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Takehara T, Nishida H, Ichikawa K, Nawano T, Takai S, Fukuhara H, Matsuura T, Maita S, Saito M, Murakami R, Hatakeyama S, Obara W, Saitoh H, Ohyama C, Habuchi T, Watanabe M, Tsuchiya N. Efficacy of valganciclovir prophylaxis in kidney transplant recipients following low-dose rituximab induction therapy: a multicenter retrospective study. Clin Exp Nephrol 2025; 29:359-367. [PMID: 39453573 DOI: 10.1007/s10157-024-02578-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Accepted: 10/12/2024] [Indexed: 10/26/2024]
Abstract
BACKGROUND Rituximab (RIT) induction therapy is widely used for desensitization against ABO-incompatible living-donor kidney transplants (KT). However, the efficacy of valganciclovir (VGCV) prophylaxis against cytomegalovirus (CMV) disease and infection in KT recipients (KTRs) following RIT induction remains unclear. METHODS The current multicenter retrospective study included 213 KTRs who received low-dose RIT induction between 1998 and 2021, across 6 facilities included in the Michinoku Renal Transplant Network (MRTN). VGCV dosage varied from 450 mg/day (twice weekly) to 900 mg/day (daily), with treatment durations of 3-12 months. The primary and secondary endpoints were the incidence of CMV disease and infection, respectively. RESULTS The incidence of CMV disease was significantly higher in the VGCV group (23.5%; 16 patients) than in the non-VGCV group (5.5%; 8 patients) (p < 0.01). The incidence of CMV infection was 54.5% (79 patients) in the non-VGCV group and 48.5% (33 patients) in the VGCV group, with no significant difference (p = 0.42). In the subgroup of CMV-seronegative KTRs receiving allografts from CMV-seropositive donors (CMV IgG (D + /R-)), 18 out of 24 KTRs received VGCV prophylaxis, of whom 10 (55.6%) developed CMV disease. Within this subgroup, only 4 KTRs received VGCV with the standard protocol (900 mg daily for 6 months), and none developed CMV disease. CONCLUSION Insufficient VGCV prophylaxis does not reduce the incidence of CMV disease in KTRs following low-dose RIT induction. Despite concerns about leukopenia due to RIT and VGCV, in KTRs with CMV IgG (D + /R-) serostatus, VGCV prophylaxis with a standard protocol may be advisable.
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Affiliation(s)
- Tomohiro Takehara
- Department of Cardiology, Pulmonology, and Nephrology, Faculty of Medicine, Yamagata University, Yamagata, Japan
| | - Hayato Nishida
- Department of Urology, Faculty of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
| | - Kazunobu Ichikawa
- Department of Cardiology, Pulmonology, and Nephrology, Faculty of Medicine, Yamagata University, Yamagata, Japan
| | - Takaaki Nawano
- Department of Cardiology, Pulmonology, and Nephrology, Faculty of Medicine, Yamagata University, Yamagata, Japan
| | - Satoshi Takai
- Department of Urology, Faculty of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan
| | - Hiroki Fukuhara
- Department of Urology, Faculty of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan
| | - Tomohiko Matsuura
- Department of Urology, Iwate Medical University, Morioka, Iwate, Japan
| | - Shinya Maita
- Department of Urology, Iwate Prefectural Isawa Hospital, Oshu, Iwate, Japan
| | - Mitsuru Saito
- Department of Urology, Akita University School of Medicine, Akita, Japan
| | - Reiichi Murakami
- Department of Cardiology and Nephrology, Hirosaki University School of Medicine, Hirosaki, Aomori, Japan
| | - Shingo Hatakeyama
- Department of Urology, Hirosaki University School of Medicine, Hirosaki, Aomori, Japan
| | - Wataru Obara
- Department of Urology, Iwate Medical University, Morioka, Iwate, Japan
| | - Hisao Saitoh
- Department of Urology, Oyokyo Kidney Research Institute, Hirosaki, Aomori, Japan
| | - Chikara Ohyama
- Department of Urology, Hirosaki University School of Medicine, Hirosaki, Aomori, Japan
| | - Tomonori Habuchi
- Department of Urology, Akita University School of Medicine, Akita, Japan
| | - Masafumi Watanabe
- Department of Cardiology, Pulmonology, and Nephrology, Faculty of Medicine, Yamagata University, Yamagata, Japan
| | - Norihiko Tsuchiya
- Department of Urology, Faculty of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan
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Naciri Bennani H, Bobo Barry KM, Noble J, Malvezzi P, Jouve T, Rostaing L. Outcomes of ABO-incompatible kidney transplants with very high isoagglutinin titers: a single-center experience and literature review. Front Immunol 2024; 15:1504495. [PMID: 39687613 PMCID: PMC11647008 DOI: 10.3389/fimmu.2024.1504495] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Accepted: 11/13/2024] [Indexed: 12/18/2024] Open
Abstract
Background ABO-incompatible kidney transplantation (ABOi-KTx) represents a possible solution to address the shortage of kidney donors. However, these transplants present immunological challenges, particularly when isoagglutinin titers are elevated pretransplant. Methods Single-center retrospective study describing clinical and biological outcomes of 8 patients who underwent ABOi-KTx with initial isoagglutinin titers ≥ 1/512. All patients followed a desensitization protocol combining immunosuppression (rituximab, tacrolimus, mycophenolate mofetil, steroids), and specific or semi-specific apheresis sessions. Clinical and biological data were extracted from electronic medical records. Results There were 5 males; median age of 62 years [34-82 years]; all achieved an isoagglutinin titer of ≤1/8 before transplantation after a median of 13 (range: 9-15) apheresis sessions. Three patients (37%) experienced acute humoral rejection, which required additional plasmapheresis sessions. Two patients developed chronic active rejection, successfully treated. On the infectious side, three patients developed BK-virus reactivation. Two patients developed cytomegalovirus viremia, and two others presented with bacterial infections. Surgically, two patients developed a lymphocele, and one had a perirenal hematoma. All patients survived the transplant with stable renal function: mean serum creatinine was 138 ± 15 µmol/L after four years of follow-up. Conclusion ABO-incompatible kidney transplantation, even in patients with high isoagglutinin titers, is feasible and can achieve favorable long-term graft and patient survival outcomes. However, these procedures require substantial clinical expertise and close follow-up to monitor and manage the elevated risks of infection and rejection in this population.
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Affiliation(s)
- Hamza Naciri Bennani
- Nephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, Grenoble University Hospital, Grenoble, France
| | - Kadiatou Mamadou Bobo Barry
- Nephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, Grenoble University Hospital, Grenoble, France
| | - Johan Noble
- Nephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, Grenoble University Hospital, Grenoble, France
| | - Paolo Malvezzi
- Nephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, Grenoble University Hospital, Grenoble, France
| | - Thomas Jouve
- Nephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, Grenoble University Hospital, Grenoble, France
- Grenoble-Alpes University, Grenoble, France
| | - Lionel Rostaing
- Nephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, Grenoble University Hospital, Grenoble, France
- Grenoble-Alpes University, Grenoble, France
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Kim JM, Kwon HE, Ko Y, Jung JH, Kwon H, Kim YH, Shin S. A comparative study on outcomes of ABO-incompatible kidney transplants between robot-assisted vs. open surgery-propensity score-matched analysis: a retrospective cohort study. BMC Nephrol 2024; 25:410. [PMID: 39543527 PMCID: PMC11566057 DOI: 10.1186/s12882-024-03842-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Accepted: 10/30/2024] [Indexed: 11/17/2024] Open
Abstract
BACKGROUND Robot-assisted kidney transplantation (RAKT) is increasingly being adopted worldwide. Despite this growing interest, there remains a notable gap in the literature, especially concerning its effectiveness in immunologically high-risk patients compared to conventional open kidney transplantation (OKT). This study investigates the viability and success of RAKT in comparison with OKT, particularly for recipients with ABO incompatibility (ABOi). METHODS This retrospective, single-center study included 239 living-donor transplants between October 2020 and February 2023, with 210 patients undergoing ABOi-OKT and 29 undergoing ABOi-RAKT. A composite of biopsy-proven acute rejection (BPAR), graft failure, and the development of de novo donor-specific antibodies was analyzed through univariate and multivariate models. Propensity score matching (PSM) was utilized to ensure a balanced comparison between the two groups. Following PSM, a total of 131 cases in the OKT group and 26 cases in the RAKT group were analyzed. RESULTS After PSM, the mean recipient age was 48.56 years for OKT and 47.96 years for RAKT. Both groups had comparable one-year (RAKT: 92.4%, OKT: 93.1%) and two-year BPAR-free survival rates (RAKT: 92.4%, OKT: 91.9%). Mean estimated glomerular filtration rate values were similar at 12 months post-transplant (RAKT: 62.15 ml/min/1.73 m², OKT: 64.53 ml/min/1.73 m²). Operative times were significantly longer for RAKT (291.42 vs. 150.81 min, p < 0.001), while cold ischemic time was also longer for RAKT (119.77 vs. 47.22 min, p < 0.001). Hospital stays were shorter for RAKT (median 6 vs. 8 days, p < 0.001). There was no significant difference in the composite outcome of BPAR, graft failure, and de novo donor-specific antibodies between the two groups (HR 0.858, 95% CI: 0.180-4.096, p = 0.848). CONCLUSIONS RAKT is a safe and effective alternative to OKT in ABOi patients, demonstrating similar perioperative outcomes, graft survival rates, and renal function. The application of ropensity score matching analysis strengthens the reliability of these findings, confirming RAKT's viability for high-risk kidney transplant recipients. TRIAL REGISTRATION The clinical trial associated with this study was registered on 2024-02-24 with the Clinical Trial Number NCT06287008|| https://www. CLINICALTRIALS gov/ ).
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Affiliation(s)
- Jin-Myung Kim
- Division of Kidney and Pancreas Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Hye Eun Kwon
- Division of Kidney and Pancreas Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Youngmin Ko
- Division of Kidney and Pancreas Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Joo Hee Jung
- Division of Kidney and Pancreas Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Hyunwook Kwon
- Division of Kidney and Pancreas Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Young Hoon Kim
- Division of Kidney and Pancreas Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Sung Shin
- Division of Kidney and Pancreas Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.
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Shekhrajka P, Mandal S, Goyal VK, Mittal S, Khunteta N, Mishra A. Perioperative outcomes of 105 cases of ABO-incompatible live donor kidney transplantation: a retrospective single-center observational study. CLINICAL TRANSPLANTATION AND RESEARCH 2024; 38:197-202. [PMID: 39251569 PMCID: PMC11464150 DOI: 10.4285/ctr.24.0028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Revised: 06/24/2024] [Accepted: 08/10/2024] [Indexed: 09/11/2024]
Abstract
Background ABO-incompatible (ABOi) kidney transplantation poses significant challenges in achieving successful outcomes. This study aimed to investigate the impact of various interventions and techniques on improving the success rates of ABOi kidney transplantation. Methods We conducted a retrospective observational analysis of patients who underwent ABOi kidney transplantation from November 2012 to March 2023. The study included a total of 105 patients. We collected and analyzed data on patient demographics, preoperative assessments, surgical details, and postoperative outcomes. Results The mean ages of the donors and recipients were 50.52±10.32 and 36.63±11.61 years, respectively. The majority of recipients were male (81.9%), while most donors were female (89.5%). The most common blood group among recipients was O (69.5%), and among donors, it was B (46.7%). The median durations of chronic kidney disease and dialysis were 12 months (interquartile range [IQR], 7-28 months) and 6 months (IQR, 2-12 months), respectively. Baseline antibody titers (anti-A and anti-B) ranged from 64.0 to 256.0, while on the day of surgery, they were ≤8. Perioperative complications included hypotension (10.5%), acute tubular necrosis (5.7%), delayed graft function (3.8%), and reexploration (3.8%) due to hematoma. Conclusions ABOi kidney transplantation is a viable option for recipients lacking available donors with an ABO-compatible match. Perioperative concerns, including hypoalbuminemia, heightened risk of infections, coagulopathies, aseptic precautions, and immunological surveillance, must be carefully addressed.
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Affiliation(s)
- Praveenkumar Shekhrajka
- Department of Anaesthesia and Critical Care, Mahatma Gandhi Medical College and Hospital, Jaipur, India
| | - Sony Mandal
- Department of Pathology, Mahatma Gandhi Medical College and Hospital, Jaipur, India
| | - Vipin Kumar Goyal
- Department of Organ Transplant Anaesthesia and Critical Care, Mahatma Gandhi Medical College and Hospital, Jaipur, India
| | - Saurabh Mittal
- Department of Organ Transplant Anaesthesia and Critical Care, Mahatma Gandhi Medical College and Hospital, Jaipur, India
| | - Nihit Khunteta
- Department of Anaesthesia and Critical Care, Mahatma Gandhi Medical College and Hospital, Jaipur, India
| | - Akash Mishra
- Division of Biostatistics, Department of Community Medicine, Mahatma Gandhi Medical College and Hospital, Jaipur, India
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Kodama H, Hatakeyama S, Matsuura T, Saito M, Nishida H, Hamaya T, Maita S, Murakami R, Tomita H, Saitoh H, Tsuchiya N, Habuchi T, Obara W, Ohyama C. Incidence of postoperative cytomegalovirus and BK-polyoma virus infections and graft loss in ABO-incompatible renal transplant recipients: a multicenter retrospective study. Int Urol Nephrol 2024; 56:2187-2193. [PMID: 38332424 DOI: 10.1007/s11255-023-03934-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Accepted: 12/27/2023] [Indexed: 02/10/2024]
Abstract
OBJECTIVES The current study aimed to examine the incidence of perioperative infections and graft viability in ABO-compatible and ABO-incompatible renal transplant recipients. METHODS We included 643 living donor renal transplant recipients registered in the Michinoku Renal Transplant Network from 1998 to 2021. Patients were divided into the ABO-compatible and ABO-incompatible kidney transplantation groups. We compared the characteristics of the two groups and evaluated the incidence of postoperative viral infections (cytomegalovirus and BK virus), graft loss-free survival, and overall survival between the two groups. RESULTS Of 643 patients, 485 (75%) and 158 (25%) were ABO-compatible and ABO-incompatible renal transplant recipients, respectively. Postoperative viral infections, rituximab use, and plasma exchange were significantly more common in ABO-incompatible than in ABO-compatible transplant recipients. However, there were no significant differences in terms of other background characteristics. The ABO-incompatible group was more likely to develop viral infections than the ABO-compatible group. Graft loss-free survival and overall survival did not significantly differ between the two groups. According to the multivariate Cox regression analysis, ABO compatibility was not significantly associated with graft loss-free survival and overall survival. CONCLUSION Although the incidence of postoperative viral infections in ABO-incompatible renal transplant recipients increased, there was no significant difference in terms of rejection events, graft loss-free survival, and overall survival.
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Affiliation(s)
- Hirotake Kodama
- Department of Urology, Hirosaki University School of Medicine, 5 Zaifu-Cho, Hirosaki, Aomori, 036-8562, Japan
| | - Shingo Hatakeyama
- Department of Advanced Blood Purification Therapy, Hirosaki University Graduate School of Medicine, 5 Zaifu-Cho, Hirosaki, Aomori, 036-8562, Japan.
| | - Tomohiko Matsuura
- Department of Urology, Iwate Medical University, 1-1-1 Idaidori, Yahaba-Cho, Shiwa-Gun, Morioka, Iwate, 028-3694, Japan
| | - Mitsuru Saito
- Department of Urology, Akita University School of Medicine, 1-1-1, Hondo, Akita, 010-8543, Japan
| | - Hayato Nishida
- Department of Urology, Faculty of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, 990-9585, Japan
| | - Tomoko Hamaya
- Department of Urology, Hirosaki University School of Medicine, 5 Zaifu-Cho, Hirosaki, Aomori, 036-8562, Japan
| | - Shinya Maita
- Department of Urology, Iwate Prefectural Isawa Hospital, 61 Mizusawaryuugababa, Oshu, Iwate, 023-0864, Japan
| | - Reiichi Murakami
- Department of Cardiology and Nephrology, Hirosaki University School of Medicine, 5 Zaifu-Cho, Hirosaki, Aomori, 036-8562, Japan
| | - Hirofumi Tomita
- Department of Cardiology and Nephrology, Hirosaki University School of Medicine, 5 Zaifu-Cho, Hirosaki, Aomori, 036-8562, Japan
| | - Hisao Saitoh
- Department of Urology, Oyokyo Kidney Research Institute, 90 Kozawayamazaki, Hirosaki, Aomori, 036-8243, Japan
| | - Norihiko Tsuchiya
- Department of Urology, Faculty of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, 990-9585, Japan
| | - Tomonori Habuchi
- Department of Urology, Akita University School of Medicine, 1-1-1, Hondo, Akita, 010-8543, Japan
| | - Wataru Obara
- Department of Urology, Iwate Medical University, 1-1-1 Idaidori, Yahaba-Cho, Shiwa-Gun, Morioka, Iwate, 028-3694, Japan
| | - Chikara Ohyama
- Department of Urology, Hirosaki University School of Medicine, 5 Zaifu-Cho, Hirosaki, Aomori, 036-8562, Japan
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Lee JH, Lee HR, Lee SW, Song JH, Hwang SD. Effect of Induction Therapy Dose on Survival in Abo-Incompatible Kidney Transplantation: A Network Meta-Analysis Using Recent Data. Transplant Proc 2024; 56:511-514. [PMID: 38378338 DOI: 10.1016/j.transproceed.2024.01.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2023] [Accepted: 01/16/2024] [Indexed: 02/22/2024]
Abstract
BACKGROUND Rituximab is an essential induction immunosuppressant for ABO-incompatible kidney transplantation (KT) (ABOi-KT). However, studies on the optimal dose of rituximab are insufficient, and there are dosage differences between transplant centers and countries. Therefore, we conducted a study to determine the survival outcomes of patients receiving the most effective and safe dose of rituximab during ABOi-KT. METHODS Studies on rituximab dose were divided into four groups: ABO compatible, 1) placebo, 2) rituximab 200 mg, 3) rituximab 200-500 mg, and 4) rituximab 500 mg. We searched the CENTRAL, MEDLINE, EMBASE, and Science Citation Index Expanded databases from 1970 to February 2022.9 . The inclusion criteria were adult patients (>18 years old). Reviews, observational studies, and clinical trials that did not clearly define outcomes or that did not have graft failure as an outcome were excluded. We performed direct and indirect network meta-analyses using Bayesian models and ranked different rituximab doses using a generation mixed treatment comparison (GeMTC) and Stata version 13. The NMA approach was evaluated using the GRADE framework, which specifies four levels of certainty for a given result: high, moderate, low, and very low. The outcomes included patient survival, graft failure, and bacterial and viral infections. RESULTS Twenty-five trials, including 5,378 subjects, were divided into the following four groups: 1) placebo, 2) rituximab 200 mg, 3) rituximab 200-500 mg, and 4) rituximab 500 mg. We focused on survival outcomes according to the dose of rituximab when patients received induction therapy for ABOi-KT. The mortality rate was significantly lower in the ABO-compatible and rituximab 200 mg groups (odds ratio [OR] 0.27, 95% CrI: 0.071-0.91 and OR 0.14, 95% CrI 0.036-0.47), compared with that in the placebo group. CONCLUSIONS We found that low-dose rituximab in ABO-i KT was effective compared to the high-dose and placebo in maintaining the survival rate. However, large-scale and long-term data are necessary for further validation of our findings. Additionally, the use of smaller doses of rituximab will require further discussion.
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Affiliation(s)
- Jin Ho Lee
- Division of Nephrology, Department of Internal Medicine, Leesin Hemodialysis and Intervention Clinic, Busan, Korea
| | - Hee Ryong Lee
- Division of Nephrology, Department of Internal Medicine, Leesin Hemodialysis and Intervention Clinic, Busan, Korea
| | - Seoung Woo Lee
- Division of Nephrology and Hypertension, Department of Internal Medicine, Inha University School of Medicine, Incheon, Korea
| | - Joon Ho Song
- Division of Nephrology and Hypertension, Department of Internal Medicine, Inha University School of Medicine, Incheon, Korea
| | - Seun Deuk Hwang
- Division of Nephrology and Hypertension, Department of Internal Medicine, Inha University School of Medicine, Incheon, Korea.
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El Chediak A, Shawar S, Fallahzadeh MK, Forbes R, Schaefer HM, Feurer ID, Rega S, Triozzi JL, Shaffer D. A2/A2B to B kidney transplantation outcomes: A single center 7-year experience. Clin Transplant 2024; 38:e15295. [PMID: 38545909 DOI: 10.1111/ctr.15295] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 02/20/2024] [Accepted: 03/08/2024] [Indexed: 04/20/2024]
Abstract
INTRODUCTION Data on long-term outcomes following A2/A2B to B kidney transplants since the 2014 kidney allocation system (KAS) changes are few. The primary aim of this study is to report our 7-year experience with A2/A2B to B kidney transplants and to compare post-transplant outcomes of A2/A2B to a concurrent group of B to B kidney transplants. Additionally, the study evaluates the impact of pre-transplant anti-A1 titers on survival outcomes in A2/A2B transplants. METHODS This retrospective, single-center analysis included all adults who received A2/A2B to B deceased donor kidney transplants from December 2014 to June 2021 compared to B to B recipients. The effects of pre-transplant IgM/IgG titers, stratified as ≤1:8 and ≥1:16, on death-censored, rejection-free, and overall graft survival were tested. RESULTS Fifty-three A2/A2B and 114 B to B adults were included with a median follow-up time of 32 months. Overall graft survival, patient survival, and rejection-free graft survival did not differ between the two groups. There were no differences between the groups' overall kidney function values (p > .80) or their temporal trajectories (time by group interaction p > .11). Unadjusted death-censored graft survival was lower in A2/A2B to B compared to B recipients (p = .03), but the effect was not significant (p = .195) after adjusting for any readmissions (p = .96), rejection episodes (p < .001) or BK infection (p = .76). We did not detect an effect of pre-transplant titer group on death-censored (p = .59), rejection-free (p = .61), or overall graft survival (p = .26) CONCLUSIONS: A2/A2B to B kidney transplants have comparable overall patient and graft survival, rejection-free graft survival, and longitudinal renal function compared to B to B transplants at our center. Allograft survival outcomes were not significantly different between patients with low and high pre-transplant anti-A1 IgM/IgG titers.
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Affiliation(s)
- Alissar El Chediak
- Department of Internal Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Saed Shawar
- Department of Medicine, Division of Kidney and Pancreas Transplant, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Mohammad K Fallahzadeh
- Division of Nephrology, Emory Transplant Center, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Rachel Forbes
- Department of Surgery, Division of Kidney and Pancreas Transplant, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Heidi M Schaefer
- Department of Medicine, Division of Kidney and Pancreas Transplant, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Irene D Feurer
- Department of Surgery, Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Scott Rega
- Vanderbilt Transplant Center, Nashville, Tennessee, USA
| | - Jefferson L Triozzi
- Department of Medicine, Division of Kidney and Pancreas Transplant, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - David Shaffer
- Department of Surgery, Division of Kidney and Pancreas Transplant, Vanderbilt University Medical Center, Nashville, Tennessee, USA
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Matuschik L, Seifert G, Lammich K, Holzner P, Tanriver Y, Fichtner-Feigl S, Walz G, Schneider J, Jänigen B. Non-antigen-specific Immunoadsorption Is a Risk Factor for Severe Postoperative Infections in ABO-Incompatible Kidney Transplant Recipients. Transpl Int 2024; 37:12263. [PMID: 38550626 PMCID: PMC10974667 DOI: 10.3389/ti.2024.12263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Accepted: 03/01/2024] [Indexed: 04/02/2024]
Abstract
ABO-incompatible (ABOi) living kidney transplantation (KTx) is an established procedure to address the demand for kidney transplants with outcomes comparable to ABO-compatible KTx. Desensitization involves the use of immunoadsorption (IA) to eliminate preformed antibodies against the allograft. This monocentric retrospective study compares single-use antigen-selective Glycosorb® ABO columns to reusable non-antigen-specific Immunosorba® immunoglobulin adsorption columns regarding postoperative infectious complications and outcome. It includes all 138 ABOi KTx performed at Freiburg Transplant Center from 2004-2020. We compare 81 patients desensitized using antigen-specific columns (sIA) to 57 patients who received IA using non-antigen-specific columns (nsIA). We describe distribution of infections, mortality and allograft survival in both groups and use Cox proportional hazards regression to test for the association of IA type with severe infections. Desensitization with nsIA tripled the risk of severe postoperative infections (adjusted HR 3.08, 95% CI: 1.3-8.1) compared to sIA. nsIA was associated with significantly more recurring (21.4% vs. 6.2%) and severe infections (28.6% vs. 8.6%), mostly in the form of urosepsis. A significantly higher proportion of patients with sIA suffered from allograft rejection (29.6% vs. 14.0%). However, allograft survival was comparable. nsIA is associated with a two-fold risk of developing a severe postoperative infection after ABOi KTx.
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Affiliation(s)
- Laura Matuschik
- Department of General and Visceral Surgery, Section of Transplant Surgery, Faculty of Medicine, Medical Center–University of Freiburg, Freiburg, Germany
| | - Gabriel Seifert
- Department of General and Visceral Surgery, Section of Transplant Surgery, Faculty of Medicine, Medical Center–University of Freiburg, Freiburg, Germany
| | - Katrin Lammich
- Department of General and Visceral Surgery, Section of Transplant Surgery, Faculty of Medicine, Medical Center–University of Freiburg, Freiburg, Germany
| | - Philipp Holzner
- Department of General and Visceral Surgery, Section of Transplant Surgery, Faculty of Medicine, Medical Center–University of Freiburg, Freiburg, Germany
| | - Yakup Tanriver
- Department of Medicine IV, Faculty of Medicine, Medical Center–University of Freiburg, Freiburg, Germany
| | - Stefan Fichtner-Feigl
- Department of General and Visceral Surgery, Section of Transplant Surgery, Faculty of Medicine, Medical Center–University of Freiburg, Freiburg, Germany
| | - Gerd Walz
- Department of Medicine IV, Faculty of Medicine, Medical Center–University of Freiburg, Freiburg, Germany
| | - Johanna Schneider
- Department of Medicine IV, Faculty of Medicine, Medical Center–University of Freiburg, Freiburg, Germany
| | - Bernd Jänigen
- Department of General and Visceral Surgery, Section of Transplant Surgery, Faculty of Medicine, Medical Center–University of Freiburg, Freiburg, Germany
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9
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Pandey P, Tiwari A, Shekhar Das S, Shastry S, Kute V, Chowdhry M, Marik A, Aggarwal G, Kumari S, Setya D, Mandal S, Ranjan S. I-JAMM-(I): A survey providing an insight into the practices of isoagglutinin titration in ABO incompatible kidney and liver transplantation. Transfus Apher Sci 2024; 63:103862. [PMID: 38135545 DOI: 10.1016/j.transci.2023.103862] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Revised: 11/22/2023] [Accepted: 12/01/2023] [Indexed: 12/24/2023]
Abstract
BACKGROUND AND OBJECTIVES ABO-incompatible transplantations allow patients to receive timely transplants. Isoagglutinin titration to ascertain levels of incompatible antibodies in the recipient is important in determining patient selection and transplant survivability. To find out the prevalent trends in India, the largest, first of its kind survey was carried out among the transplant centers regarding their practices in isoagglutinin titration. METHODS The survey was drafted by a working group of Transfusion and Transplant Immunology specialists from six different centers. Data was obtained via the use of an online questionnaire. RESULTS Results were categorized into four categories, Hospital information, Titration methodology, Role of transfusion specialists and cut-off titers. Most centers had a well-established solid-organ transplant program with considerable number of ABO-incompatible transplantations. Most centers performed isoagglutinin titration in Transfusion Medicine department. Column Agglutination Technique (CAT) was the most common method, using EDTA blood samples and freshly-prepared in-house pooled cells. Most centers had a turn-around time of less than 12 h. While the policy for ascertaining baseline and threshold titers is well-defined in ABO-incompatible renal transplants, variations from center to center still exist for ABO-incompatible liver transplants. Most centers required a Transfusion Medicine consultation for the patients before such transplants. CONCLUSION With increasing ABO-incompatible kidney and liver transplants across the country, the role of Transfusion medicine specialists has become vital in pre-conditioning regimes enabling the viability and success of such transplants. This was a unique survey that provided a snapshot of current trends and practices of isoagglutinin titration for ABO-incompatible transplants in India.
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Affiliation(s)
- Prashant Pandey
- Department of Transfusion Medicine & Transplant Immunology, Jaypee Hospital, Sector, 128, Noida 201304, India
| | - Aseem Tiwari
- Department of Transfusion Medicine, Medanta, The Medicity, Gurugram, India
| | | | - Shamee Shastry
- Department of Immunohematology and Blood Transfusion, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India 576104
| | - Vivek Kute
- Department of Nephrology, Institute of Kidney Diseases and Research Center, Ahmedabad, India
| | - Mohit Chowdhry
- Department of Transfusion Medicine, Indaprastha Apollo Hospital, New Delhi, India
| | - Arghyadeep Marik
- Department of Transfusion Medicine & Transplant Immunology, Jaypee Hospital, Sector, 128, Noida 201304, India.
| | - Geet Aggarwal
- Department of Transfusion Medicine, Medanta, The Medicity, Gurugram, India
| | - Supriya Kumari
- Department of Transfusion Medicine & Transplant Immunology, Jaypee Hospital, Sector, 128, Noida 201304, India
| | - Divya Setya
- Department of Transfusion Medicine, Manipal Hospital, Jaipur, India
| | - Saikat Mandal
- Department of Transfusion Medicine & Transplant Immunology, Jaypee Hospital, Sector, 128, Noida 201304, India
| | - Shweta Ranjan
- Department of Transfusion Medicine, All India Institute of Medical Sciences, Patna, India
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10
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Xu P, Zhao N, Wang J. Success rate and safety of living donor kidney transplantation in ABO blood group incompatible relatives: A systematic review and meta-analysis. Transpl Immunol 2023; 81:101921. [PMID: 37648033 DOI: 10.1016/j.trim.2023.101921] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 08/15/2023] [Accepted: 08/27/2023] [Indexed: 09/01/2023]
Abstract
BACKGROUND Kidney transplantation is considered an ideal treatment for end-stage renal disease (ESRD) because it provides a longer and better quality of life than dialysis. ABO-incompatible (ABO-I) kidney transplantation relies on two principles: (i) removal of antibodies from a blood group; and (ii) inhibition of reappearance of blood group antibodies by intensifying the induction and maintenance of immunosuppression. This systematic review aimed to analyze the success and safety of ABO-I live-donor kidney transplantation. METHODS Databases, including Google Scholar, PubMed, Embase, Web of Science, and Medline were searched. Search duration was from the database establishment to December 2022. A thorough search was performed for relevant studies investigating the success and safety of ABO-I live-donor kidney transplantation. Two investigators independently extracted literature information and assessed the quality of the included studies. Heterogeneity test was performed using Cochrane's Q and chi-squared tests. All statistical analyses were performed using R software (version 4.2.1). RESULTS The search for relevant literature in the five electronic databases yielded 1238 articles. Of the 1238 articles, only 15 were included. Meta-analysis of outcomes from five studies showed a survival rate of 0.93 (95% confidence interval [CI]: 0.88 to 0.97, P < 0.001) after ≥3 years, while outcomes from 12 studies revealed a short-term patient survival rate of 0.94 (95% CI: 0.92 to 0.96, P = 0.75). In contrast, long- and short-term graft survival rates were 0.89 (95% CI: 0.75 to 0.96, P < 0.001) and 0.94 (95% CI: 0.90 to 0.97, P < 0.001), respectively. Incidence rates of infectious, surgical, and medical complications were 0.31 (95% CI: 0.22 to 0.41, P < 0.001), 0.12 (95% CI: 0.05 to 0.25, P < 0.001), and 0.38 (95% CI: 0.17 to 0.66, P < 0.001), respectively. CONCLUSION Good long- and short-term patient outcomes and graft survival rates were observed after ABO-I kidney transplantation. Similarly, the safety of performing kidney transplantations from living donors with ABO-I blood groups was established by the results of the current meta-analysis. Therefore, ABO-I live-donor kidney transplantations should be encouraged to reduce the time recipients spend on waiting lists and supplement the existing paired-exchange donor program.
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Affiliation(s)
- Pengjie Xu
- Department of Nephrology, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang 315000, China.
| | - Nadan Zhao
- Department of Radiology, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang 315000, China
| | - Jiangdong Wang
- Department of Nephrology, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang 315000, China
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11
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John GT, Jacob CK, Sundaram M, Alexander S, Kekre NS, Daniel D, Varughese S. The First ABO Incompatible Kidney Transplantation without Splenectomy in India - A Review at 12 Years. Indian J Nephrol 2023; 33:234-236. [PMID: 37448893 PMCID: PMC10337219 DOI: 10.4103/ijn.ijn_295_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 08/31/2021] [Accepted: 11/14/2021] [Indexed: 07/15/2023] Open
Affiliation(s)
- George T. John
- Kidney Health Service, Royal Brisbane and Women’s Hospital, Brisbane, Herston, Queensland, Australia, India
| | - Chakko K. Jacob
- Department of Nephrology, Bangalore Baptist Hospital, Bengaluru, Karnataka, India
| | - Madhivanan Sundaram
- Department of Nephrology, Royal Darwin Hospital, Darwin, Northern Territory, Australia
| | - Suceena Alexander
- Department of Nephrology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Nitin S. Kekre
- Department of Urology, Naruvi Hospitals, Vellore, Tamil Nadu, India
| | - Dolly Daniel
- Department of Transfusion Medicine and Immunohaematology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Santosh Varughese
- Department of Nephrology, Christian Medical College, Vellore, Tamil Nadu, India
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12
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Guy P, Delas A, Esposito L, Cointault O, Colombat M, Congy-Jolivet N, Raynaud M, Kamar N, Del Bello A. Progression of histological lesions after ABO incompatible kidney transplantation. Front Immunol 2022; 13:969998. [PMID: 36275771 PMCID: PMC9582152 DOI: 10.3389/fimmu.2022.969998] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Accepted: 09/06/2022] [Indexed: 11/22/2022] Open
Abstract
Recent large meta-analyses suggested a poorer long-term patients’ and grafts’ outcomes after ABO incompatible (ABOi) living-donor kidney transplantation (LDKT) compared to ABO compatible LDKT. However, little is known about the long-term histological pattern after ABOi LDKT. We compared the histological features observed on protocol biopsies from 03/11 to 11/19 in 94 ABOi LDKT (including 14 with preformed Donor Specific Antibodies, pDSAs), 27 LDKT ABO compatible (ABOc) with pDSAs, and 21 ABOc without pDSAs) during the first five years post transplantation. During the first 5 years post-transplantation, a progression of chronic lesions (patients with a ci >0 raised from 11% to 65%, p<0.0001, patients with a ct >0 raised from 29% to 78%, p<0.0001) was observed in ABOi LDKT without pDSAs. Histological patterns of evolution were comparable to those observed in ABOc kidney transplant patients. Microvascular inflammation was lower in ABOi LDKT without pDSAs compared to those with pDSAs (ABOi or ABOc). At last follow-up, 28 months, IQR (15-48) post-transplantation, 29 patients (36%) had a severe graft dysfunction (defined by a CKD-epi eGFR < 30 mL/min/1.73m²). The donor age was a predictive factor for the development of severe kidney allograft dysfunction at last follow-up (HR= 1.05, 95% CI [1.05-1.10], p= 0.03). Hence, long-term histological analysis of ABOi LDKT shows only an increase of chronic interstitial and tubular atrophy changes, without active lesions. These data confirm that ABOi LDKT programs can be securely developed.
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Affiliation(s)
- Pierre Guy
- Department of Nephrology and Organ Transplantation, Centre Hospitalier et Universitaire (CHU), Toulouse, France
| | - Audrey Delas
- Department of Pathology, Toulouse University Hospital, Toulouse, France
| | - Laure Esposito
- Department of Nephrology and Organ Transplantation, Centre Hospitalier et Universitaire (CHU), Toulouse, France
| | - Olivier Cointault
- Department of Nephrology and Organ Transplantation, Centre Hospitalier et Universitaire (CHU), Toulouse, France
| | - Magali Colombat
- Department of Pathology, Toulouse University Hospital, Toulouse, France
- Centre Hospitalier et Universitaire, Université Paul Sabatier Toulouse III, Toulouse, France
| | - Nicolas Congy-Jolivet
- Laboratory of Immunology, Biology Department, Centre Hospitalier et Universitaire (CHU) de Toulouse, Toulouse, France
| | - Marc Raynaud
- Paris Translational Research Epidemiology and Biostatistics Department, Université de Paris, INSERM U970, PARCC, Paris, France
| | - Nassim Kamar
- Department of Nephrology and Organ Transplantation, Centre Hospitalier et Universitaire (CHU), Toulouse, France
- Centre Hospitalier et Universitaire, Université Paul Sabatier Toulouse III, Toulouse, France
- Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), INSERM UMR1043-CNRS 5282, Toulouse, France
| | - Arnaud Del Bello
- Department of Nephrology and Organ Transplantation, Centre Hospitalier et Universitaire (CHU), Toulouse, France
- Centre Hospitalier et Universitaire, Université Paul Sabatier Toulouse III, Toulouse, France
- Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), INSERM UMR1043-CNRS 5282, Toulouse, France
- *Correspondence: Arnaud Del Bello,
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13
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Yin S, Tan Q, Yang Y, Zhang F, Song T, Fan Y, Huang Z, Lin T, Wang X. Transplant outcomes of 100 cases of living-donor ABO-incompatible kidney transplantation. Chin Med J (Engl) 2022; 135:2303-2310. [PMID: 36103981 PMCID: PMC9771334 DOI: 10.1097/cm9.0000000000002138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Indexed: 01/26/2023] Open
Abstract
BACKGROUND Although ABO-incompatible (ABOi) kidney transplantation (KT) has been performed successfully, a standard preconditioning regimen has not been established. Based on the initial antidonor ABO antibody titers, an individualized preconditioning regimen is developed, and this study explored the efficacy and safety of the regimen. METHODS From September 1, 2014, to September 1, 2020, we performed 1668 consecutive living-donor KTs, including 100 ABOi and 1568 ABO-compatible (ABOc) KTs. ABOi KT recipients (KTRs) with a lower antibody titer (≤1:8) were administered oral immunosuppressive drugs (OIs) before KT, while patients with a medium titer (1:16) received OIs plus antibody-removal therapy (plasma exchange/double-filtration plasmapheresis), patients with a higher titer (≥1:32) were in addition received rituximab (Rit). Competing risk analyses were conducted to estimate the cumulative incidence of infection, acute rejection (AR), graft loss, and patient death. RESULTS After propensity score analyses, 100 ABOi KTRs and 200 matched ABOc KTRs were selected. There were no significant differences in graft and patient survival between the ABOi and ABOc groups (P = 0.787, P = 0.386, respectively). After using the individualized preconditioning regimen, ABOi KTRs showed a similar cumulative incidence of AR (10.0% υs . 10.5%, P = 0.346). Among the ABOi KTRs, the Rit-free group had a similar cumulative incidence of AR ( P = 0.714) compared to that of the Rit-treated group. Multivariate competing risk analyses revealed that a Rit-free regimen reduced the risk of infection (HR: 0.31; 95% CI: 0.12-0.78, P = 0.013). Notably, antibody titer rebound was more common in ABOi KTRs receiving a Rit-free preconditioning regimen ( P = 0.013) than those receiving Rit. ABOi KTRs with antibody titer rebound had a 2.72-fold risk of AR (HR: 2.72, 95% CI: 1.01-7.31, P = 0.048). ABOi KTRs had similar serum creatinine and estimated glomerular filtration rate compared to those of ABOc KTRs after the first year. CONCLUSIONS An individualized preconditioning regimen can achieve comparable graft and patient survival rates in ABOi KT with ABOc KT. Rit-free preconditioning effectively prevented AR without increasing the risk of infectious events in those with lower initial titers; however, antibody titer rebound should be monitored.
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Affiliation(s)
- Saifu Yin
- Department of Urology, Institute of Urology, Organ Transplantation Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Qiling Tan
- The Third Comprehensive Care Unit, West China Hospital, West China School of Nursing, Sichuan University, Chengdu, Sichuan 610041, China
| | - Youmin Yang
- Department of Urology, Institute of Urology, Organ Transplantation Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Fan Zhang
- Department of Urology, Institute of Urology, Organ Transplantation Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Turun Song
- Department of Urology, Institute of Urology, Organ Transplantation Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Yu Fan
- Department of Urology, Institute of Urology, Organ Transplantation Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Zhongli Huang
- Department of Urology, Institute of Urology, Organ Transplantation Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Tao Lin
- Department of Urology, Institute of Urology, Organ Transplantation Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Xianding Wang
- Department of Urology, Institute of Urology, Organ Transplantation Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
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14
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Begum NAS, Kashem TS, Nobi F, Arefin SUZ, Rashid HU. Experiences of performing ABO-incompatible kidney transplantation in Bangladesh. KOREAN JOURNAL OF TRANSPLANTATION 2022; 36:111-118. [PMID: 35919197 PMCID: PMC9296974 DOI: 10.4285/kjt.22.0014] [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: 03/28/2022] [Revised: 04/27/2022] [Accepted: 04/27/2022] [Indexed: 11/30/2022] Open
Abstract
Background The number of end-stage renal disease (ESRD) patients is increasing in Bangladesh. Currently, living kidney donation is the only viable option for transplantation in Bangladesh, and it is further restricted by ABO compatibility issues. We have performed ABO-incompatible kidney transplantations (ABOi KTs) in Bangladesh since 2018. This study examines our experiences with seven cases of ABOi KT. Methods The desensitization protocol included low-dose rituximab (100 mg/body) followed by plasma exchange (PEX), which was followed by a 5-g dose of intravenous immunoglobulin. Immunosuppression was undertaken using tacrolimus (0.1 mg/kg/day), mycophenolate mofetil (1,500 mg/day), and prednisolone (0.5 mg/kg/day). All patients received basiliximab for induction therapy. Results The median baseline anti-ABO antibody titer was 164 (range, 132–1128). Transplantation was performed at a titer of ≤18. Our patients attended three to five PEX sessions before transplantation. Graft survival was 100% in the seven cases over a mean period of 22 months. The mean creatinine level was 204.6±47.4 µmol/L. Two patients were suspected of having developed acute rejection and received intravenous methylprednisolone, resulting in improved kidney function. One patient required posttransplant hemodialysis due to delayed graft function and subsequently improved. Infection was the most common complication experienced by ABOi KT patients. Two patients developed severe cytomegalovirus pneumonia and died with functioning grafts. Conclusions ABOi KT in Bangladesh will substantially expand the living kidney donor pool and bring hope to a large number of ESRD patients without ABO-compatible donors. However, the high cost and risk of acute rejection and infection remain major concerns.
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Affiliation(s)
- Nura Afza Salma Begum
- Department of Nephrology, Kidney Foundation Hospital and Research Institute, Dhaka, Bangladesh
| | - Tasnuva Sarah Kashem
- Department of Nephrology, Kidney Foundation Hospital and Research Institute, Dhaka, Bangladesh
| | - Farnaz Nobi
- Department of Nephrology, Kidney Foundation Hospital and Research Institute, Dhaka, Bangladesh
| | - Shakib Uz-Zaman Arefin
- Department of Nephrology, Kidney Foundation Hospital and Research Institute, Dhaka, Bangladesh
| | - Harun Ur Rashid
- Department of Nephrology, Kidney Foundation Hospital and Research Institute, Dhaka, Bangladesh
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15
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Infection Risk in the First Year After ABO-incompatible Kidney Transplantation: A Nationwide Prospective Cohort Study. Transplantation 2022; 106:1875-1883. [PMID: 35389968 DOI: 10.1097/tp.0000000000004109] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND ABO-incompatible (ABOi) kidney transplantation (KT) expands the kidney donor pool and may help to overcome organ shortage. Nonetheless, concerns about infectious complications associated with ABOi-KT have been raised. METHODS In a nationwide cohort (Swiss Transplant Cohort Study), we compared the risk for infectious complications among ABOi and ABO-compatible (ABOc) renal transplant recipients. Infections needed to fulfill rigorous, prespecified criteria to be classified as clinically relevant. Unadjusted and adjusted competing risk regression models were used to compare the time to the first clinically relevant infection among ABOi-KT and ABOc-KT recipients. Inverse probability weighted generalized mixed-effects Poisson regression was used to estimate incidence rate ratios for infection. RESULTS We included 757 living-donor KT recipients (639 ABOc; 118 ABOi) and identified 717 infection episodes. The spectrum of causative pathogens and the anatomical sites affected by infections were similar between ABOi-KT and ABOc-KT recipients. There was no significant difference in time to first posttransplant infection between ABOi-KT and ABOc-KT recipients (subhazard ratio, 1.24; 95% confidence interval [CI], 0.93-1.66; P = 0.142). At 1 y, the crude infection rate was 1.11 (95% CI, 0.93-1.33) episodes per patient-year for ABOi patients and 0.94 (95% CI, 0.86-1.01) for ABOc-KT recipients. Inverse probability weighted infection rates were similar between groups (adjusted incidence rate ratio, 1.12; 95% CI, 0.83-1.52; P = 0.461). CONCLUSIONS The burden of infections during the first year posttransplant was high but not relevantly different in ABOi-KT and ABOc-KT recipients. Our results highlight that concerns regarding infectious complications should not affect the implementation of ABOi-KT programs.
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16
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Clinical Outcomes of Everolimus With Reduced-Dose Tacrolimus vs Mycophenolate Mofetil With Standard-Dose Tacrolimus in De Novo ABO-Incompatible Kidney Transplant Recipients: 1-Year Follow-up. Transplant Proc 2022; 54:293-298. [PMID: 35031117 DOI: 10.1016/j.transproceed.2021.08.062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Accepted: 08/26/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND One of the major barriers for long-term renal graft survival is considered to be calcineurin inhibitor nephrotoxicity, contributing to chronic graft dysfunction. Thus, recent immunosuppressive strategies are focused on regimens that can reduce or avoid exposure to calcineurin inhibitors. Herein, we carried out a small-scale pilot study to assess whether everolimus (EVR) with reduced-dose tacrolimus (Tac) is an acceptable immunosuppressive regimen for patients with de novo ABO-incompatible kidney transplant compared with mycophenolate mofetil (MMF) with standard-dose Tac. METHODS This retrospective single-center cohort study included patients who underwent ABO-incompatible kidney transplant at our institution between January 2016 and December 2019. Those whose immunosuppressive regimen was changed by reasons other than rejection during the 1-year follow-up period were excluded. RESULTS A total of 24 patients were enrolled in this study: 10 patients who received an EVR with reduced-dose Tac regimen and 14 patients who received an MMF with standard-dose Tac regimen. Tac trough levels in the EVR group were significantly lower than those in the MMF group (P < .001). No patients died or lost their grafts during the follow-up period. There were no significant differences in renal function, proteinuria, and prevalence of hyperlipidemia between the 2 groups at 1 year after transplant. There were no significant differences in the incidence of rejection (acute cellular rejection, steroid-resistant acute cellular rejection, acute antibody-mediated rejection) and infection (cytomegalovirus viremia, cytomegalovirus disease, BK viremia, BK virus nephropathy) between the 2 groups. CONCLUSIONS Comparable with MMF with standard-dose Tac, EVR with reduced-dose Tac might be an acceptable immunosuppressive regimen for patients with de novo ABO-incompatible kidney transplant.
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Jha P, Bansal S, Rana A, Nandwani A, Kher A, Sethi S, Jain M, Bansal D, Yadav D, Gadde A, Mahapatra A, Sodhi P, Ahlawat R, Kher V. ABO-incompatible kidney transplantation in India: A single-center experience of first hundred cases. Indian J Nephrol 2022; 32:42-46. [PMID: 35283580 PMCID: PMC8916160 DOI: 10.4103/ijn.ijn_465_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 10/24/2020] [Accepted: 11/30/2020] [Indexed: 11/04/2022] Open
Abstract
Aim: Material and Methods: Results: Conclusion:
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18
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Gaur L, Bhalla A, Shingada A, Gupta A, Malik M, Gupta A, Bhargava V, Gupta P, Joshi A, Jauhari H, Ranjan V, Khillan K, Rana DS. Outcomes of ABO-Incompatible kidney transplantation with respect to baseline isoagglutinin immunoglobulin G titers: A retrospective observational study. INDIAN JOURNAL OF TRANSPLANTATION 2022. [DOI: 10.4103/ijot.ijot_64_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Mohamed M, Sweeney T, Alkhader D, Nassar M, Alqassieh A, Lakhdar S, Nso N, Fülöp T, Daoud A, Soliman KM. ABO incompatibility in renal transplantation. World J Transplant 2021; 11:388-399. [PMID: 34631470 PMCID: PMC8465511 DOI: 10.5500/wjt.v11.i9.388] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2021] [Revised: 05/19/2021] [Accepted: 09/01/2021] [Indexed: 02/06/2023] Open
Abstract
ABO blood group incompatibility (ABO-I) was historically considered an absolute contraindication to kidney transplantation due to the significant risk of acute antibody-mediated rejection and early graft loss. Nevertheless, the urge to minimize the gap between the candidates’ number on the waitlist for kidney transplants and the available kidney donors encourage investigation into finding ways to use organs from ABO-I kidney donors, especially in the era of using more potent immunosuppression therapies. This review aims to discuss a general overview of ABO-I kidney transplantation and the different protocols adopted by some transplant centers to meaningfully overcome this barrier.
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Affiliation(s)
- Mahmoud Mohamed
- Department of Medicine, North Mississippi Medical Center, Tupelo, MS 38804, United States
| | - Tara Sweeney
- Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, United States
| | - Duaa Alkhader
- Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, United States
| | - Mahmoud Nassar
- Department of Medicine, Icahn School of Medicine at Mount Sinai, NYC Health and Hospitals, Queens, New York, NY 11432, United States
| | - Ahmed Alqassieh
- Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, United States
| | - Sofia Lakhdar
- Department of Medicine, Icahn School of Medicine at Mount Sinai, NYC Health and Hospitals, Queens, New York, NY 11432, United States
| | - Nso Nso
- Department of Medicine, Icahn School of Medicine at Mount Sinai, NYC Health and Hospitals, Queens, New York, NY 11432, United States
| | - Tibor Fülöp
- Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, United States
| | - Ahmed Daoud
- Department of Medicine, Kasr Alainy Medical School, Cairo University, Cairo 11562, Egypt
| | - Karim M Soliman
- Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, United States
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Lee HR, Kim K, Lee SW, Song JH, Lee JH, Hwang SD. Effect of rituximab dose on induction therapy in ABO-incompatible living kidney transplantation: A network meta-analysis. Medicine (Baltimore) 2021; 100:e24853. [PMID: 33725841 PMCID: PMC7969271 DOI: 10.1097/md.0000000000024853] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2020] [Revised: 01/26/2021] [Accepted: 01/28/2021] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Rituximab is an induction immunosuppressant essential for ABO-incompatible kidney transplantation (ABOi KT). However, studies on its dosing, which differs among countries and transplant centers, are lacking. Therefore, we retrospectively investigated the effectiveness of the induction dose of rituximab against patient mortality, graft failure, and adverse events. METHODS We included the studies referring to at least 2 of eligible induction doses (200 mg, 200-500 mg, or 500 mg) of rituximab during ABOi KT and relevant outcomes such as patient survival, graft failure, and bacterial and viral infections. We performed direct and indirect network meta-analyses using Bayesian models and ranked different rituximab doses using generation mixed treatment comparison. Publications were retrieved using CENTRAL, MEDLINE, EMBASE, and Science Citation Index Expanded databases from 1970 to February 2020 and analyzed. The GRADE of network meta-analysis approach specified 4 levels of certainty for a given result: high, moderate, low, and very low. RESULTS Among the 4256 patients from 21 trials, glomerular filtration rate, graft loss, antibody-mediated rejection, T-cell mediated rejection, fungal infection, bacterial infection, and CMV infection did not differ among ABOi groups treated with different rituximab doses. The effect on mortality was significantly higher in rituximab 200 to 500 mg, and rituximab 500 mg groups (odds ratios [OR] 3.5, 95% CrI: 1.3-9.8, and OR 3.0, 95% CrI 1.1-9.8), but not in rituximab 20 mg group (OR 0.45, 95% CrI 0.036-2.5). The incidence of BK virus was significantly lower in the rituximab 200-mg group than in the other groups. DISCUSSION In ABO-incompatible kidney transplantation, low-dose rituximab is more efficacious than higher doses and reduces serious infection risks. Additional randomized controlled trials might be needed to confirm these findings due to small sample size.
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Affiliation(s)
- Hee Ryong Lee
- Division of Nephrology, Department of Internal Medicine, Leesin Hemodialysis and Intervention Clinic, Busan
| | - Kipyo Kim
- Division of Nephrology and Hypertension, Department of Internal Medicine, Inha University School of Medicine, Incheon, Republic of Korea
| | - Seoung Woo Lee
- Division of Nephrology and Hypertension, Department of Internal Medicine, Inha University School of Medicine, Incheon, Republic of Korea
| | - Joon Ho Song
- Division of Nephrology and Hypertension, Department of Internal Medicine, Inha University School of Medicine, Incheon, Republic of Korea
| | - Jin Ho Lee
- Division of Nephrology, Department of Internal Medicine, Leesin Hemodialysis and Intervention Clinic, Busan
| | - Seun Deuk Hwang
- Division of Nephrology and Hypertension, Department of Internal Medicine, Inha University School of Medicine, Incheon, Republic of Korea
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21
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Gan CC, Jalalonmuhali M, Nordin NZ, Abdul Wahab MZ, Yahya R, Ng KP, Tan SY, Lim SK. ABO-Incompatible Living-Donor Kidney Transplantation in a Developing Country: A Multicenter Experience in Malaysia. Transplant Proc 2021; 53:856-864. [PMID: 33487455 DOI: 10.1016/j.transproceed.2020.10.038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Accepted: 10/30/2020] [Indexed: 11/28/2022]
Abstract
Malaysia has a low deceased-donor donation rate and has not embarked on a paired kidney exchange program; therefore, ABO-incompatible and HLA-incompatible transplantation remain the main contributor to the sustainability of the national kidney transplantation (KT) program. There were 26 cases of ABO-incompatible KTs performed from 2011 to 2018 in 3 major transplant centers, namely, Hospital Kuala Lumpur, University Malaya Medical Centre, and Prince Court Medical Centre. We collected perioperative and follow-up data through June 2019. The desensitization protocol varies and is center specific: the localized Japanese protocol and Swedish protocol with a target anti-A/B isoagglutinin titer of 16 or 32 on the day of transplant. The induction and tacrolimus-based maintenance protocol was nearly identical. The median follow-up time was 62.3 months (interquartile range, 37.0-79.7). Fifteen subjects had the highest predesensitization anti-A/B titer of ≥32 (57.7%). The acute cellular rejection and antibody-mediated rejection incidence were 12.5% (3 cases) and 8.3% (2 cases), respectively. Patient, graft, and death-censored graft survival rates were 96.2%, 92.3%, and 96.0%, respectively, 1 year post-living-donor KT (LDKT) and 96.2%, 87.2%, and 90.7%, respectively, 5 years post-LDKT. Our experience shows that ABO-incompatible LDKT using a suitable desensitization technique could be a safe and feasible choice for LDKT even with varied desensitization regimens for recipients with relatively high baseline isoagglutinin titers.
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Affiliation(s)
- C C Gan
- Renal Division, Department of Medicine, Faculty of Medicine, University of Malaya, Jalan Universiti, Kuala Lumpur, Wilayah Persekutuan, Kuala Lumpur, Malaysia
| | - M Jalalonmuhali
- Renal Division, Department of Medicine, Faculty of Medicine, University of Malaya, Jalan Universiti, Kuala Lumpur, Wilayah Persekutuan, Kuala Lumpur, Malaysia
| | - N Z Nordin
- Department of Nephrology, Hospital Kuala Lumpur, Ministry of Health Malaysia, Jalan Pahang, Kuala Lumpur, Malaysia
| | - M Z Abdul Wahab
- Department of Nephrology, Hospital Kuala Lumpur, Ministry of Health Malaysia, Jalan Pahang, Kuala Lumpur, Malaysia
| | - R Yahya
- Department of Nephrology, Hospital Kuala Lumpur, Ministry of Health Malaysia, Jalan Pahang, Kuala Lumpur, Malaysia
| | - K P Ng
- Renal Division, Department of Medicine, Faculty of Medicine, University of Malaya, Jalan Universiti, Kuala Lumpur, Wilayah Persekutuan, Kuala Lumpur, Malaysia
| | - S Y Tan
- Department of Nephrology, Prince Court Medical Center, Kuala Lumpur, Malaysia
| | - S K Lim
- Renal Division, Department of Medicine, Faculty of Medicine, University of Malaya, Jalan Universiti, Kuala Lumpur, Wilayah Persekutuan, Kuala Lumpur, Malaysia.
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22
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Thukral S, Shinde N, Ray DS. Effect of Different Rituximab Doses on B Cell Count, Anti-A/B Antibody Titer, Graft Function, and Infectious Complications in ABO-Incompatible Renal Transplantation: A Prospective Study. Transplant Proc 2020; 53:970-975. [PMID: 33279260 DOI: 10.1016/j.transproceed.2020.10.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Accepted: 10/20/2020] [Indexed: 11/15/2022]
Abstract
BACKGROUND ABO-incompatible kidney transplantation (ABOiKT) has been accepted as a viable and cost-effective modality with outcomes comparable to ABO-compatible transplants, but there is a concern regarding higher infectious complications in ABOiKT because of the heightened immunosuppression. The desensitization protocol normally includes antibody removal, B cell depletion by rituximab (RTX), and immunomodulation with intravenous immunoglobulin. Efforts have been made over the years to decrease the dose of RTX in an effort to decrease the infective complications. There is limited literature about the minimum effective dose of RTX, which can cause an effective B cell depletion. This prospective study was designed to correlate the RTX dose with peripheral absolute B cell count, graft function, graft and patient survival, and infective complications. METHODS This study included 52 adult ABOiKT recipients with anti-A/B antibody titer up to a maximum of 1:512. The participants were divided into 2 groups of 26 each according to the RTX dosage used: Group A received 100 mg/patient, and Group B received 200 mg/patient. RTX was given 14 days prior to transplant after B cell measurement by flow cytometry. The outcomes were compared after 1 year of follow-up. RESULTS Both the dosages effectively depleted the absolute B cell count. Although patient survivals, graft survival, graft function, acute rejection episodes, and post-transplant hospital stay were similar in both groups, infective complications were significantly higher in group B. CONCLUSION A low dose (100 mg/patient) of RTX produces effective depletion of B cells while lowering the infective complications in ABOiKT.
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Affiliation(s)
- Sharmila Thukral
- Nephrology and Renal Transplantation, Rabindranath Tagore Hospital (Narayana Health), Kolkata, India
| | - Nikhil Shinde
- Department of Nephrology, Kokilaben Dhirubhai Ambani Hospital, Mumbai, India
| | - Deepak Shankar Ray
- Nephrology Division, Rabindranath Tagore Hospital (Narayana Health), Kolkata, India.
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23
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Naciri Bennani H, Noble J, Chevallier E, Terrec F, Motte L, Giroux-Lathuile C, Bugnazet M, Imerzoukene F, Janbon B, Malvezzi P, Rostaing L, Jouve T. Isoagglutinin removal by plasma centrifugation or filtration (single or double): A prospective study in a single center. J Clin Apher 2020; 36:149-160. [PMID: 33230824 DOI: 10.1002/jca.21857] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Revised: 10/27/2020] [Accepted: 11/11/2020] [Indexed: 01/28/2023]
Abstract
INTRODUCTION ABO-incompatible (ABOi) kidney transplantation, a well-established procedure, has good long-term results provided pretransplant desensitization that includes immunosuppression and apheresis. OBJECTIVE To compare, within the first pretransplant apheresis session given to 29 ABOi kidney-transplant candidates, the effect on isoagglutinin titers (both IgG and IgM isotypes) of three modalities: centrifugation therapeutic plasmapheresis (cTP; n = 10), filtration TP (fTP; n = 9), and double-filtration plasmapheresis (DFPP; n = 10). RESULTS The three groups were comparable according to baseline demographics. Treated plasma volumes were similar across the three groups, that is, 4111 ± 403 mL (cTP), 3861 ± 282 mL (fTP), and 3699 ± 820 mL (DFPP): that is, 54 ± 7, 53 ± 7, and 53 ± 10 mL/kg respectively. One session of centrifugation or filtration TP reduced IgG anti-A/anti-B isoagglutinin titer by ~4, whereas one DFPP session reduced it by ~2. One session of cTP reduced IgM anti-A isoagglutinin titer by a little less than 4, whereas fTP and DFPP sessions reduced it by ~3. There were no statistical differences across the three groups regarding isoagglutinin rebound (IgG and IgM). However, isoagglutinin IgG rebound was >4 dilutions for anti-B titers compared with ~2 dilutions for anti-A titers. The median decreases in IgG level were -3.9 g/L (DFPP), -5.9 g/L (cTP), and - 6.06 g/L (fTP) (p = ns). Median fibrinogen depletions were ~ 60% (fTP), 64% (DFPP), and 76% (cTP). CONCLUSIONS Isoagglutinin depletions within the first apheresis session were similar across cTP, fTP, and DFPP: this was numerically lower for DFPP.
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Affiliation(s)
- Hamza Naciri Bennani
- Service de Néphrologie, Hémodialyse, Aphérèses et Transplantation Rénale, CHU Grenoble-Alpes, Grenoble, France
| | - Johan Noble
- Service de Néphrologie, Hémodialyse, Aphérèses et Transplantation Rénale, CHU Grenoble-Alpes, Grenoble, France
| | - Eloi Chevallier
- Service de Néphrologie, Hémodialyse, Aphérèses et Transplantation Rénale, CHU Grenoble-Alpes, Grenoble, France
| | - Florian Terrec
- Service de Néphrologie, Hémodialyse, Aphérèses et Transplantation Rénale, CHU Grenoble-Alpes, Grenoble, France
| | - Lionel Motte
- Service de Néphrologie, Hémodialyse, Aphérèses et Transplantation Rénale, CHU Grenoble-Alpes, Grenoble, France
| | | | - Mathilde Bugnazet
- Service de Néphrologie, Hémodialyse, Aphérèses et Transplantation Rénale, CHU Grenoble-Alpes, Grenoble, France
| | - Farida Imerzoukene
- Service de Néphrologie, Hémodialyse, Aphérèses et Transplantation Rénale, CHU Grenoble-Alpes, Grenoble, France
| | - Bénédicte Janbon
- Service de Néphrologie, Hémodialyse, Aphérèses et Transplantation Rénale, CHU Grenoble-Alpes, Grenoble, France
| | - Paolo Malvezzi
- Service de Néphrologie, Hémodialyse, Aphérèses et Transplantation Rénale, CHU Grenoble-Alpes, Grenoble, France
| | - Lionel Rostaing
- Service de Néphrologie, Hémodialyse, Aphérèses et Transplantation Rénale, CHU Grenoble-Alpes, Grenoble, France.,Université Grenoble Alpes, Grenoble, France
| | - Thomas Jouve
- Service de Néphrologie, Hémodialyse, Aphérèses et Transplantation Rénale, CHU Grenoble-Alpes, Grenoble, France.,Université Grenoble Alpes, Grenoble, France
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24
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Langhorst C, Ganner A, Schneider J, Prager EP, Walz G, Pisarski P, Jänigen B, Zschiedrich S. Long-term Follow-up of ABO-Incompatible Kidney Transplantation in Freiburg, Germany: A Single-Center Outcome Report. Transplant Proc 2020; 53:848-855. [PMID: 33041078 DOI: 10.1016/j.transproceed.2020.09.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Revised: 08/11/2020] [Accepted: 09/06/2020] [Indexed: 11/15/2022]
Abstract
BACKGROUND ABO-incompatible kidney transplantation (ABOi-KT) is an established way to enlarge the donor pool around the world. Comparability of long-term success and complications to ABO-compatible kidney transplantation (ABOc-KT) are still under debate. METHODS We evaluated all patients with a living donor kidney transplantation performed between April 1, 2004, and March 31, 2019. RESULTS A total of 137 ABOi-KT and 346 ABOc-KT were analyzed. We excluded 4 ABOi-KT recipients and 178 ABOc-KT recipients with cyclosporine A-based immunosuppression or without basiliximab induction. Three patients of the ABOi-KT cohort and 6 patients of the ABOc-KT cohort were lost to follow-up and therefore excluded. The patient characteristics were comparable except for the higher age of transplant recipients in the ABOc-KT cohort and longer follow-up of the ABOi-KT cohort. The mean estimated 15-year recipient survival was 89% in the ABOi-KT cohort and 91% in the ABOc-KT cohort (P = .39). Mean estimated graft survival was 71% in the ABOi-KT cohort and 87% in the ABOc-KT cohort (P = .68). The estimated glomerular filtration rate (Modification of Diet in Renal Disease) measured in the last follow-up was 51 mL/min/1.73 m2 in the ABOi-KT cohort and 50 mL/min/1.73 m2 in the ABOc-KT cohort (P = .36). The incidence for antibody-mediated rejection, T cell-mediated rejections, and infectious complications requiring hospitalization was not different between the cohorts. In the ABOi-KT cohort, we found significantly more lymphoceles and consequent surgical revision procedures. CONCLUSIONS At our center, ABOi-KT has as good long-term results as ABOc-KT in terms of patient survival, graft survival, and complications, with the exception of increased lymphocele formation.
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Affiliation(s)
- Christina Langhorst
- Department of Nephrology and Primary Care, Medical Centre, University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Athina Ganner
- Department of Nephrology and Primary Care, Medical Centre, University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Johanna Schneider
- Department of Nephrology and Primary Care, Medical Centre, University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Eric Peter Prager
- Department of Nephrology and Primary Care, Medical Centre, University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Gerd Walz
- Department of Nephrology and Primary Care, Medical Centre, University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Przemyslaw Pisarski
- Faculty of Medicine, University of Freiburg, Freiburg, Germany; Department of General and Digestive Surgery, Medical Centre, University of Freiburg, Freiburg, Germany
| | - Bernd Jänigen
- Faculty of Medicine, University of Freiburg, Freiburg, Germany; Department of General and Digestive Surgery, Medical Centre, University of Freiburg, Freiburg, Germany
| | - Stefan Zschiedrich
- Faculty of Medicine, University of Freiburg, Freiburg, Germany; Renal Division, Department of Internal Medicine, Bürgerspital Solothurn, Solothurn, Switzerland.
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25
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Ko Y, Kim JY, Kim SH, Kim DH, Lim SJ, Shin S, Kim YH, Jung JH, Park SK, Kwon H, Han DJ. Acute Rejection and Infectious Complications in ABO- and HLA-Incompatible Kidney Transplantations. Ann Transplant 2020; 25:e927420. [PMID: 33020465 PMCID: PMC7547531 DOI: 10.12659/aot.927420] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Background Patients receiving ABO-incompatible (ABOi) or human leukocyte antigen (HLA)-incompatible (HLAi) kidney transplantation (KT) require potent immunosuppression and are thus at a higher risk of infectious complications. We evaluated the clinical outcomes of KT stratified by ABO and HLA incompatibilities and identified the factors associated with the clinical outcomes. Material/Methods Recipients who underwent living-related KT between 2012 and 2017 were included and classified into 4 groups: ABO-compatible and HLA-compatible (ABOc/HLAc), HLA-incompatible (ABOc/HLAi), ABO-incompatible (ABOi/HLAc), and ABO-incompatible and HLA-incompatible (ABOi/HLAi). Cox proportional hazards regression analyses were carried out to evaluate the risk factors of acute rejection. Out of the 1732 patients who underwent KT, 1190, 131, 358, and 53 were in the ABOc/HLAc, ABOi/HLAc, ABOc/HLAi, and ABOi/HLAi groups, respectively. Results The ABO/HLAi group showed the lowest 5-year graft survival rate (91.7%). Death-censored graft survival was not significantly different among the groups. The mortality rate from infections was significantly higher in the ABOi/HLAi group (7.5%) than the other groups. Antibody-mediated rejection-free graft survival was the lowest in the ABOi/HLAi group, with significant differences compared with the ABOi/HLAc group (P=0.02) and the ABOc/HLAi group (P=0.03). ABOi/HLAi (hazard ratio [HR], 2.63; 95% confidence interval [CI], 1.04–6.65; P<0.01) and combined infection (HR, 1.91; 95% CI, 1.45–2.51; P<0.01) were significant risk factors for acute rejection. Conclusions Patients with both ABO and HLA incompatibilities showed inferior rates of overall patient and graft survival due to infectious complications. Infection was a prominent risk factor of acute rejection following KT after adjusting for possible confounders including ABO and HLA incompatibility.
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Affiliation(s)
- Youngmin Ko
- Division of Kidney and Pancreas Transplant Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Jee Yeon Kim
- Division of Kidney and Pancreas Transplant Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Sung-Han Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Dong Hyun Kim
- Division of Kidney and Pancreas Transplant Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Seong Jun Lim
- Division of Kidney and Pancreas Transplant Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Sung Shin
- Division of Kidney and Pancreas Transplant Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Young Hoon Kim
- Division of Kidney and Pancreas Transplant Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Joo Hee Jung
- Division of Kidney and Pancreas Transplant Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Su-Kil Park
- Division of Nephrology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Hyunwook Kwon
- Division of Kidney and Pancreas Transplant Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Duck Jong Han
- Division of Kidney and Pancreas Transplant Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
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26
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Cen M, Wang R, Kong W, Deng H, Lei W, Chen J. ABO-incompatible living kidney transplantation. Clin Transplant 2020; 34:e14050. [PMID: 32713064 DOI: 10.1111/ctr.14050] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Revised: 07/15/2020] [Accepted: 07/20/2020] [Indexed: 12/19/2022]
Abstract
ABO-incompatible living kidney transplantation is nowadays a routine procedure to expand living donor pool. The past decades have seen the evolution of desensitization protocol and immunosuppression regimen. Despite increased bleeding events, infectious complications, and rejection episodes reported in some studies, favorable graft and patient survival rate are now achieved, regardless of various protocols among transplant centers. Several issues such as the usage of rituximab and standardization of blood group antibody titration remain to be settled. The deposition of C4d is no longer the histopathologic hallmark of antibody-mediated rejection, which have inspired innovative strategies of peripheral molecular screening and the improvement of histological diagnosis of AMR (antibody-mediated rejection). The better understanding of the underlying mechanism might facilitate the distinction and therapeutic schemes of AMR.
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Affiliation(s)
- Menger Cen
- Kidney Disease Center, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Rending Wang
- Kidney Disease Center, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Weiwei Kong
- Kidney Disease Center, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Hao Deng
- Kidney Disease Center, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Wenhua Lei
- Kidney Disease Center, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Jianghua Chen
- Kidney Disease Center, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
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27
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Salvadori M, Tsalouchos A. Current protocols and outcomes of ABO-incompatible kidney transplantation. World J Transplant 2020; 10:191-205. [PMID: 32844095 PMCID: PMC7416363 DOI: 10.5500/wjt.v10.i7.191] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2020] [Revised: 05/17/2020] [Accepted: 05/29/2020] [Indexed: 02/06/2023] Open
Abstract
One of the principal obstacles in transplantation from living donors is that approximately 30% are immunologically incompatible because of the presence in the recipient of antibodies directed against the human leukocyte antigen system of the donor or because of the incompatibility of the ABO system. The aim of this review is to describe the more recent data from the literature on the different protocols used and the clinical outcomes of ABO-incompatible kidney transplantation. Two different strategies are used to overcome these barriers: desensitization of the recipient to remove the antibodies and to prevent their rebound after transplantation and the exchange of organs between two or more pairs. The largest part of this review is dedicated to describing the techniques of desensitization. Even if the first reports of successful renal transplantation between ABO-incompatible pairs have been published by 1980, the number of ABO-incompatible transplants increased substantially in this century because of our improved knowledge of the immune system and the availability of new drugs. Rituximab has substantially replaced splenectomy. The technique of apheresis has improved and more recently a tailored desensitization proved to be the more efficient strategy avoiding an excess of immunosuppression with the related side effects. Recent reports document outcomes for such transplantation similar to the outcomes of standard transplantation.
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Affiliation(s)
- Maurizio Salvadori
- Department of Transplantation Renal Unit, Careggi University Hospital, Florence 50139, Italy
| | - Aris Tsalouchos
- Nephrology and Dialysis Unit, Saints Cosmas and Damian Hospital, Pescia 51017, Italy
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28
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Abstract
Sensitization to human leukocyte antigens (HLAs) has been one of the major clinical challenges for successful kidney transplantation. In end-stage renal disease, kidney transplantation provides benefits compared with dialysis in terms of improved patient survival better quality of life, and lower ongoing costs after the first year. Living donor kidney transplantation has an advantage with improved allograft survival, and performed earlier and electively compared with deceased donor transplantation. However sensitized patients are increasing in number on transplant waiting lists, and their prospect of getting a transplant is less than nonsensitized patients due to immunological incompatibility with the donor. Strategy for sensitized patients are listing for a compatible deceased donor transplant or, if they have a living donor, either selecting a kidney exchange program or undergoing a desensitization procedure. Desensitization procedures may be undertaken to increase access to either living or deceased donor transplants, and in some situations may also be employed to facilitate participation in a kidney exchange, in less immunological barrier to be overcome. The question of whether individuals are better off with a desensitization treatment followed by HLA-incompatible living donor transplantation or waiting on the deceased donor kidney transplant list for a compatible transplant has recently been addressed by two large multicenter studies, with conflicting results. A multicenter study from the United States published in the New England Journal of Medicine [365;318 326.2011] concluded that there was a strong survival benefit for sensitized patients undergoing desensitization followed by HLA-incompatible living donor kidney transplant compared with those remaining on the waiting list. Of interest, a second study, published in the Lancet, [389;727 734.2017] found no significant survival advantage for desensitized patients compared with similar patients remaining on the waiting list in the United Kingdom. Controversies still remain regarding how desensitization can be achieved and which techniques are effective and safe. In this chapter various complications from the desensitization will be dealt with in current use of medications or armamentum.
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29
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Jeon HJ, Lee JG, Kim K, Jang JY, Han SW, Choi J, Ryu JH, Koo TY, Jeong JC, Lee JW, Ishida H, Park JB, Lee SH, Ahn C, Yang J. Peripheral blood transcriptome analysis and development of classification model for diagnosing antibody-mediated rejection vs accommodation in ABO-incompatible kidney transplant. Am J Transplant 2020; 20:112-124. [PMID: 31373158 DOI: 10.1111/ajt.15553] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2018] [Revised: 07/02/2019] [Accepted: 07/28/2019] [Indexed: 02/07/2023]
Abstract
The major obstacle to successful ABO blood group-incompatible kidney transplantation (ABOi KT) is antibody-mediated rejection (AMR). This study aimed to investigate transcriptional profiles through RNA sequencing and develop a minimally invasive diagnostic tool for discrimination between accommodation and early acute AMR in ABOi KT. Twenty-eight ABOi KT patients were selected: 18 with accommodation and 10 with acute AMR at the 10th day posttransplant protocol biopsy. Complete transcriptomes of their peripheral blood were analyzed by RNA sequencing. Candidate genes were selected by bioinformatics analysis, validated with quantitative polymerase chain reaction, and used to develop a classification model to diagnose accommodation. A total of 1385 genes were differentially expressed in accommodation compared with in AMR with P-adjusted < .05. Functional annotation and gene set enrichment analysis identified several immune-related and immunometabolic pathways. A 5-gene classification model including COX7A2L, CD69, CD14, CFD, and FOXJ3 was developed by logistic regression analysis. The model was further validated with an independent cohort and discriminated between accommodation and AMR with 92.7% sensitivity, 85.7% specificity, and 91.7% accuracy. Our study suggests that a classification model based on peripheral blood transcriptomics may allow minimally invasive diagnosis of acute AMR vs accommodation and subsequent patient-tailored immunosuppression in ABOi KT.
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Affiliation(s)
- Hee Jung Jeon
- Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea
| | - Jae-Ghi Lee
- Transplantation Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Kwangsoo Kim
- Division of Clinical Bioinformatics, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
| | - Joon Young Jang
- Transplantation Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Sung Won Han
- School of Industrial Management Engineering, Korea University, Seoul, Republic of Korea
| | - Jinwoo Choi
- School of Industrial Management Engineering, Korea University, Seoul, Republic of Korea
| | - Jung-Hwa Ryu
- Transplantation Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Tai Yeon Koo
- Transplantation Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Jong Cheol Jeong
- Department of Nephrology, Ajou University School of Medicine, Suwon, Gyeonggi-do, Republic of Korea
| | - Jae Wook Lee
- Nephrology Clinic, National Cancer Center, Goyang, Gyeonggi-do, Republic of Korea
| | - Hideki Ishida
- Department of Urology, Tokyo Women's Medical University, Tokyo, Japan
| | - Jae Berm Park
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Sang Ho Lee
- Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Curie Ahn
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jaeseok Yang
- Transplantation Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.,Transplantation Center, Seoul National University Hospital, Seoul, Republic of Korea.,Department of Surgery, Seoul National University Hospital, Seoul, Republic of Korea
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Uchida J, Kosoku A, Naganuma T, Tanaka T, Nakatani T. Latest insights on ABO-incompatible living-donor renal transplantation. Int J Urol 2019; 27:30-38. [PMID: 31522462 PMCID: PMC7004137 DOI: 10.1111/iju.14109] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Accepted: 08/23/2019] [Indexed: 12/13/2022]
Abstract
This review summarizes the latest insights on ABO‐incompatible living‐donor renal transplantation. Desensitization protocols and clinical outcomes were investigated, and a comparison was made with kidney‐paired donation, which is not permitted in Japan for ethical reasons. Although renal transplantation is greatly beneficial for most patients with end‐stage kidney disease, many of these patients must remain on dialysis therapy for extended periods due to the scarcity of organs from deceased donors. ABO blood type incompatibility was once believed to be a contraindication to renal transplantation due to the increased risk for antibody‐mediated rejection and early graft loss attributable to isoagglutinins. Recently, pretransplant desensitization strategies, such as removal of isoagglutinins and antibody‐producing cells, have achieved successful outcomes, although it remains unclear whether graft survival and patient morbidity are equivalent to those for ABO‐compatible renal transplantation. The present review suggested that ABO‐incompatible living‐donor renal transplantation might be a favorable radical renal replacement therapy for patients with end‐stage kidney disease.
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Affiliation(s)
- Junji Uchida
- Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Akihiro Kosoku
- Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Toshihide Naganuma
- Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Tomoaki Tanaka
- Department of Urology, Suita Municipal Hospital, Suita, Japan
| | - Tatsuya Nakatani
- Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan
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Kakuta Y, Okumi M, Unagami K, Iizuka J, Takagi T, Ishida H, Tanabe K. Outcomes, complications, and economic impact of ABO-incompatible living kidney transplantation: A single-center Japanese cohort study. Clin Transplant 2019; 33:e13591. [PMID: 31077450 DOI: 10.1111/ctr.13591] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2019] [Revised: 04/24/2019] [Accepted: 05/06/2019] [Indexed: 01/02/2023]
Abstract
ABO-incompatible kidney transplantation (ABO-ILKT) has been reported to have a higher rate of early complications and higher medical costs than ABO-compatible kidney transplantation (ABO-CLKT). We aimed to compare the clinical outcomes, complications, and medical costs between ABO-ILKTs and ABO-CLKTs at 2 years post-transplantation. We included 65 ABO-ILKTs and 94 ABO-CLKTs in this retrospective analysis. The patient survival, graft survival, rejection incidence, and graft function were similar between ABO-CLKT and ABO-ILKT. The hospitalization costs for ABO-CLKT and ABO-ILKT were 26 544 ± 4168 USD and 34 906 ± 18 732 USD, respectively (P = 0.0001). Total 2-year medical costs were 77 117 ± 15 609 USD and 85 325 ± 33 997 USD for ABO-CLKT and ABO-ILKT, respectively, indicating that the medical costs of ABO-ILKT recipients were non-significantly higher than those of ABO-CLKT recipients at 2 years post-transplantation (P = 0.0866). ABO-ILKT and ABO-CLKT recipients showed similar infectious adverse events and complications. In conclusion, medical cost at 2 years post-transplantation, including transplant hospitalization cost, and the frequency of early complications were not significantly higher in the ABO-ILKT group than in the ABO-CLKT group. ABO-ILKT is an acceptable treatment for patients with ESRD and is comparable to ABO-CLKT not only in terms of outcomes but also in terms of medical cost.
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Affiliation(s)
- Yoichi Kakuta
- Department of Urology, Tokyo Women's Medical University, Tokyo, Japan
| | - Masayoshi Okumi
- Department of Urology, Tokyo Women's Medical University, Tokyo, Japan
| | - Kohei Unagami
- Department of Organ Transplant Medicine, Tokyo Women's Medical University, Tokyo, Japan
| | - Junpei Iizuka
- Department of Urology, Tokyo Women's Medical University, Tokyo, Japan
| | - Toshio Takagi
- Department of Urology, Tokyo Women's Medical University, Tokyo, Japan
| | - Hideki Ishida
- Department of Organ Transplant Medicine, Tokyo Women's Medical University, Tokyo, Japan
| | - Kazunari Tanabe
- Department of Urology, Tokyo Women's Medical University, Tokyo, Japan
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32
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Agrawal S, Chowdhry M, Makroo RN, Nayak S, Gajulapalli SP, Thakur UK, Agrawal A. Therapeutic Immunoadsorption and Conventional Plasma Exchange in ABO-incompatible Renal Transplant: An Exculpatory Evidence. Cureus 2019; 11:e4787. [PMID: 31367505 PMCID: PMC6666925 DOI: 10.7759/cureus.4787] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Aim The objective of this study was to compare the efficacy of immunoadsorption (IA) with conventional therapeutic plasma-exchange (cTPE) in ABO-incompatible (ABOi) renal transplant. Methods Data of patients from July 2015 to June 2017 (category-I, number of patients (N) = 11; IA±cTPE) on the average length of stay (ALOS), number of cTPE/IA, antibody-titers (AT), creatinine, patient and graft survival at one year were compared retrospectively with patients in period from February 2012 to June 2015 (category-II, N = 29; cTPE only). AT of patients not decreasing to less than one fold after two cTPE were shifted for IA. For patients undergoing IA, real-time AT was done and IA stopped after target titer (TT <1:8) was achieved. Post-transplant cTPE was done if, titers rebounded to ≥1:8. Intravenous immunoglobulin (IVIG) was given after every cTPE/IA. Cost comparisons were made. Results In category-I, seven patients (63.63%) were shifted to IA from cTPE. The mean cTPE procedures in category I and II are 3.5 ± 2.4 and 4.8 ± 2.5, respectively (p = 0.206). The mean IA procedures in category-I are 1.6 ± 0.5. The number of patients requiring post-operative TPE was less in category-I than category-II, i.e., N = 5, 45.5% vs N = 20, 69%, respectively (p = 0.171). The expense of IA in category-I vs cTPE in category-II was statistically not significant (p = 0.422) but had significant lesser ALOS (p = 0.044). Expenses, when a patient undergoes both cTPE and IA (category-I), are significantly higher to category-II (p = 0.003). The two groups were comparable in AT, creatinine value, graft and patient survival rates at one year. Conclusion Contrary to the general judgment of IA being expensive than cTPE, this study shows equivalent expenditures with comparable therapeutic outcomes.
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Affiliation(s)
- Soma Agrawal
- Transfusion Medicine, Indraprastha Apollo Hospitals, New Delhi, IND
| | - Mohit Chowdhry
- Transfusion Medicine, Indraprastha Apollo Hospitals, New Delhi, IND
| | - Raj N Makroo
- Transfusion Medicine, Indraprastha Apollo Hospitals, New Delhi, IND
| | - Sweta Nayak
- Transfusion Medicine, Fortis Hospital, Faridabad, IND
| | | | - Uday K Thakur
- Transfusion Medicine, Indraprastha Apollo Hospitals, New Delhi, IND
| | - Ankit Agrawal
- Internal Medicine, Saint Peter's University Hospital - Rutgers Robert Wood Johnson Medical School, New Brunswick, USA
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Scurt FG, Ewert L, Mertens PR, Haller H, Schmidt BMW, Chatzikyrkou C. Clinical outcomes after ABO-incompatible renal transplantation: a systematic review and meta-analysis. Lancet 2019; 393:2059-2072. [PMID: 31006573 DOI: 10.1016/s0140-6736(18)32091-9] [Citation(s) in RCA: 89] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2018] [Revised: 08/23/2018] [Accepted: 08/28/2018] [Indexed: 12/18/2022]
Abstract
BACKGROUND ABO-incompatible renal transplantation (ABOi-rTx) is increasingly used to overcome organ shortage. Evidence about its non-inferiority in comparison with ABO-compatible renal transplantation (ABOc-rTx) needs to be analysed at early and late timepoints. We aimed to investigate differences in outcome after ABOi-rTX and ABOc-rTX. METHODS We did a systematic review and meta-analysis of observational studies published up until Dec 31, 2017, that reported outcome data (≥1 year of follow-up) after ABOi-rTx and included an ABO-compatible control group, by searching the Cochrane Central Register of Controlled Trials (CENTRAL), Embase Ovid, MEDLINE Ovid, and PubMed. Trials on recipients of ABOi-rTx were assessed, if an ABO-compatible control group was included and if outcome data on at least graft or recipient survival with 1 year or more of follow-up were available. Exclusion criteria included case reports, editorials, reviews and letters, animal studies, meeting papers, studies unable to extract data, non-renal solid organ and bone-marrow transplant studies, and deceased donor ABOc-rTx. Data were extracted from published reports. Primary endpoints were all-cause mortality and graft survival at 1, 3, 5, and more than 8 years after transplantation. In the meta-analysis, we used a fixed-effects model if the I2 value was 0, and both a fixed-effects and random-effects model if I2 was more than 0. This study is registered with PROSPERO, number CRD42018094550. FINDINGS 1264 studies were screened and 40 studies including 49 patient groups were identified. 65 063 patients were eligible for analysis, 7098 of whom had undergone ABOi-rTx. Compared with ABOc-rTx, ABOi-rTx was associated with significantly higher 1-year mortality (odds ratio [OR] 2·17 [95% CI 1·63-2·90], p<0·0001; I2=37%), 3 years (OR 1·89 [1·46-2·45], p<0·0001; I2=29%), and 5 years (OR 1·47 [1·08-2·00], p=0·010; I2=68%) following transplantation. Death-censored graft survival was lower with ABOi-rTx than with ABOc-rTx at 1 year (OR 2·52 [1·80-3·54], p<0·0001; I2=61%) and 3 years (OR 1·59 [1·15-2·18], p=0·0040; I2=58%) only. Graft losses were equivalent to that of ABOc-rTx after 5 years and patient survival after 8 years. No publication bias was detected and the results were robust to trial sequential analysis until 5 years after transplantation; thereafter, data became futile or inconclusive. INTERPRETATION Despite progress in desensitisation protocols and optimisation of ABOi-rTx procedures, excess mortality and loss of kidney grafts was found compared with ABOc-rTx within the first 3 years after transplantation. Only long-term outcomes after 5 years yielded equivalent survival rates and organ function. Awareness of the increased risks of infection, organ rejection, and bleeding could improve care of patients and promote efforts towards paired kidney exchange programmes. FUNDING None.
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Affiliation(s)
- Florian G Scurt
- Clinic of Nephrology and Hypertension, Diabetology and Endocrinology, Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany.
| | - Lara Ewert
- Clinic of Nephrology and Hypertension, Diabetology and Endocrinology, Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany
| | - Peter R Mertens
- Clinic of Nephrology and Hypertension, Diabetology and Endocrinology, Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany
| | - Hermann Haller
- Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany
| | - Bernhard M W Schmidt
- Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany
| | - Christos Chatzikyrkou
- Clinic of Nephrology and Hypertension, Diabetology and Endocrinology, Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany.
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Okumi M, Kakuta Y, Unagami K, Takagi T, Iizuka J, Inui M, Ishida H, Tanabe K. Current protocols and outcomes of ABO-incompatible kidney transplantation based on a single-center experience. Transl Androl Urol 2019; 8:126-133. [PMID: 31080772 DOI: 10.21037/tau.2019.03.05] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
ABO-incompatible living kidney transplantation (ABO-ILKT) is an effective option for increasing living kidney transplant opportunities. ABO-ILKT has been conducted in our institution since 1989 to widen the indication for living kidney transplantation. ABO-ILKT is considered to require extra treatment, and it has increased risks compared with ABO-compatible living kidney transplantation (ABO-CLKT). In the past two decades, some protocols have removed anti-blood-type antibodies to prevent the production of antibodies. Additionally, we have made considerable changes to our ABO-ILKT protocol as new immunosuppressive agents have been developed. Consequently, increased immunosuppression and immunological understanding have helped shape recent desensitization protocols. Herein, we review the history, therapeutic strategy, pathology, and future directions of ABO-ILKT. Our standard immunosuppressive regimen and desensitization protocol for ABO-ILKT recipients consist of low doses of tacrolimus (TAC), mycophenolate mofetil (MMF), and rituximab; several sessions of double filtration plasmapheresis; and basiliximab induction. We do not use thymoglobulin induction, intravenous immunoglobulin, or prophylactic post-transplant plasmapheresis. Recently, ABO-ILKT has been recognized as a useful alternative therapy for end-stage kidney disease with ABO-incompatibility, and its outcome is comparable to that of ABO-CLKT.
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Affiliation(s)
- Masayoshi Okumi
- Department of Urology, Tokyo Women's Medical University, Tokyo, Japan
| | - Yoichi Kakuta
- Department of Urology, Tokyo Women's Medical University, Tokyo, Japan
| | - Kohei Unagami
- Department of Nephrology, Tokyo Women's Medical University, Tokyo, Japan.,Department of Organ Transplant Medicine, Tokyo Women's Medical University, Tokyo, Japan
| | - Toshio Takagi
- Department of Urology, Tokyo Women's Medical University, Tokyo, Japan
| | - Junpei Iizuka
- Department of Urology, Tokyo Women's Medical University, Tokyo, Japan
| | - Masashi Inui
- Department of Urology, Tokyo Women's Medical University, Tokyo, Japan
| | - Hideki Ishida
- Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.,Department of Organ Transplant Medicine, Tokyo Women's Medical University, Tokyo, Japan
| | - Kazunari Tanabe
- Department of Urology, Tokyo Women's Medical University, Tokyo, Japan
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Infectious Complications in Adult ABO-Incompatible Liver Transplantation: Our Preliminary Experience. Int Surg 2019. [DOI: 10.9738/intsurg-d-16-00084.1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
The number of ABO-incompatible living donor liver transplantations (ABO-I LDLT) has increased owing to the use of preoperative rituximab for immunosuppression. However, controversy remains regarding adequate immunosuppression owing to rejection and infection. Here, we present 5 cases of our ABO-I LDLT experience, emphasizing rejection and infectious complications, retrospectively. The treatment protocol included prophylactic rituximab followed by plasma exchange prior to transplantation, splenectomy, and immunosuppressive and prophylactic antibiotic regimens after transplantation. Four of the 5 patients also received local infusion therapy via the portal vein. Neither hyperacute nor antibody-mediated rejection occurred. All grafts were functioning well at discharge. Rehospitalization was required for 2 patients due to severe infection within 6 months of transplantation. Invasive aspergillosis was successfully treated in 1 patient, but the other patient died from severe sepsis with overwhelming postsplenectomy infection syndrome. Our results confirm that, although improved immunosuppressive therapy markedly reduces rejection in ABO-I LDLT, it is also associated with an increased risk of various life-threatening infections.
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Shah Y, Almeshari K, Broering D, Aleid H, Brockmann J, Alhumaidan H, Hammad E, Elgamal H, Alahmadi I, Hussein M, Ibrahim I, Ali T. ABO-Incompatible Kidney Transplantation: Low Rates of Infectious Complications and Excellent Patient Survival. Transplant Proc 2019; 51:512-516. [PMID: 30879579 DOI: 10.1016/j.transproceed.2019.01.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND A significant gap exists between demand and supply of organs for patients with end-stage renal disease. To increase the donor pool, kidney transplantation is performed across ABO- and HLA-incompatible barriers. ABO-incompatible kidney transplant (ABOi-KT) recipients are at increased risk of antibody-mediated rejection, infection, and mortality. Hypogammaglobulinemia secondary to immunosuppression is highly prevalent after solid organ transplantation, and intravenous immunoglobulin (IVIG) has been reported to reduce the risks of infections in various settings. We use high-dose IVIG in ABOi-KT recipients perioperatively. We aimed to determine the rate of infectious complications along with graft and patient survival in our ABOi-KT recipients. METHODS We included all adult patients who underwent ABOi-KT from the year 2007 to 2016. Patients received rituximab, plasma exchange, and IVIG (2 g/kg body weight). Thymoglobulin and intravenous methylprednisolone were used as induction treatment. Oral prednisone, mycophenolate mofetil, and tacrolimus were used as maintenance therapy. RESULTS A total of 77 ABOi-KTs were performed, and the recipients were followed up for a median of 1557 days. Two patients were diagnosed as having BK nephropathy. No patients were diagnosed as having pneumocystis infection, cytomegalovirus disease, herpes simplex, varicella zoster, or fungal infection. One-year graft and patient survival was 94.8% and 100%, respectively. CONCLUSIONS In our series of ABOi-KTs, we observed a low risk of infectious complications and excellent patient survival. High-dose IVIG might have reduced infections.
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Affiliation(s)
- Y Shah
- King Faisal Specialist Hospital & Research Center, Department of Kidney and Pancreas Transplant, Riyadh, Saudi Arabia
| | - K Almeshari
- King Faisal Specialist Hospital & Research Center, Department of Kidney and Pancreas Transplant, Riyadh, Saudi Arabia
| | - D Broering
- King Faisal Specialist Hospital & Research Center, Department of Kidney and Pancreas Transplant, Riyadh, Saudi Arabia
| | - H Aleid
- King Faisal Specialist Hospital & Research Center, Department of Kidney and Pancreas Transplant, Riyadh, Saudi Arabia
| | - J Brockmann
- King Faisal Specialist Hospital & Research Center, Department of Kidney and Pancreas Transplant, Riyadh, Saudi Arabia
| | - H Alhumaidan
- King Faisal Specialist Hospital & Research Center, Department of Kidney and Pancreas Transplant, Riyadh, Saudi Arabia
| | - E Hammad
- King Faisal Specialist Hospital & Research Center, Department of Kidney and Pancreas Transplant, Riyadh, Saudi Arabia
| | - H Elgamal
- King Faisal Specialist Hospital & Research Center, Department of Kidney and Pancreas Transplant, Riyadh, Saudi Arabia
| | - I Alahmadi
- King Faisal Specialist Hospital & Research Center, Department of Kidney and Pancreas Transplant, Riyadh, Saudi Arabia
| | - M Hussein
- King Faisal Specialist Hospital & Research Center, Department of Kidney and Pancreas Transplant, Riyadh, Saudi Arabia
| | - I Ibrahim
- King Faisal Specialist Hospital & Research Center, Department of Kidney and Pancreas Transplant, Riyadh, Saudi Arabia
| | - T Ali
- King Faisal Specialist Hospital & Research Center, Department of Kidney and Pancreas Transplant, Riyadh, Saudi Arabia.
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Kosoku A, Uchida J, Nishide S, Kabei K, Shimada H, Iwai T, Kuwabara N, Maeda K, Naganuma T, Kumada N, Takemoto Y, Ishihara T, Shintani A, Nakatani T. ABO-incompatible kidney transplantation as a renal replacement therapy-A single low-volume center experience in Japan. PLoS One 2018; 13:e0208638. [PMID: 30596663 PMCID: PMC6312268 DOI: 10.1371/journal.pone.0208638] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2018] [Accepted: 11/20/2018] [Indexed: 12/22/2022] Open
Abstract
INTRODUCTION Living donor kidney transplantation is preferable to deceased donor transplantation due to its superior long-term patient and graft survivals. However, ABO blood group incompatibility is a major barrier to living donor kidney transplantation. ABO-incompatible kidney transplantation has been performed in Japan since the late 1980's, but it is still globally uncommon. The objective of this study is to compare the clinical outcomes of ABO-incompatible kidney transplantation (ABO-IKT) with that of ABO-compatible kidney transplantation (ABO-CKT) at an institution where only about two kidney transplants are performed a month on average. DESIGN A single center propensity score-matched cohort study. PATIENTS AND METHODS We retrospectively collected and analyzed the data of 240 patients with end-stage kidney disease (ESKD) who underwent living donor kidney transplantation at Osaka City University Hospital from January 1999 to December 2016, of which 66 patients were ABO-IKT. The remaining 174 patients who underwent ABO-CKT were studied as the control group, and the clinical outcomes of ABO-IKT and ABO-CKT recipients were compared based on propensity score matching. RESULTS After propensity score matching, there were no significant differences in both patient survival and death-censored graft survival rates between the ABO-IKT and ABO-CKT groups. Moreover, there were no significant differences in estimated glomerular filtration rate as well as frequency of acute cellular rejection, antibody-mediated rejection, infectious adverse events, malignancies, and post-operative bleeding between the two groups. CONCLUSION Currently, ABO-IKT may be an acceptable treatment for patients with ESKD even at a low-volume transplant center.
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Affiliation(s)
- Akihiro Kosoku
- Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Junji Uchida
- Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan
- * E-mail:
| | - Shunji Nishide
- Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Kazuya Kabei
- Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Hisao Shimada
- Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Tomoaki Iwai
- Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Nobuyuki Kuwabara
- Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Keiko Maeda
- Department of Nursing, Osaka City University Hospital, Osaka, Japan
| | - Toshihide Naganuma
- Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Norihiko Kumada
- Department of Urology, Suita Municipal Hospital, Suita, Japan
| | - Yoshiaki Takemoto
- Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Takuma Ishihara
- Innovative and Clinical Research Promotion Center, Gifu University Hospital, Gifu, Japan
| | - Ayumi Shintani
- Department of Medical Statistics, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Tatsuya Nakatani
- Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan
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Uchida J, Iwai T, Nishide S, Kabei K, Kuwabara N, Naganuma T, Kumada N, Takemoto Y, Nakatani T. Pilot Conversion Study From Mycophenolate Mofetil to Everolimus in Stable ABO-Incompatible Kidney Transplant Recipients: Analysis of 1-Year Follow-Up Data. EXP CLIN TRANSPLANT 2018; 17:190-195. [PMID: 30198840 DOI: 10.6002/ect.2017.0200] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Here, we report our 1-year follow-up data of stable ABO-incompatible kidney transplant recipients who converted from mycophenolate mofetil plus a standard dose of a calcineurin inhibitor to everolimus plus low exposure to calcineurin inhibitors. MATERIALS AND METHODS Our study included 17 recipients of ABO-incompatible kidney transplant procedures performed at our institution. At baseline and at 3 and 12 months after conversion, graft biopsies were performed to check for acute rejection and C4d deposition. RESULTS Treatment with everolimus was stopped due to adverse events in 8 patients (47.1%). Conversion to everolimus with calcineurin inhibitor minimization did not induce acute rejection or C4d deposition at 3 and 12 months after conversion in ABO-incompatible kidney transplant recipients in whom everolimus was maintained or stopped within 1 year after conversion. CONCLUSIONS Everolimus elicited no acute rejection and no C4d deposition, whether everolimus was maintained or stopped within 1 year after conversion, in ABO-incompatible kidney transplant recipients.
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Affiliation(s)
- Junji Uchida
- From the Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan
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de Weerd AE, Betjes MGH. ABO-Incompatible Kidney Transplant Outcomes: A Meta-Analysis. Clin J Am Soc Nephrol 2018; 13:1234-1243. [PMID: 30012630 PMCID: PMC6086717 DOI: 10.2215/cjn.00540118] [Citation(s) in RCA: 94] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Accepted: 05/03/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND OBJECTIVES ABO blood group-incompatible kidney transplantation is considered a safe procedure, with noninferior outcomes in large cohort studies. Its contribution to living kidney transplantation programs is substantial and growing. Outcomes compared with center-matched ABO blood group-compatible control patients have not been ascertained. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Comprehensive searches were conducted in Embase, Medline, Cochrane, Web-of-Science, and Google Scholar. Meta-analyses Of Observational Studies in Epidemiology study guidelines for observational studies and Newcastle Ottawa bias scale were implemented to assess studies. Meta-analysis was performed using Review Manager 5.3. A subgroup analysis on antibody removal technique was performed. RESULTS After identifying 2728 studies addressing ABO-incompatible kidney transplantation, 26 studies were included, describing 1346 unique patients who were ABO-incompatible and 4943 ABO-compatible controls. Risk of bias was low (all studies ≥7 of 9 stars). Baseline patient characteristics revealed no significant differences in immunologic risk parameters. Statistical heterogeneity of studies was low (I2 0% for graft and patient survival). One-year uncensored graft survival of patients who were ABO-incompatible was 96% versus 98% in ABO-compatible controls (relative risk, 0.97; 95% confidence interval, 0.96 to 0.98; P<0.001). Forty-nine percent of reported causes of death in patients who were ABO-incompatible were of infectious origin, versus only 13% in patients who were ABO-compatible (P=0.02). Antibody-mediated rejection (3.86; 95% confidence interval, 2.05 to 7.29; P<0.001), severe nonviral infection (1.44; 95% confidence interval, 1.13 to 1.82; P=0.003), and bleeding (1.92; 95% confidence interval, 1.36 to 2.72; P<0.001) were also more common after ABO-incompatible transplantation. CONCLUSIONS ABO-incompatible kidney transplant recipients have good outcomes, albeit inferior to center-matched ABO-compatible control patients.
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Affiliation(s)
- Annelies E de Weerd
- Department of Nephrology and Kidney Transplantation, Erasmus Medical Center, Rotterdam, The Netherlands
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Orandi BJ, Luo X, King EA, Garonzik-Wang JM, Bae S, Montgomery RA, Stegall MD, Jordan SC, Oberholzer J, Dunn TB, Ratner LE, Kapur S, Pelletier RP, Roberts JP, Melcher ML, Singh P, Sudan DL, Posner MP, El-Amm JM, Shapiro R, Cooper M, Lipkowitz GS, Rees MA, Marsh CL, Sankari BR, Gerber DA, Nelson PW, Wellen J, Bozorgzadeh A, Gaber AO, Segev DL. Hospital readmissions following HLA-incompatible live donor kidney transplantation: A multi-center study. Am J Transplant 2018; 18:650-658. [PMID: 28834181 PMCID: PMC5820188 DOI: 10.1111/ajt.14472] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2017] [Revised: 08/06/2017] [Accepted: 08/11/2017] [Indexed: 01/25/2023]
Abstract
Thirty percent of kidney transplant recipients are readmitted in the first month posttransplantation. Those with donor-specific antibody requiring desensitization and incompatible live donor kidney transplantation (ILDKT) constitute a unique subpopulation that might be at higher readmission risk. Drawing on a 22-center cohort, 379 ILDKTs with Medicare primary insurance were matched to compatible transplant-matched controls and to waitlist-only matched controls on panel reactive antibody, age, blood group, renal replacement time, prior kidney transplantation, race, gender, diabetes, and transplant date/waitlisting date. Readmission risk was determined using multilevel, mixed-effects Poisson regression. In the first month, ILDKTs had a 1.28-fold higher readmission risk than compatible controls (95% confidence interval [CI] 1.13-1.46; P < .001). Risk peaked at 6-12 months (relative risk [RR] 1.67, 95% CI 1.49-1.87; P < .001), attenuating by 24-36 months (RR 1.24, 95% CI 1.10-1.40; P < .001). ILDKTs had a 5.86-fold higher readmission risk (95% CI 4.96-6.92; P < .001) in the first month compared to waitlist-only controls. At 12-24 (RR 0.85, 95% CI 0.77-0.95; P = .002) and 24-36 months (RR 0.74, 95% CI 0.66-0.84; P < .001), ILDKTs had a lower risk than waitlist-only controls. These findings of ILDKTs having a higher readmission risk than compatible controls, but a lower readmission risk after the first year than waitlist-only controls should be considered in regulatory/payment schemas and planning clinical care.
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Affiliation(s)
- Babak J. Orandi
- Department of Surgery, University of California-San Francisco, San Francisco, CA
| | - Xun Luo
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Elizabeth A. King
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | | | - Sunjae Bae
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Robert A. Montgomery
- The NYU Transplant Institute, New York University Langone Medical Center, NY, NY
| | | | - Stanley C. Jordan
- Department of Medicine, Cedars-Sinai Comprehensive Transplant Center, Los Angeles, CA
| | - Jose Oberholzer
- Department of Surgery, University of Illinois-Chicago, Chicago IL
| | - Ty B. Dunn
- Department of Surgery, University of Minnesota, Minneapolis, MN
| | - Lloyd E. Ratner
- Department of Surgery, Columbia University Medical Center, New York, NY
| | - Sandip Kapur
- Department of Surgery, New York Presbyterian/Weill Cornell Medical Center, New York, NY
| | | | - John P. Roberts
- Department of Surgery, University of California-San Francisco, San Francisco, CA
| | | | - Pooja Singh
- Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA
| | - Debra L. Sudan
- Department of Surgery, Duke University Medical Center, Durham, NC
| | - Marc P. Posner
- Department of Surgery, Virginia Commonwealth University, Richmond, VA
| | - Jose M. El-Amm
- Integris Baptist Medical Center, Transplant Division, Oklahoma City, OK
| | - Ron Shapiro
- Recanati Miller Transplantation Institute, Mount Sinai Hospital, New York, NY
| | | | | | - Michael A. Rees
- Department of Urology, University of Toledo Medical Center, Toledo, OH
| | | | | | - David A. Gerber
- Department of Surgery, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Paul W. Nelson
- Department of Surgery, University of Nevada, Las Vegas, NV
| | - Jason Wellen
- Department of Surgery, Barnes-Jewish Hospital, St. Louis, MO
| | - Adel Bozorgzadeh
- Department of Surgery, University of Massachusetts Memorial Medical Center, Worcester, MA
| | - A. Osama Gaber
- Department of Surgery, Houston Methodist Hospital, Houston, TX
| | - Dorry L. Segev
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
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Herzog AL, Kalogirou C, Wanner C, Lopau K. Safety and Efficacy of Induction Therapy With Thymoglobulin in AB0-Incompatible Kidney Transplantation. Transplant Proc 2018; 50:53-59. [PMID: 29407331 DOI: 10.1016/j.transproceed.2017.12.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2017] [Accepted: 12/05/2017] [Indexed: 11/30/2022]
Abstract
INTRODUCTION Data suggest an additional role of T cells in antibody-mediated rejections. In 2001 a protocol for AB0-incompatible kidney transplantation based on B-cell-depleting anti-CD20 antibody rituximab, antigen-specific blood group IgG immunoadsorption, intravenous immunoglobulins, and triple immunosuppression was introduced in Europe, which used induction therapy with the use of interleukin-2 receptor antibody (IL2-RA) basiliximab. We used thymoglobulin in AB0-incompatible patients as induction in the face of high immunologic risk. METHODS We retrospectively evaluated a cohort of 9 AB0i living donation (LD) recipients from 2011 to 2014. Desensitization included blood group-specific immunoadsorption. Eighteen AB0-compatible LD recipients receiving induction therapy with thymoglobulin served as control subjects. Another control group consisted of 18 AB0-compatible LD recipients receiving basiliximab. Follow-up was 24 months. We captured graft function by estimating glomerular filtration rate (eGFR by Modification of Diet in Renal Disease formula), rejection episodes, and bacterial and viral infections. RESULTS All patients experienced immediate graft function. No significant or clinical differences were observed regarding graft function, rejection rates, or infections between the groups, although there seemed to be slightly higher cytomegalovirus infection rates due to preemptive therapy strategy. CONCLUSIONS Thymoglobulin appears to be similar in safety and efficacy to IL-2-antagonists in AB0i kidney transplantation.
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Affiliation(s)
- A L Herzog
- Division of Nephrology, Medizinische Klinik I, Transplantationszentrum, University of Würzburg, Universitätsklinikum, Würzburg, Germany.
| | - C Kalogirou
- Department of Urology and Pediatric Urology, Julius-Maximilians-University Medical School, Würzburg, Germany
| | - C Wanner
- Division of Nephrology, Medizinische Klinik I, Transplantationszentrum, University of Würzburg, Universitätsklinikum, Würzburg, Germany
| | - K Lopau
- Division of Nephrology, Medizinische Klinik I, Transplantationszentrum, University of Würzburg, Universitätsklinikum, Würzburg, Germany
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Abstract
The ‘weekend effect’ describes increased adverse outcomes after weekend hospitalization. We examined weekend-weekday differences in the outcome of 580 patients following renal transplantation (RTx, brain dead donors) between January 2007 and December 2014 at our center. 3-year patient and graft survival, incidence of delayed graft function (DGF), acute rejections and estimated glomerular filtration rate (eGFR, CKD-EPI) at 1 year as well as surgical complications were assessed. Of all 580 transplants, 416 (71.7%) were performed on weekdays (Monday-Friday) and 164 (28.3%) on weekends (Saturday-Sunday). 3-year patient and graft survival, frequencies of DGF, acute rejections and 1-year eGFR as well as length of hospital stay were similar between RTx patients transplanted on weekdays or weekends, respectively. However, a noticeable difference was detected with regard to surgical complications which were more frequent in RTx patients transplanted on weekends. All results remained consistent across all definitions of weekend status. Our results suggest that weekend transplant status does not affect functional short-term and long-term outcomes after RTx. The standardized protocols and operationalized processes applied in RTx might contribute to this finding and may provide a model for other medical procedures that are performed on weekends to improve efficiency and outcomes. The higher rate of surgical complications after weekend RTx needs further elaboration to fully assess the presence of a weekend effect in RTx.
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Morath C, Zeier M, Süsal C. Increased risk of infection-associated death with incompatible kidney transplantations. Transpl Int 2017; 30:1209-1211. [DOI: 10.1111/tri.12995] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2017] [Accepted: 05/30/2017] [Indexed: 01/11/2023]
Affiliation(s)
- Christian Morath
- Division of Nephrology; University of Heidelberg; Heidelberg Germany
| | - Martin Zeier
- Division of Nephrology; University of Heidelberg; Heidelberg Germany
| | - Caner Süsal
- Department of Transplantation Immunology; Institute of Immunology; University of Heidelberg; Heidelberg Germany
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Histological Analysis in ABO-Compatible and ABO-Incompatible Kidney Transplantation by Performance of 3- and 12-Month Protocol Biopsies. Transplantation 2017; 101:1416-1422. [PMID: 27391195 DOI: 10.1097/tp.0000000000001324] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
BACKGROUND ABO-incompatible (ABO-I) kidney transplantation (KTx) is an established procedure to expand living donor sources. Although graft and patient survival rates are comparable between ABO-compatible (ABO-C) and ABO-I KTx, several studies have suggested that ABO-I KTx is associated with infection. Additionally, the histological findings and incidence of antibody-mediated rejection under desensitization with rituximab and plasmapheresis remain unclear. METHODS We reviewed 327 patients who underwent living-donor KTx without preformed donor-specific antibodies (ABO-C, n = 226; ABO-I, n = 101). Patients who underwent ABO-I KTx received 200 mg/body of rituximab and plasmapheresis, and protocol biopsy (PB) was planned at 3 and 12 months. We compared the PB findings, cumulative incidence of acute rejection in both PBs and indication biopsies, infection, and patient and graft survivals. RESULTS The 3- and 12-month PBs were performed in 85.0% and 79.2% of the patients, respectively. Subclinical acute rejection occurred in 6.9% and 9.9% of patients in the ABO-C and ABO-I groups at 3 months (P = 0.4) and in 12.4% and 10.1% at 12 months, respectively (P = 0.5). The cumulative incidence of acute rejection determined by both PBs and indication biopsies was 20.5% and 19.6%, respectively (P = 0.8). The degrees of microvascular inflammation and interstitial fibrosis/tubular atrophy were comparable. Polyomavirus BK nephropathy was found in 2.7% and 3.0% of patients in the ABO-C and ABO-I groups, respectively (P = 1.0). The incidence of other infections and the graft/patient survival rates were not different. CONCLUSIONS Analyses using 3- and 12-month PBs suggested comparable allograft pathology between ABO-C and ABO-I KTx under desensitization with low-dose rituximab and plasmapheresis.
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Okada M, Watarai Y, Iwasaki K, Murotani K, Futamura K, Yamamoto T, Hiramitsu T, Tsujita M, Goto N, Narumi S, Takeda A, Morozumi K, Uchida K, Kobayashi T. Favorable results in ABO-incompatible renal transplantation without B cell-targeted therapy: Advantages and disadvantages of rituximab pretreatment. Clin Transplant 2017; 31. [PMID: 28792635 DOI: 10.1111/ctr.13071] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/02/2017] [Indexed: 12/17/2022]
Abstract
The effectiveness of desensitization with rituximab in ABO-incompatible renal transplantation (ABO-I) has been widely reported. However, ABO-I outcomes are still worse than those of ABO-identical or ABO-compatible renal transplantation (ABO-Id/C). We retrospectively examined the outcomes in consecutive living donor ABO-Id/C (n = 412) and ABO-I (n = 205) cases to elucidate the causes of inferiority in ABO-I. ABO-I cases included recipients treated with rituximab (RIT, n = 131), splenectomy (SPX, n = 21), or neither because of low anti-A/B antibody titers (NoR/S, n = 53). Graft survival, infection, and de novo HLA antibody production were compared for ABO-I and ABO-Id/C, followed by stratification into RIT and NoR/S groups. Propensity score-based methods were employed to limit selection bias and potential confounders. Overall graft survival for ABO-I was significantly lower than that for ABO-Id/C (92.8% vs 97.2% after 5 years, P = .0037). Graft loss due to infection with ABO-I was significantly more frequent than that with ABO-Id/C, whereas acute antibody-mediated rejection (AMR) caused no graft failure in ABO-I recipients. Stratified analysis demonstrated significantly higher infection risk with RIT than with NoR/S. Safe reduction or avoidance of rituximab in desensitization protocols might contribute to further improvement of ABO-I outcome.
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Affiliation(s)
- Manabu Okada
- Department of Transplant and Endocrine Surgery, Nagoya Daini Red Cross Hospital, Nagoya, Japan.,Department of Renal Transplant Surgery, Aichi Medical University School of Medicine, Nagakute, Japan
| | - Yoshihiko Watarai
- Department of Transplant and Endocrine Surgery, Nagoya Daini Red Cross Hospital, Nagoya, Japan
| | - Kenta Iwasaki
- Department of Kidney Disease and Transplant Immunology, Aichi Medical University School of Medicine, Nagakute, Japan
| | - Kenta Murotani
- Division of Biostatistics, Clinical Research Center, Aichi Medical University Hospital, Nagakute, Japan
| | - Kenta Futamura
- Department of Transplant and Endocrine Surgery, Nagoya Daini Red Cross Hospital, Nagoya, Japan
| | - Takayuki Yamamoto
- Department of Transplant and Endocrine Surgery, Nagoya Daini Red Cross Hospital, Nagoya, Japan
| | - Takahisa Hiramitsu
- Department of Transplant and Endocrine Surgery, Nagoya Daini Red Cross Hospital, Nagoya, Japan
| | - Makoto Tsujita
- Department of Transplant and Endocrine Surgery, Nagoya Daini Red Cross Hospital, Nagoya, Japan
| | - Norihiko Goto
- Department of Transplant and Endocrine Surgery, Nagoya Daini Red Cross Hospital, Nagoya, Japan
| | - Shunji Narumi
- Department of Transplant and Endocrine Surgery, Nagoya Daini Red Cross Hospital, Nagoya, Japan
| | - Asami Takeda
- Department of Nephrology, Nagoya Daini Red Cross Hospital, Nagoya, Japan
| | - Kunio Morozumi
- Department of Nephrology, Masuko Memorial Hospital, Nagoya, Japan
| | - Kazuharu Uchida
- Department of Renal Transplant Surgery, Aichi Medical University School of Medicine, Nagakute, Japan.,Department of Kidney Disease and Transplant Immunology, Aichi Medical University School of Medicine, Nagakute, Japan
| | - Takaaki Kobayashi
- Department of Renal Transplant Surgery, Aichi Medical University School of Medicine, Nagakute, Japan
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Gupta KL. Mucormycosis and Cytomegalovirus Co-infection in Renal Transplant Recipients. Indian J Nephrol 2017; 27:245-246. [PMID: 28761224 PMCID: PMC5514818 DOI: 10.4103/0971-4065.175977] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Affiliation(s)
- K L Gupta
- Department of Nephrology, PGIMER, Chandigarh, India
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Abdulrahman Z, Bennani Naciri H, Allal A, Sallusto F, Debiol B, Esposito L, Guilbeau-Frugier C, Kamar N, Rostaing L. Long-term outcomes after ABO-incompatible kidney transplantation; a single-center French study. J Nephropathol 2017. [DOI: 10.15171/jnp.2017.48] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
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Das LK, Ide K, Tanaka A, Morimoto H, Shimizu S, Tanimine N, Tanaka Y, Ohdan H. Fc-gamma receptor 3A polymorphism predicts the incidence of urinary tract infection in kidney-transplant recipients. Hum Immunol 2017; 78:357-362. [DOI: 10.1016/j.humimm.2017.03.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2017] [Revised: 03/11/2017] [Accepted: 03/13/2017] [Indexed: 02/04/2023]
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Yu JH, Chung BH, Yang CW. Impact of ABO incompatible kidney transplantation on living donor transplantation. PLoS One 2017; 12:e0173878. [PMID: 28323892 PMCID: PMC5360260 DOI: 10.1371/journal.pone.0173878] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2016] [Accepted: 02/28/2017] [Indexed: 01/28/2023] Open
Abstract
Background ABO incompatible kidney transplantation (ABOi-KT) is an important approach for overcoming donor shortages. We evaluated the effect of ABOi-KT on living donor KT. Methods Two nationwide transplantation databases were used. We evaluated the impact of ABOi-KT on overall living donor transplant activity and spousal donation as subgroup analysis. In addition, we compared the clinical outcome between ABOi-KT and ABO compatible KT (ABOc-KT) from spousal donor, and performed a Cox proportional hazards regression analysis to define the risk factors affecting the allograft outcomes. Result The introduction of ABOi-KT increased overall living donor KT by 12.2% and its portion was increased from 0.3% to 21.7% during study period. The ABOi-KT in living unrelated KT was two times higher than that of living related donor KT (17.8 vs.9.8%). Spousal donor was a major portion of living unrelated KT (77.6%) and ABOi-KT increased spousal donation from 10% to 31.5% in living donor KT. In addition, increasing rate ABOi-KT from spousal donor was 10 times higher than that of living related donor. The clinical outcome (incidence of acute rejection, allograft function, and allograft and patient survival rates) of ABOi-KT from spousal donor was comparable to that of ABOc-KT. Neither ABO incompatibility nor spousal donor was associated with acute rejection or allograft failure on multivariate analysis. Conclusions ABOi-KT increased overall living donor KT, and ABOi-KT from spousal donor is rapidly increasing with favorable clinical outcomes.
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Affiliation(s)
- Ji Hyun Yu
- Transplantation research center, Division of Nephrology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Byung Ha Chung
- Transplantation research center, Division of Nephrology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Chul Woo Yang
- Transplantation research center, Division of Nephrology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- * E-mail:
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Morath C, Zeier M, Döhler B, Opelz G, Süsal C. ABO-Incompatible Kidney Transplantation. Front Immunol 2017; 8:234. [PMID: 28321223 PMCID: PMC5338156 DOI: 10.3389/fimmu.2017.00234] [Citation(s) in RCA: 65] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2016] [Accepted: 02/17/2017] [Indexed: 12/22/2022] Open
Abstract
ABO-incompatible (ABOi) kidney transplantation has long been considered a contraindication to successful kidney transplantation. During the last 25 years, increasing organ shortage enforced the development of strategies to overcome the ABO antibody barrier. In the meantime, ABOi kidney transplantation has become a routine procedure with death-censored graft survival rates comparable to the rates in compatible transplantations. Desensitization is usually achieved by apheresis and B cell-depleting therapies that are accompanied by powerful immunosuppression. Anti-A/B antibodies are aimed to be below a certain threshold at the time of ABOi kidney transplantation and during the first 2 weeks after surgery. Thereafter, even a rebound of anti-A/B antibodies does not appear to harm the kidney transplant, a phenomenon that is called accommodation, but is poorly understood. There is still concern, however, that infectious complications such as viral disease, Pneumocystis jirovecii pneumonia, and severe urinary tract infections are increased after ABOi transplantations. Recent data from the Collaborative Transplant Study show that during the first year after kidney transplantation, one additional patient death from an infectious complication occurs in 100 ABOi kidney transplant recipients. Herein, we review the recent evidence on ABOi kidney transplantation with a focus on desensitization strategies and respective outcomes.
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Affiliation(s)
- Christian Morath
- Department of Nephrology, University of Heidelberg , Heidelberg , Germany
| | - Martin Zeier
- Department of Nephrology, University of Heidelberg , Heidelberg , Germany
| | - Bernd Döhler
- Transplantation Immunology, Institute of Immunology, University of Heidelberg , Heidelberg , Germany
| | - Gerhard Opelz
- Transplantation Immunology, Institute of Immunology, University of Heidelberg , Heidelberg , Germany
| | - Caner Süsal
- Transplantation Immunology, Institute of Immunology, University of Heidelberg , Heidelberg , Germany
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