-incompatible kidney transplantation. KOREAN JOURNAL OF TRANSPLANTATION 2020; 34:121-125. [PMID: 35769349 PMCID: PMC9188928 DOI: 10.4285/kjt.2020.34.2.121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Revised: 06/04/2020] [Accepted: 06/10/2020] [Indexed: 11/24/2022] Open
Abstract
Few data exist regarding steroid withdrawal in ABO-incompatible (ABO-i) kidney transplantation (KT). Here, we report a case of steroid withdrawal after ABO-i KT. A 46-year-old man diagnosed with Henoch-Schonlein purpura received ABO-i KT from his 42-year-old sister. The recipient and donor blood types were O and AB, respectively. His preoperative ABO antibody titers were anti-A of 1:16 and anti-B of 1:8 in isoagglutinin test. HLA mismatch was 0 and he received a single 325 mg/m2 dose of intravenous (IV) rituximab 4 weeks before KT. Three sessions of plasma exchange were undertaken before KT and low-dose IV immunoglobulin of 0.1 g/kg was administered after plasma exchange. On the day of the operation, ABO antibody titer decreased to anti-A of 1:4 and anti-B of 1:2. Renal function remained stable after KT. The patient wished to stop steroid treatment despite the risk of rejection after withdrawal. Steroid tapering was initiated at 20 months and accomplished at 26 months after KT. At that time, serum creatinine level was 1.13 mg/dL, and anti-A and anti-B titers were 1:8 and 1:2, respectively. No issues were observed after steroid withdrawal. At 48 months after KT, serum creatinine level was 1.21 mg/dL, and anti-A and anti-B antibody titers were 1:32 and 1:2, respectively. Steroid withdrawal in ABO-i KT might be considered in immunologically low-risk patients.
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Affiliation(s)
- Jeong Min Cho
- Department of Internal Medicine, Inje University College of Medicine, Ilsan Paik Hospital, Goyang, Korea
| | - Heungman Jun
- Department of Surgery, Inje University College of Medicine, Ilsan Paik Hospital, Goyang, Korea
| | - Hyung Ah Jo
- Department of Internal Medicine, Inje University College of Medicine, Ilsan Paik Hospital, Goyang, Korea
| | - Kum Hyun Han
- Department of Internal Medicine, Inje University College of Medicine, Ilsan Paik Hospital, Goyang, Korea
| | - Han-Seong Kim
- Department of Pathology, Inje University College of Medicine, Ilsan Paik Hospital, Goyang, Korea
| | - Sang Youb Han
- Department of Internal Medicine, Inje University College of Medicine, Ilsan Paik Hospital, Goyang, Korea
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5
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Sethi SK, Bansal SB, Wadhwani N, Tiwari A, Arora D, Sharma R, Nandwani A, Yadav DK, Mahapatra AK, Jain M, Jha P, Ghosh P, Bhan A, Dhaliwal M, Raghunathan V, Kher V. Pediatric ABO-incompatible kidney transplantation: Evolving with the advancing apheresis technology: A single-center experience. Pediatr Transplant 2018; 22:e13138. [PMID: 29380556 DOI: 10.1111/petr.13138] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/28/2017] [Indexed: 12/11/2022]
Abstract
Recent literature has endorsed favorable outcomes following ABOi kidney transplantation in pediatric population. Nevertheless, reluctance to pursue an ABOi still remains pervasive. This could be ascribed to various legitimate reasons, namely less extensive pediatric ABOi data, technical difficulties encountered during PP, cost restraints, and concerns regarding higher rates of antibody-mediated rejection, infectious complications, and post-transplant lymphoproliferative disorder as compared to adults. However, given the similar excellent outcomes of both ABOi and ABOc kidney transplantation, clinicians should consider this option sooner if a compatible donor or swap is not available. Here, we describe the outcomes of three pediatric ABOi performed at our institute in India (from 2014 till now), wherein distinct apheresis modalities had been employed in each desensitization protocol, and our techniques evolved with advancing science in apheresis. This case series includes India's first published pediatric ABO-incompatible transplant (Case 2) and the youngest child to undergo ABO-incompatible renal transplant in SAARC nations (Case 3).
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Affiliation(s)
- Sidharth Kumar Sethi
- Kidney and Renal Transplant Institute, Medanta, The Medicity Hospital, Gurgaon, India
| | - Shyam Bihari Bansal
- Kidney and Renal Transplant Institute, Medanta, The Medicity Hospital, Gurgaon, India
| | - Nikita Wadhwani
- Kidney and Renal Transplant Institute, Medanta, The Medicity Hospital, Gurgaon, India
| | - Aseem Tiwari
- Blood Transfusion Department, Medanta, The Medicity Hospital, Gurgaon, India
| | - Dinesh Arora
- Blood Transfusion Department, Medanta, The Medicity Hospital, Gurgaon, India
| | - Reetesh Sharma
- Kidney and Renal Transplant Institute, Medanta, The Medicity Hospital, Gurgaon, India
| | - Ashish Nandwani
- Kidney and Renal Transplant Institute, Medanta, The Medicity Hospital, Gurgaon, India
| | - Dinesh Kumar Yadav
- Kidney and Renal Transplant Institute, Medanta, The Medicity Hospital, Gurgaon, India
| | - Amit Kumar Mahapatra
- Kidney and Renal Transplant Institute, Medanta, The Medicity Hospital, Gurgaon, India
| | - Manish Jain
- Kidney and Renal Transplant Institute, Medanta, The Medicity Hospital, Gurgaon, India
| | - Pranaw Jha
- Kidney and Renal Transplant Institute, Medanta, The Medicity Hospital, Gurgaon, India
| | - Prasun Ghosh
- Urology Department, Medanta, The Medicity Hospital, Gurgaon, India
| | - Anil Bhan
- Cardiothoracic Surgery, Medanta, The Medicity Hospital, Gurgaon, India
| | - Maninder Dhaliwal
- Pediatric Critical Care, Medanta, The Medicity Hospital, Gurgaon, India
| | - Veena Raghunathan
- Pediatric Critical Care, Medanta, The Medicity Hospital, Gurgaon, India
| | - Vijay Kher
- Kidney and Renal Transplant Institute, Medanta, The Medicity Hospital, Gurgaon, India
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6
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Late Steroid Withdrawal Following AB0-Incompatible Renal Transplantation. Transplant Proc 2018; 50:72-78. [PMID: 29407335 DOI: 10.1016/j.transproceed.2017.12.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2017] [Accepted: 12/04/2017] [Indexed: 11/21/2022]
Abstract
BACKGROUND Current evidence on steroid withdrawal following AB0-incompatible (AB0i) renal transplantation is low. We compared clinical outcomes of patients who agreed to late steroid withdrawal and patients who remained on steroid treatment. METHODS Steroid withdrawal was carried out in 11 patients at ≥12 months after transplantation (group W). For comparison, we analyzed 19 patients who remained on triple immunosuppression including steroids (group M). Minimum follow-up was 24 months following transplantation and 12 months after steroid withdrawal. RESULTS Baseline characteristics, including observation times, were not different between groups W and M. Graft survival was 100% in group W compared with 84% (16/19) in group M (P = .15). In group M, 1 patient experienced graft failure because of suspected antibody-mediated rejection (ABMR) following temporary cessation of mycophenolate treatment after a diagnosis of cryptococcal pneumonia. Two patients died with functioning graft because of sepsis. In group W, we observed 1 episode of ABMR following steroid withdrawal. At the end of follow-up, estimated glomerular filtration rates (eGFR) were 54 (19-91) versus 60 (15-85) mL/min/1.73 m2 in group W versus M, respectively (P = .67). CONCLUSIONS Late steroid withdrawal following AB0i transplantation is feasible at a moderate risk of rejection. We recommend close monitoring of renal function and HLA antibodies during and after steroid withdrawal. On the other hand, the occurrence of severe infections causing death and graft loss in patients on triple maintenance immunosuppression including steroids should remind us to consider the overall immunosuppressive burden.
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7
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Novosel MK, Bistrup C. Discontinuation of steroids in ABO-incompatible renal transplantation. Transpl Int 2016; 29:464-70. [PMID: 26706618 DOI: 10.1111/tri.12735] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2015] [Revised: 10/12/2015] [Accepted: 12/16/2015] [Indexed: 12/16/2022]
Abstract
A steroid-free protocol for ABO-compatible renal transplantation has been used at our center since 1983. To minimize the adverse effects of steroids, we also developed a steroid sparing protocol for ABO-incompatible renal transplantation in 2008. The present study is a report of our results. A retrospective review of the first 50 ABO-incompatible renal transplantations performed at a single university center. If no immunological events occurred in the post-transplant period, prednisolone tapering was initiated approximately 3 months after transplantation. Forty-three patients completed prednisolone tapering after 289 ± 58 days. Three patients died during follow-up, and four patients lost graft function. None of these adverse events were rejection related. Eleven patients experienced rejections; seven were on prednisolone and four were after weaning from prednisolone. All patients responded well to antirejection treatment. Overall, 1-year rejection rate was 19%. One- and 3-year graft survival was 94% and 91%, respectively. One-year post-transplant median serum creatinine was 123 μmol/L. We found acceptable rejection rates, graft survival, and creatinine levels in patients undergoing ABO-incompatible renal transplantations with a steroid sparing protocol. However, a longer follow-up of a lager cohort is needed before firm conclusions can be made.
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Affiliation(s)
- Marija Kristina Novosel
- Division of Nephrology, Department of Medicine, Fredericia Hospital - Part of Lillebaelt Hospital, Fredericia, Denmark.,Department of Nephrology, Odense University Hospital, Odense, Denmark
| | - Claus Bistrup
- Department of Nephrology, Odense University Hospital, Odense, Denmark
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8
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Nijhoff MF, Engelse MA, Dubbeld J, Braat AE, Ringers J, Roelen DL, van Erkel AR, Spijker HS, Bouwsma H, van der Boog PJM, de Fijter JW, Rabelink TJ, de Koning EJP. Glycemic Stability Through Islet-After-Kidney Transplantation Using an Alemtuzumab-Based Induction Regimen and Long-Term Triple-Maintenance Immunosuppression. Am J Transplant 2016; 16:246-53. [PMID: 26288226 DOI: 10.1111/ajt.13425] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2015] [Revised: 06/01/2015] [Accepted: 06/21/2015] [Indexed: 01/25/2023]
Abstract
Pancreatic islet transplantation is performed in a select group of patients with type 1 diabetes mellitus. Immunosuppressive regimens play an important role in long-term islet function. We aimed to investigate the efficacy of islet transplantation in patients with type 1 diabetes and a previous kidney transplantation using an alemtuzumab-based induction regimen and triple maintenance immunosuppression. Patients with type 1 diabetes, who had received a kidney transplant previously, were treated with alemtuzumab as induction therapy for their first islet transplantation and basiliximab induction therapy for subsequent islet transplantations. Maintenance immunosuppression consisted of triple immunosuppression (tacrolimus, mycophenolate mofetil, and prednisolone). Thirteen patients (age 50.9 ± 9.2 years, duration of diabetes 35 ± 9 years) received a total of 22 islet transplantations. One- and 2-year insulin independence was 62% and 42%, respectively; graft function was 100% and 92%, respectively. HbA1c dropped from 57.2 ± 13.1 (7.4 ± 1.2%) to 44.5 ± 11.8 mmol/molHb (6.2 ± 0.9%) (p = 0.003) after 2 years. Six of 13 patients suffered from severe hypoglycemia before islet transplantation. After transplantation, severe hypoglycemia was restricted to the only patient who lost graft function. Creatinine clearance was unchanged. Islet-after-kidney transplantation in patients with type 1 diabetes using an alemtuzumab-based induction regimen leads to considerable islet allograft function and improvement in glycemic control.
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Affiliation(s)
- M F Nijhoff
- Department of Medicine, Division of Endocrinology and Metabolism, Leiden University Medical Centre, Leiden, the Netherlands.,Division of Nephrology and Transplantation, Leiden University Medical Centre, Leiden, the Netherlands
| | - M A Engelse
- Division of Nephrology and Transplantation, Leiden University Medical Centre, Leiden, the Netherlands
| | - J Dubbeld
- Departments of Surgery, Leiden University Medical Centre, Leiden, the Netherlands
| | - A E Braat
- Departments of Surgery, Leiden University Medical Centre, Leiden, the Netherlands
| | - J Ringers
- Departments of Surgery, Leiden University Medical Centre, Leiden, the Netherlands
| | - D L Roelen
- Immunohematology, Leiden University Medical Centre, Leiden, the Netherlands
| | - A R van Erkel
- Radiology, Leiden University Medical Centre, Leiden, the Netherlands
| | - H S Spijker
- Division of Nephrology and Transplantation, Leiden University Medical Centre, Leiden, the Netherlands
| | - H Bouwsma
- Division of Nephrology and Transplantation, Leiden University Medical Centre, Leiden, the Netherlands
| | - P J M van der Boog
- Division of Nephrology and Transplantation, Leiden University Medical Centre, Leiden, the Netherlands
| | - J W de Fijter
- Division of Nephrology and Transplantation, Leiden University Medical Centre, Leiden, the Netherlands
| | - T J Rabelink
- Division of Nephrology and Transplantation, Leiden University Medical Centre, Leiden, the Netherlands
| | - E J P de Koning
- Department of Medicine, Division of Endocrinology and Metabolism, Leiden University Medical Centre, Leiden, the Netherlands.,Division of Nephrology and Transplantation, Leiden University Medical Centre, Leiden, the Netherlands
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9
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Baek CH, Kim H, Yu H, Shin E, Cho H, Yang WS, Han DJ, Park SK. Low dose of mycophenolate mofetil is enough in desensitized kidney transplantation using rituximab. BMC Nephrol 2015; 16:201. [PMID: 26637210 PMCID: PMC4670498 DOI: 10.1186/s12882-015-0201-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2015] [Accepted: 11/30/2015] [Indexed: 12/12/2022] Open
Abstract
Background Rituximab is widely used in kidney transplantation. However, it is not clear whether the conventional doses of maintenance immunosuppressant in rituximab-treated kidney transplantation (KT) are appropriate. In our previous study, decreasing mycophenolate mofetil (MMF) dose due to infection did not increase the incidence of rejection or graft failure. Based on these experiences, we developed a new protocol with a lower dose of MMF and studied its clinical outcomes in rituximab-treated KT. Methods We enrolled all patients who underwent ABO-incompatible or human leukocyte antigen (HLA)-sensitized living donor KT with the new immunosuppressant protocol after preconditioning with rituximab, but without splenectomy from November 2011 to May 2013. Seventy-two patients (group 1) were consecutively enrolled in this study and followed until November 2013. Patients from our previous study served as control groups. Sixty-seven patients received KT using rituximab with a conventional dose of MMF (group 2), and 87 patients received ABO compatible KT without need for rituximab (group 3). Clinical outcomes, including rejection, infection, and graft survival, were compared between the groups. The χ2 test and Fisher’s exact test were used for categorical variables, the Student’s t-test and Mann-Whitney U test were used for continuous variables, and a log-rank test was used for mortality analysis. Results Doses of postoperative MMF (g/day) were lower in group 1 than in the other groups (1.03 ± 0.19, 1.48 ± 0.34 and 1.48 ± 0.32 g/day at 1 week, p < 0.001). Infectious complications occurred more often in groups with conventional MMF doses (group 2 and 3) than in group 1 (16.7 vs. 37.3 %, p = 0.007 and 16.7 vs. 34.5 %, p = 0.012, respectively). Notably, group 1 showed a lower incidence of cytomegalovirus infection than group 2. However, reduction in MMF dose did not increase the incidence of acute rejection (4.2, 4.5 and 10.3 %). Only one graft failure occurred in group 2 due to vessel kinking after operation. There were no significant differences in the incidence of malignancy and mortality between groups. Conclusions A low MMF dose reduces infection without increasing rejection or graft loss and it may be appropriate to reduce the dose of MMF for rituximab-treated KT patients.
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Affiliation(s)
- Chung Hee Baek
- Division of Nephrology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
| | - Hyosang Kim
- Division of Nephrology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
| | - Hoon Yu
- Division of Nephrology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
| | - Eunhye Shin
- Division of Nephrology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
| | - Hyungjin Cho
- Division of Nephrology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
| | - Won Seok Yang
- Division of Nephrology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
| | - Duck Jong Han
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
| | - Su-Kil Park
- Division of Nephrology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
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10
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Abstract
Kidney transplantation across the ABO blood group barrier was long considered a contraindication for transplantation, but in an effort to increase donor pools, specific regimens for ABO-incompatible (ABOi) transplantation have been developed. These regimens are now widely used as an integral part of the available treatment options. Various desensitization protocols, commonly based on transient depletion of preformed anti-A and/or anti-B antibodies and modulation of B-cell immunity, enable excellent transplant outcomes, even in the long-term. Nevertheless, the molecular mechanisms behind transplant acceptance facilitated by a short course of anti-humoral treatment are still incompletely understood. With the evolution of efficient clinical programmes, tailoring of recipient preconditioning based on individual donor-recipient blood type combinations and the levels of pretransplant anti-A/B antibodies has become possible. In the context of low antibody titres and/or donor A2 phenotype, immunomodulation and/or apheresis might be dispensable. A concern still exists, however, that ABOi kidney transplantation is associated with an increased risk of surgical and infectious complications, partly owing to the effects of extracorporeal treatment and intensified immunosuppression. Nevertheless, a continuous improvement in desensitization strategies, with the aim of minimizing the immunosuppressive burden, might pave the way to clinical outcomes that are comparable to those achieved in ABO-compatible transplantation.
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11
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Koo TY, Yang J. Current progress in ABO-incompatible kidney transplantation. Kidney Res Clin Pract 2015; 34:170-9. [PMID: 26484043 PMCID: PMC4608875 DOI: 10.1016/j.krcp.2015.08.005] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2015] [Revised: 08/12/2015] [Accepted: 08/12/2015] [Indexed: 02/07/2023] Open
Abstract
ABO-incompatible kidney transplantation (ABOi KT) was introduced to expand the donor pool and minimize shortage of kidneys for transplantation. Because improved outcomes of ABOi KT were reported in Japan in the early 2000s, the number of ABOi KTs has been increasing worldwide. In addition, a better understanding of immune pathogenesis and subsequent aggressive immunosuppression has helped to make effective desensitization protocols. Current strategies of ABOi KT consist of pretransplant antibody removal using plasmapheresis or immunoadsorption to prevent hyperacute rejection and potent maintenance immunosuppression, such as tacrolimus and mycophenolate mofetil, to inhibit antibody-mediated rejection. Recent outcomes of ABOi KT are comparable with ABO-compatible KT. However, there are still many problems to be resolved. Very high anti-ABO antibody producers are difficult to desensitize. In addition, ABOi KT is associated with an increased risk of infection and possibly malignancy due to aggressive immunosuppression. Optimization of desensitization and patient-tailored immunosuppression protocols are needed to achieve better outcomes of ABOi KT. This review provides an overview of the history, immune mechanism, immunosuppressive protocol, outcomes, current obstacles, and future perspectives in ABOi KT.
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Affiliation(s)
- Tai Yeon Koo
- Transplantation Center, Seoul National University Hospital, Transplantation Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jaeseok Yang
- Transplantation Center, Seoul National University Hospital, Transplantation Research Institute, Seoul National University College of Medicine, Seoul, Korea
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12
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Kassakian CT, Ajmal S, Gohh RY, Morrissey PE, Bayliss GP. Immunosuppression in the failing and failed transplant kidney: optimizing outcomes: Table 1. Nephrol Dial Transplant 2015; 31:1261-9. [DOI: 10.1093/ndt/gfv256] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2015] [Accepted: 05/19/2015] [Indexed: 11/14/2022] Open
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13
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Kim Y, Chung BH, Yang CW. Current Issues in ABO-Incompatible Kidney Transplantation. KOREAN JOURNAL OF TRANSPLANTATION 2014. [DOI: 10.4285/jkstn.2014.28.1.5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Affiliation(s)
- Yaeni Kim
- Department of Internal Medicine, The Catholic University of Korea, College of Medicine, Seoul, Korea
| | - Byung Ha Chung
- Department of Internal Medicine, The Catholic University of Korea, College of Medicine, Seoul, Korea
| | - Chul Woo Yang
- Department of Internal Medicine, The Catholic University of Korea, College of Medicine, Seoul, Korea
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Muramatsu M, Gonzalez HD, Cacciola R, Aikawa A, Yaqoob MM, Puliatti C. ABO incompatible renal transplants: Good or bad? World J Transplant 2014; 4:18-29. [PMID: 24669364 PMCID: PMC3964193 DOI: 10.5500/wjt.v4.i1.18] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2013] [Revised: 01/21/2014] [Accepted: 02/19/2014] [Indexed: 02/05/2023] Open
Abstract
ABO incompatible kidney transplantation (ABOi-KT) was previously considered to be an absolute contraindication for patients with end-stage kidney disease (ESKD) due to hyperacute rejection related to blood type barrier. Since the first successful series of ABOi-KT was reported, ABOi-KT is performed increasingly all over the world. ABOi-KT has led to an expanded donor pool and reduced the number of patients with ESKD awaiting deceased kidney transplantation (KT). Intensified immunosuppression and immunological understanding has helped to shape current desensitization protocols. Consequently, in recent years, ABOi-KT outcome is comparable to ABO compatible KT (ABOc-KT). However, many questions still remain unanswered. In ABOi-KT, there is an additional residual immunological risk that may lead to allograft damage, despite using current diverse but usually intensified immunosuppressive protocols at the expense of increasing risk of infection and possibly malignancy. Notably, in ABOi-KT, desensitization and antibody reduction therapies have increased the cost of KT. Reassuringly, there has been an evolution in ABOi-KT leading to a simplification of protocols over the last decade. This review provides an overview of the history, outcome, protocol, advantages and disadvantages in ABOi-KT, and focuses on whether ABOi-KT should be recommended as a therapeutic option of KT in the future.
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Nishioka S, Sofue T, Inui M, Nishijima Y, Moriwaki K, Hara T, Mashiba T, Kakehi Y, Kohno M. Mineral and Bone Disorder Is Temporary in Patients Treated With Early Rapid Corticosteroid Reduction After Kidney Transplantation: A Single-Center Experience. Transplant Proc 2014; 46:514-20. [DOI: 10.1016/j.transproceed.2013.11.153] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2013] [Revised: 10/25/2013] [Accepted: 11/27/2013] [Indexed: 12/12/2022]
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The First Fifty ABO Blood Group Incompatible Kidney Transplantations: The Rotterdam Experience. J Transplant 2014; 2014:913902. [PMID: 24672705 PMCID: PMC3941298 DOI: 10.1155/2014/913902] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2013] [Revised: 12/20/2013] [Accepted: 12/21/2013] [Indexed: 12/21/2022] Open
Abstract
This study describes the single center experience and long-term results of ABOi kidney transplantation using a pretransplantation protocol involving immunoadsorption combined with rituximab, intravenous immunoglobulins, and triple immune suppression. Fifty patients received an ABOi kidney transplant in the period from 2006 to 2012 with a follow-up of at least one year. Eleven antibody mediated rejections were noted of which 5 were mixed antibody and cellular mediated rejections. Nine cellular mediated rejections were recorded. Two grafts were lost due to rejection in the first year. One-year graft survival of the ABOi grafts was comparable to 100 matched ABO compatible renal grafts, 96% versus 99%. At 5-year follow-up, the graft survival was 90% in the ABOi versus 97% in the control group. Posttransplantation immunoadsorption was not an essential part of the protocol and no association was found between antibody titers and subsequent graft rejection. Steroids could be withdrawn safely 3 months after transplantation. Adverse events specifically related to the ABOi protocol were not observed. The currently used ABOi protocol shows good short and midterm results despite a high rate of antibody mediated rejections in the first years after the start of the program.
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The European Renal Best Practice (ERBP) Transplantation guideline development group, Abramowicz D, Cochat P, Claas F, Dudley C, Harden P, Heeman U, Hourmant M, Maggiore U, Pascual J, Salvadori M, Spasovski G, Squifflet JP, Steiger J, Torres A, Vanholder R, Van Biesen W, Viklicky O, Zeier M, Nagler E. ERBP Guideline on the Management and Evaluation of the Kidney Donor and Recipient. Nephrol Dial Transplant 2013; 28 Suppl 2:ii1-ii71. [PMID: 24026881 DOI: 10.1093/ndt/gft218] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
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Abstract
PURPOSE OF REVIEW A dramatic shortage of available organs around the world encouraged attempts to cross previously forbidden immunological boundaries in kidney transplantation. This review focuses on the recent results of ABO-incompatible kidney transplantation. RECENT FINDINGS The outcome of ABO-incompatible kidney transplantation in terms of patient and graft survival is comparable to ABO-compatible transplantation for adult and pediatric recipients. Splenectomy has been replaced by the B-cell-depleting agent rituximab to avoid isoagglutinin titer rebound, prevent antibody-mediated rejection, and improve graft survival. However, the risk for infections may be increased and warrants caution. Corticosteroids remain a necessary component of any ABO-incompatible protocol; early as well as late steroid withdrawal may bear an enhanced risk for acute rejection and should only be performed with careful follow-up including protocol biopsies. The few studies that have long-term outcomes using protocol biopsies have characterized a state of accommodation by up-regulation of complement inhibitors, down-regulation of A/B antigens, and establishment of endothelial chimerism over time. SUMMARY The experience accumulated around the world indicates that ABO-incompatible kidney transplantation is well tolerated and effective in adults and in children, and it represents an important step forward in expanding the living donor pool. Further understanding of ABO-incompatible graft accommodation may have broader implication also for human leukocyte antigen-sensitized allograft recipients.
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Sharif A, Alachkar N, Kraus E. Incompatible kidney transplantation: a brief overview of the past, present and future. QJM 2012; 105:1141-50. [PMID: 22908321 DOI: 10.1093/qjmed/hcs154] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Abstract
Live kidney donor transplantation across immunological barriers, either blood group or positive crossmatch [ABO- and human leucocyte antigens (HLA)-incompatible kidney transplantation, respectively], is now practised widely across many transplant centres. This provides transplantation opportunities to patients that hitherto would have been deemed contra-indicated and would subsequently have waited indefinitely for a suitably matched kidney. Protocols have evolved with time as experience has grown and now a variety of desensitization strategies are currently practised to overcome such immunological barriers. In addition, desensitization protocols are complemented by kidney paired donation exchange schemes and therefore incompatible patients now have strategies to either confront or bypass immunological barriers, respectively. As the field expands it is clear that non-transplant clinicians will be exposed to incompatible kidney transplant recipients outside of experienced centres. It is therefore timely to review the evolution of practice that have led to current desensitization modalities, contrast protocols and outcomes of current regimens and speculate on future direction of incompatible kidney transplantation.
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Affiliation(s)
- A Sharif
- Renal Institute of Birmingham, Queen Elizabeth Hospital, Edgbaston, Mindelsohn Way, Birmingham, B15 2WB, UK.
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Teschner S, Stippel D, Grunenberg R, Beck B, Wahba R, Gathof B, Benzing T, Burst V. ABO-incompatible kidney transplantation using regenerative selective immunoglobulin adsorption. J Clin Apher 2012; 27:51-60. [PMID: 22271603 DOI: 10.1002/jca.21201] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2011] [Accepted: 11/29/2011] [Indexed: 12/21/2022]
Abstract
BACKGROUND ABO-incompatible (ABOi) kidney transplantation is an established procedure relying on the removal of donor-specific isoagglutinine antibodies as part of the recipient preconditioning. At present, current protocols using immunoadsorption apply a single-use selective carbohydrate isoagglutinine adsorber. A regenerative and selective immunoglobulin immunoadsorption could be an alternative but has not been reported for ABOi transplantation. METHODS Eight patients were treated with the commonly used isoagglutinine carbohydrate epitope adsorber and seven with a regenerative polyclonal sheep anti-immunoglobulin adsorber as part of the preconditioning for ABOi kidney transplantation. An IgG-isoagglutinine titer of less or equal 1:4 qualified for transplantation. Treatment safety, efficiency, length of desensitization, number of postoperative immunoadsorptions, and allograft outcome were retrospectively compared. RESULTS With the use of the immunoglobulin adsorber the median initial isoagglutinine IgG titers of 1:64 (range 1:32-1:256) were lowered to the target of 1:4 preoperatively with a mean of 6.2 immunoadsorptions (range 5-11). Mean IgG/IgM titer step reduction per IA was 1.98/1.21 for (range 0-4/0-4) and mean titer step rebound 1.31/0.82 (range 0-4/0-3), respectively. The number of immunoadsorptions and length of desensitization was not different from the use of the specific isoagglutinine adsorbers. After transplantation, no rejection occurred and only one postoperative immunoadsorption was necessary. No adverse events in relation to immunoadsorption were observed. Graft function was comparable to the isoagglutinine adsorber group. CONCLUSION These data suggest that ABOi kidney transplantation can be performed safely and effectively with a selective regenerative immunoglobulin immunoadsorber.
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Affiliation(s)
- Sven Teschner
- Transplant Center Cologne, University Hospital Cologne, Cologne, Germany.
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Abstract
Any evaluation of steroids in kidney transplantation is hampered by individual variability in metabolism, the lack of clinically available steroid blood levels, and overall little attention to steroid exposure. Many feel that steroids were an essential part of chronic immunosuppression in past decades but may no longer be necessary in low-risk populations when our newer and more potent drugs are used. Potential differences in long-term outcome will be unapparent in short-term antibody induction studies in low-risk patients, particularly with low on steroid doses, as may have happened in the recent, well-done Astellas trial. In many studies, the evidence for the superiority of mycophenolate (MMF) and tacrolimus (TAC) was not as strong as the evidence for the benefit of steroids in the Canadian cyclosporine study. As the practice of steroid withdrawal has increased, we have not seen the improvement in long-term graft survival that many expected with our newer agents. Steroids have immunosuppressive effects even in doses that are low by historic standards, and side effects may not justify their abandonment.
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ABO-incompatible kidney transplantation: current practice and the decade ahead. Curr Opin Organ Transplant 2010; 15:526-30. [PMID: 20613520 DOI: 10.1097/mot.0b013e32833bfbba] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
PURPOSE OF REVIEW With rapidly growing deceased donor kidney transplant waiting lists, solutions to the shortage of kidney donors need to come from many corners. This review focuses on the current results and upcoming medications that will allow broad expansion of ABO-incompatible transplantation as one facet to combat this issue. RECENT FINDINGS Outcomes of ABO-incompatible kidney transplantation are comparable to standard living donor transplantation but carry a significant, early risk of antibody-mediated rejection. Reducing this early rejection risk will be critical for a broader adaption of incompatible transplants. Improvements in the measurement of isohemagglutinin antibodies with less variability, will reduce patient risk. The anti-CD20 antibody rituximab has replaced splenectomy at most centers with equivalent outcomes, eliminating the need for additional surgical intervention. Studies of complement inhibitors have proven effective in treating antibody-mediated rejection in animal models and human studies are currently ongoing. Studies in xenotransplantation show that blood group carbohydrate antigens can be effectively removed ex vivo prior to implantation. Ongoing studies of accommodation in animal models are finding protective changes in endothelial cells and the immune system that could become targets for pharmacologic manipulation. SUMMARY Improvements that reduce risk of early rejection and its long-term sequelae will allow ABO-incompatible kidney transplantation to be adopted broadly along with paired kidney exchange programs, to address the donor organ shortage.
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