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Guo YP, Bao LX, Wang YY, Wen Q, Hang G, Chen B. Literature study on traditional Chinese medicine syndromes after renal transplantation. World J Transplant 2025; 15:96870. [DOI: 10.5500/wjt.v15.i1.96870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Revised: 10/02/2024] [Accepted: 11/12/2024] [Indexed: 11/26/2024] Open
Abstract
BACKGROUND Kidney transplantation is the most effective means to treat patients with renal failure, but its postoperative problems such as rejection reactions, immunosuppressant poisoning, chronic transplant kidney nephropathy, etc. still have not been effectively solved. This study searched for literature on traditional Chinese medicine (TCM) syndromes after kidney transplantation in China, conducted statistical analysis of the results, and sought to identify the underlying patterns.
AIM To understand the TCM syndromes after renal transplantation and associated rules and provide a theoretical basis for further clinical research.
METHODS The literature pertaining to TCM syndromes in renal transplantation, published in the China National Knowledge Infrastructure, Wanfang database, and WIP database from 1970 to 2021, was meticulously searched and comprehensively and statistically analyzed.
RESULTS Following the established inclusion and exclusion criteria, 13 studies were selected for analysis. Post-renal transplantation, no significant discrepancy was noted among the groups based on the location of TCM viscera. However, when categorized according to TCM pathogenic factors, the groups with spleen and kidney yang deficiency, as well as liver and kidney yin deficiency, exhibited a statistically significant difference in the frequency.
CONCLUSION Currently, the research on TCM syndromes pertaining to renal transplantation is in its nascent phase. It is imperative to conduct a multicentric, large-scale survey of TCM syndromes subsequent to renal transplantation in the ensuing years.
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Affiliation(s)
- Yun-Peng Guo
- Tongliao Clinical Medical College, Inner Mongolia Medical University, Tongliao 028000, Inner Mongolia Autonomous Region, China
| | - Ling-Xue Bao
- Department of Urology, Tongliao People's Hospital, Tongliao 028000, Inner Mongolia Autonomous Region, China
| | - Yu-Yang Wang
- Tongliao Clinical Medical College, Inner Mongolia Medical University, Tongliao 028000, Inner Mongolia Autonomous Region, China
| | - Quan Wen
- Department of Urology, Tongliao People's Hospital, Tongliao 028000, Inner Mongolia Autonomous Region, China
| | - Gai Hang
- Department of Urology, Tongliao People's Hospital, Tongliao 028000, Inner Mongolia Autonomous Region, China
| | - Bo Chen
- Department of Urology, Tongliao People's Hospital, Tongliao 028000, Inner Mongolia Autonomous Region, China
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Nakazawa D. Targeting complement in kidney transplantation: Therapeutic approaches based on preclinical and experimental evidence. Transplant Rev (Orlando) 2025; 39:100887. [PMID: 39612603 DOI: 10.1016/j.trre.2024.100887] [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: 08/14/2024] [Revised: 10/14/2024] [Accepted: 11/12/2024] [Indexed: 12/01/2024]
Abstract
The complement system is implicated in various facets of kidney transplantation, including ischemia-reperfusion injury (IRI), delayed graft function, allograft rejection, and chronic allograft injury. IRI, prevalent in cadaveric renal transplantation, leads to acute tubular necrosis and engages innate immunity, including neutrophils and the complement system, fostering a cycle of inflammation and necrosis. Experimental and preclinical evidence suggest that targeting the complement system could offer therapeutic benefits in IRI during kidney transplantation. This article explores potential therapeutic approaches targeting complement pathways in kidney transplantation, drawing from experimental and preclinical research findings.
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Affiliation(s)
- Daigo Nakazawa
- Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
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Hanouneh T, Attieh RM, Craver E, Jebrini A, Elrefaei M, Jarmi T. Comparative analysis of Basiliximab and Alemtuzumab induction therapies in blood type A2-to-B kidney transplantation: Impact on kidney function and de novo donor-specific HLA antibodies. Transpl Immunol 2023; 81:101958. [PMID: 37949378 DOI: 10.1016/j.trim.2023.101958] [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: 07/28/2023] [Revised: 11/07/2023] [Accepted: 11/07/2023] [Indexed: 11/12/2023]
Abstract
PURPOSE Blood group B kidney transplant candidates have lower transplantation rates and longer waiting times compared to other blood groups. Kidney transplantation from blood group A2-to-B has offered a solution for these patients. This study aimed to investigate the impact of Basiliximab and Alemtuzumab induction therapies on kidney function and de novo donor-specific antibodies (DSA) in blood type A2-to-B kidney transplant recipients within the first 12 months of post-transplant. METHODS A retrospective analysis was conducted on 110 consecutive A2-to-B kidney transplant recipients between January 2015 and December 2022. Of these, 46 (41.8%) received Basiliximab, while 64 (58.2%) received Alemtuzumab as induction therapy. Demographics and comorbidities data were collected and compared between the two groups. Serum samples collected at 4- and 12-month intervals post-transplant were used to assess the presence of de novo DSA. Kidney allograft function was evaluated by monitoring serum creatinine levels and assessing Creatinine Clearance based on 24-h urine collection at various time points. RESULTS During the follow-up period, 20.00% of patients who received Alemtuzumab developed de novo DSA, whereas none of the patients induced with Basiliximab developed de novo DSA (p = 0.038). Recipients who received Basiliximab were older (mean age = 72.00) and received higher Kidney Donor Profile Index (KDPI) kidneys (mean = 75) compared to those induced with Alemtuzumab (mean age = 58.00, mean KDPI = 49) (p < 0.001), with no significant difference observed in the last follow-up creatinine clearance or creatinine levels between the two groups (p = 0.28). CONCLUSION The use of Basiliximab as induction immunosuppression in A2-to-B kidney transplant recipients is associated with a lower incidence of de novo HLA DSA formation without significant differences in overall renal function compared to Alemtuzumab.
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Affiliation(s)
- Tareq Hanouneh
- Department of Transplant, Mayo Clinic, Jacksonville, FL, United States of America.
| | - Rose Mary Attieh
- Department of Transplant, Mayo Clinic, Jacksonville, FL, United States of America.
| | - Emily Craver
- Department of Biostatistics, Mayo Clinic, Jacksonville, FL, United States of America.
| | - Abdullah Jebrini
- Department of Transplant, Mayo Clinic, Jacksonville, FL, United States of America.
| | - Mohamed Elrefaei
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, FL, United States of America.
| | - Tambi Jarmi
- Department of Transplant, Mayo Clinic, Jacksonville, FL, United States of America.
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Sato T, Azuma Y, Ozone C, Okazaki M, Takeda A, Okada M, Futamura K, Hiramitsu T, Goto N, Narumi S, Watarai Y. Possible Advantage of Glucagon-Like Peptide 1 Receptor Agonists for Kidney Transplant Recipients With Type 2 Diabetes. J Clin Endocrinol Metab 2023; 108:2597-2603. [PMID: 36974363 DOI: 10.1210/clinem/dgad177] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Revised: 03/19/2023] [Accepted: 03/24/2023] [Indexed: 03/29/2023]
Abstract
CONTEXT Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) have the potential to improve native kidney function. OBJECTIVE This work aimed to elucidate the possible protective effects of GLP-1 RAs on kidney graft function after successful kidney transplantation (KTX). METHODS This retrospective cohort study included all KTX recipients (KTRs) at our facility with type 2 diabetes who were followed up from 1 month post-transplantation for 24 months or longer as of December 31, 2020. We investigated associations between the use of GLP-1 RAs and other antidiabetic medications (non-GLP-1 RAs) and the risk of sustained estimated glomerular filtration rate (eGFR) reduction (40% reduction compared with baseline for 4 months) for KTRs with type 2 diabetes. We calculated the propensity score of initiating GLP-1 RAs compared with that of initiating non-GLP-1 RAs as a function of baseline covariates using logistic regression. The inverse probability of the treatment-weighted odds ratio was estimated to control for baseline confounding variables. Sodium-glucose cotransporter 2 inhibitor use was a competing event. The primary outcome was sustained eGFR reduction of at least 40% from baseline for 4 months post-transplantation. RESULTS Seventy-three patients were GLP-1 RA users and 73 were non-GLP-1 RA users. Six patients and 1 patient in the non-GLP-1 RA and GLP-1 RA groups had sustained eGFR reduction. GLP-1 RA use after KTX was associated with a lower risk of sustained eGFR reduction. CONCLUSION GLP-1 RAs resulted in lower eGFR reduction compared with non-GLP-1 RAs and may contribute to better kidney graft survival after KTX.
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Affiliation(s)
- Tetsuhiko Sato
- Division of Integrated Strategic Medicine, Japanese Red Cross Aichi Medical Center, Nagoya Daini Hospital, Nagoya, Aichi 4668650, Japan
- Division of Diabetes and Endocrinology, Japanese Red Cross Aichi Medical Center, Nagoya Daini Hospital, Nagoya, Aichi 4668650, Japan
| | - Yoshinori Azuma
- Division of Diabetes and Endocrinology, Japanese Red Cross Aichi Medical Center, Nagoya Daini Hospital, Nagoya, Aichi 4668650, Japan
| | - Chikafumi Ozone
- Division of Diabetes and Endocrinology, Japanese Red Cross Aichi Medical Center, Nagoya Daini Hospital, Nagoya, Aichi 4668650, Japan
| | - Mikako Okazaki
- Division of Diabetes and Endocrinology, Japanese Red Cross Aichi Medical Center, Nagoya Daini Hospital, Nagoya, Aichi 4668650, Japan
| | - Asami Takeda
- Department of Nephrology, Japanese Red Cross Aichi Medical Center, Nagoya Daini Hospital, Nagoya, Aichi 4668650, Japan
| | - Manabu Okada
- Department of Transplant Surgery, Japanese Red Cross Aichi Medical Center, Nagoya Daini Hospital, Nagoya, Aichi 4668650, Japan
| | - Kenta Futamura
- Department of Transplant Nephrology, Japanese Red Cross Aichi Medical Center, Nagoya Daini Hospital, Nagoya, Aichi 4668650, Japan
| | - Takahisa Hiramitsu
- Department of Transplant Surgery, Japanese Red Cross Aichi Medical Center, Nagoya Daini Hospital, Nagoya, Aichi 4668650, Japan
| | - Norihiko Goto
- Department of Transplant Nephrology, Japanese Red Cross Aichi Medical Center, Nagoya Daini Hospital, Nagoya, Aichi 4668650, Japan
| | - Shunji Narumi
- Department of Transplant Surgery, Japanese Red Cross Aichi Medical Center, Nagoya Daini Hospital, Nagoya, Aichi 4668650, Japan
| | - Yoshihiko Watarai
- Department of Transplant Surgery, Japanese Red Cross Aichi Medical Center, Nagoya Daini Hospital, Nagoya, Aichi 4668650, Japan
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Kang ZY, Ma S, Liu W, Liu C. Effect of blood transfusion post kidney transplantation on de novo human leukocytes antigen donor-specific antibody development and clinical outcomes in kidney transplant recipients: A systematic review and meta-analysis. Transpl Immunol 2023; 78:101801. [PMID: 36841513 DOI: 10.1016/j.trim.2023.101801] [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: 10/04/2022] [Revised: 01/10/2023] [Accepted: 02/21/2023] [Indexed: 02/27/2023]
Abstract
The relationship between blood transfusion following kidney transplantation (KT) and the development of de novo donor-specific antibodies (dnDSA) is controversial. This was investigated by conducting a meta-analysis of studies on patients who underwent KT with or without blood transfusion, and by evaluating the effect of post-KT blood transfusion on clinical outcomes of kidney transplant recipients. Relevant studies in the PubMed, EMBASE, and Cochrane Library databases were identified from inception to July 1, 2022. Two reviewers independently extracted data from the selected articles and estimated study quality. A fixed effects or random effects model was used to pool data according to the heterogeneity among studies. Data included in the meta-analysis were derived from 11 studies with a total of 19,543 patients including 6191 with and 13,352 without blood transfusion post-KT. We assessed the pooled associations between blood transfusion and occurrence of dnDSA and clinical outcomes of transplant recipients. Blood transfusion was strongly correlated with the development of dnDSA (relative risk [RR] = 1.40, 95% confidence interval [CI]: 1.17-1.67; P < 0.05). Patients with blood transfusion had a higher risk of developing anti-human leukocyte antigen (HLA) class I dnDSA than non-transfused patients (RR = 1.75, 95% CI: 1.14-2.69; P < 0.05) as well as significantly higher rates of antibody-mediated rejection (AMR) (RR = 1.41, 95% CI: 1.21-2.35; P < 0.05) and graft loss (RR = 1.75, 95% CI: 1.30-2.35; P < 0.05). There were no statistically significant differences between the two groups in the development of anti-HLA antibodies, anti-HLA class II dnDSA, and anti-HLA class I and II dnDSA; delayed graft function; T cell-mediated rejection; acute rejection; borderline rejection; or patient death. Our results suggest that blood transfusion was associated with dnDSA development in KT recipients. The findings of this systematic review also suggest that post-KT blood transfusion recipients have a higher risk of AMR, and graft loss compared with non-transfused patients. Evidence from this meta-analysis indicates that the use of blood transfusion post-KT is associated with a significantly higher risk of immunological sensitization. More and higher quality results from large randomized controlled trials are still needed to inform clinical practice.
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Affiliation(s)
- Zhong-Yu Kang
- Department of Blood Transfusion, Tianjin First Central Hospital, School of Medicine, NanKai University, Tianjin, Nankai, China
| | - Shuangshuang Ma
- Department of Blood Transfusion, Tianjin First Central Hospital, School of Medicine, NanKai University, Tianjin, Nankai, China
| | - Wei Liu
- Department of Blood Transfusion, Tianjin First Central Hospital, School of Medicine, NanKai University, Tianjin, Nankai, China
| | - Chun Liu
- Department of Blood Transfusion, Tianjin First Central Hospital, School of Medicine, NanKai University, Tianjin, Nankai, China.
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De Novo Membranous Nephropathy Associated With Antibody-Mediated Rejection in Kidney Transplant Recipients. Transplant Proc 2022; 54:1270-1277. [DOI: 10.1016/j.transproceed.2021.11.041] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2021] [Accepted: 11/19/2021] [Indexed: 01/11/2023]
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Nowańska K, Wiśnicki K, Kuriata-Kordek M, Krajewska M, Banasik M. The role of endothelin II type A receptor (ETAR) in transplant injury. Transpl Immunol 2021; 70:101505. [PMID: 34793957 DOI: 10.1016/j.trim.2021.101505] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Revised: 11/11/2021] [Accepted: 11/11/2021] [Indexed: 12/15/2022]
Abstract
PURPOSE OF REVIEW Antibody-mediated rejection is the leading cause of deterioration of graft function and graft loss after kidney transplantation. Recent studies have reported an increasing role of non-HLA antibodies in the humoral injury after kidney transplantation. We decided to present the influence of non-HLA antibodies - anti-endothelin II type A receptor (ETAR) on a transplanted kidney and characterize the significance of their receptor. RECENT FINDINGS The role of non-HLA antibodies is still uncertain. Many studies suggest that the presence of non-HLA antibodies, including anti-ETAR antibodies, is among the risk factors for antibody-mediated rejection, graft injury, and graft loss. The discovery of new antigen targets and antibodies, which participate in the humoral response, has provided a significantly better understanding of the mechanism of antibody-mediated rejection after organ transplantation. SUMMARY Endothelin and its receptors play an important role in physiology and pathophysiology after solid organ transplantation. ETAR and antibodies against ETAR may participate in humoral rejection and graft damage. The measurement of anti-ETAR antibodies may identify patients with an increased risk of rejection and even loss of a transplanted organ. Expression of ETAR detected in biopsy of transplant could become an additional tool used to better understand humoral activity. More research is needed to address many questions about non-HLA directed rejection and graft damage.
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Affiliation(s)
- Katarzyna Nowańska
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wrocław, Poland
| | - Krzysztof Wiśnicki
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wrocław, Poland
| | - Magdalena Kuriata-Kordek
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wrocław, Poland
| | - Magdalena Krajewska
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wrocław, Poland
| | - Mirosław Banasik
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wrocław, Poland.
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8
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Wang J, Li X, Wu X, Wang Z, Zhang C, Cao G, Liu S, Yan T. Gut microbiota alterations associated with antibody-mediated rejection after kidney transplantation. Appl Microbiol Biotechnol 2021; 105:2473-2484. [PMID: 33625548 DOI: 10.1007/s00253-020-11069-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2020] [Revised: 12/02/2020] [Accepted: 12/17/2020] [Indexed: 12/13/2022]
Abstract
Antibody-mediated rejection (AMR) has become the major challenge for kidney transplantation, and the efficacy of existing therapies was limited to prevent AMR. Increasing evidences have demonstrated the link between gut microbiota alterations and allograft outcome. However, there has been no comprehensive analysis to profile the gut microbiota associated with AMR after kidney transplantation. We performed this study to characterize the gut microbiota possibly associated with AMR. Fecal specimens were collected from 24 kidney transplantation recipients with AMR and 29 controls. DNA extracted from the specimens was processed for 16S rRNA gene sequencing using Illumina MiSeq. Gut microbial community of recipients with AMR was significantly different from that of controls based on unweighted (P = 0.001) and weighted (P = 0.02) UniFrac distances, and the bacterial richness (observed species: P = 0.0448; Chao1 index: P = 0.0450; ACE index: P = 0.0331) significantly decreased in the AMR group. LEfSe showed that 1 phylum, 5 classes, 7 families, and 10 genera were increased, whereas 1 class, 2 order, 3 families, and 4 genera were decreased in the AMR group. Specific taxa such as Clostridiales could be potentially used as biomarkers to distinguish the recipients with AMR from the controls (AUC = 0.77). PICRUSt analysis illustrated that 16 functional pathways were with significantly different abundances in the AMR and control groups. Our findings provide a foundation for further investigation on the role of gut microbiota in AMR after kidney transplantation, and potentially support novel diagnostic biomarkers and therapeutic options for AMR. KEY POINTS: • Gut microbial community of kidney recipients with AMR was different from that of controls. • Clostridiales is a potential marker to distinguish recipients with AMR from controls.
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Affiliation(s)
- Junpeng Wang
- Department of Urology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, 450003, China.,Department of Organ Transplantation, Zhujiang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Xin Li
- Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou, 450001, China.,Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, China
| | - Xiaoqiang Wu
- Department of Urology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, 450003, China
| | - Zhiwei Wang
- Department of Urology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, 450003, China
| | - Chan Zhang
- Department of Urology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, 450003, China
| | - Guanghui Cao
- Department of Urology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, 450003, China
| | - Shun Liu
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, China
| | - Tianzhong Yan
- Department of Urology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, 450003, China.
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Arai T, Oguchi H, Shinoda K, Sakurabayashi K, Mikami T, Itabashi Y, Sakai K. Clinicopathological Analysis of Acute/Active Antibody-Mediated Rejection in Renal Allografts According to the Banff 2013 Classification. Nephron Clin Pract 2020; 144 Suppl 1:18-27. [PMID: 33264791 DOI: 10.1159/000512143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Accepted: 10/08/2020] [Indexed: 11/19/2022] Open
Abstract
AIM This study evaluated the clinicopathological findings of acute/active antibody-mediated rejection (AABMR) according to the Banff 2013 classification. METHODS We analyzed 345 biopsies of 269 kidney transplant recipients. Pathological AABMR (PAABMR) was defined as histological evidence of acute tissue injury and endothelial injury by light microscopy regardless of donor-specific antibodies (DSAs). RESULTS Among the 345 biopsies, 29 (8.4%) were diagnosed as PAABMR. The mean g score was 1.17 ± 0.60, the mean ptc score was 1.97 ± 1.32, and DSA positivity was found in 69% of PAABMR. The mean duration after transplantation was 22.9 ± 26.7 months. Among 3 groups (DSA-high, mean fluorescence intensity (MFI) ≥ 5,000; DSA-low, MFI < 5,000 to ≥1,000; below cutoff), ABO incompatibility in DSA-high was significantly lower and second transplantation in DSA-high was significantly higher. We found 83% of PAABMR by the protocol biopsy (subclinical AABMR [SAABMR]). The short-term clinical and light microscopical changes in 8 cases of SAABMR did not show worsening during follow-up period (9-24 months). However, ultrastructural finding, including glomerular endothelial swelling, subendothelial electron-lucent widening, and early glomerular basement duplication, were found by electron microscopy (EM) in the first biopsies, and half of the SAABMR cases developed de novo circular peritubular capillary multilayering in the follow-up biopsies. CONCLUSION PAABMR was mainly found by the protocol biopsy. The short-term follow-up of SAABMR patients did not show worsening clinically and light microscopically, but ultrastructural examination by EM was useful to detect early lesions of endothelial injury and progression of glomerular and peritubular capillary basement membrane alterations.
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Affiliation(s)
- Taichi Arai
- Department of Nephrology, Toho University Faculty of Medicine, Tokyo, Japan
| | - Hideyo Oguchi
- Department of Nephrology, Toho University Faculty of Medicine, Tokyo, Japan,
| | - Kazunobu Shinoda
- Department of Nephrology, Toho University Faculty of Medicine, Tokyo, Japan
| | - Kei Sakurabayashi
- Department of Nephrology, Toho University Faculty of Medicine, Tokyo, Japan
| | - Tetuo Mikami
- Department of Pathology, Toho University Faculty of Medicine, Tokyo, Japan
| | - Yoshihiro Itabashi
- Department of Nephrology, Toho University Faculty of Medicine, Tokyo, Japan
| | - Ken Sakai
- Department of Nephrology, Toho University Faculty of Medicine, Tokyo, Japan
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10
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Tsivilika M, Doumaki E, Stavrou G, Sioga A, Grosomanidis V, Meditskou S, Maranginos A, Tsivilika D, Stafylarakis D, Kotzampassi K, Papamitsou T. The adaptive immune response in cardiac arrest resuscitation induced ischemia reperfusion renal injury. ACTA ACUST UNITED AC 2020; 27:15. [PMID: 33014901 PMCID: PMC7526263 DOI: 10.1186/s40709-020-00125-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Accepted: 09/23/2020] [Indexed: 02/07/2023]
Abstract
Background The present study aims to investigate, immunohistochemically, the role of the adaptive immune response in cardiac arrest/resuscitation-induced ischemia–reperfusion renal injury (IRI), namely to assess the presence of lymphocytes in renal tissue samples and the connection between the extent of the damage and the concentration of the lymphocytes by comparing the kidneys of non resuscitated swine with the kidneys of resuscitated swine. Methods Twenty four swine underwent cardiac arrest (CA) via a pacemaker wire. After 7 min, without any intervention, Cardiopulmonary Resuscitation, CPR, was commenced. Five min after CPR was commenced advanced life-support, ALS. Animals were divided into resuscitated animals and non resuscitated animals. Tissue samples obtained from the two groups for immunohistological study aiming to detect T-cells, B-cells and plasma cells using CD3 + , CD20 + , and CD138 + antibodies. Results There seems to be a strong concentration of T lymphocytes in the kidney tissues after ischemia of both non-resuscitated and resuscitated swine. B lymphocytes, also, appear to have infiltrated the ischemic kidneys of both animal groups; nevertheless, the contribution of T lymphocytes to the induction of injury remains greater. There is no strong evidence of correlation between the plasma cells and the damage. Conclusion The adaptive immune response seems to have a strong association with kidney injury and acute tubular necrosis after cardiac arrest/ resuscitation-induced ischemia–reperfusion. However, the extent to which the adaptive immune cells are involved in the induction of renal injury remains uncertain and there are many questions about the mechanism of function of these cells, the answers of which require further studies.
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Affiliation(s)
- Maria Tsivilika
- Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Gianni Chalkidi 45, Charilaou, 54249 Thessaloniki, Greece
| | - Eleni Doumaki
- 1st Department of Internal Medicine, Faculty of Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - George Stavrou
- Department of Surgery, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.,Department of Colorectal Surgery, Addenbrooke's Hospital, Cambridge, UK
| | - Antonia Sioga
- Laboratory of Histology- Embryology, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Vasilis Grosomanidis
- Department of Surgery, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Soultana Meditskou
- Laboratory of Histology- Embryology, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | | | | | - Dimitrios Stafylarakis
- 2nd Department of Urology of Aristotle University of Thessaloniki, Papageorgiou General Hospital, Thessaloniki, Greece
| | - Katerina Kotzampassi
- Department of Surgery, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Theodora Papamitsou
- Laboratory of Histology- Embryology, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
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11
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Fukuoka K, Tokodai K, Miyagi S, Nakanishi W, Nishimura R, Fujio A, Watanabe H, Taniuchi S, Naitoh T, Ishida T, Unno M, Kamei T. Chronic Active Antibody-Mediated Rejection With Donor-Specific Anti-HLA-DP Antibodies Following Living Donor Kidney Transplantation: A Case Report. Transplant Proc 2020; 52:1937-1939. [PMID: 32586663 DOI: 10.1016/j.transproceed.2020.02.130] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2019] [Revised: 02/11/2020] [Accepted: 02/22/2020] [Indexed: 11/25/2022]
Abstract
Posttransplant donor-specific anti-HLA antibodies (DSA) cause chronic antibody-mediated rejection. Anti-DR and anti-DQ DSAs have especially been shown to be associated with negative graft function. In contrast, the prevalence and significance of anti-DP DSA have not been well established and remain unclear. We report a case of living donor kidney transplantation. The level of serum creatinine gradually became elevated because of chronic active antibody-mediated rejection, which was considered to be caused by anti-DP DSA. In this report, we indicate the significance of pretransplant screening for HLA-DP in donors to evaluate more comprehensively the donor specificity of posttransplant HLA antibodies.
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Affiliation(s)
- Kengo Fukuoka
- Department of Surgery, Tohoku University Hospital, Sendai, Miyagi, Japan.
| | - Kazuaki Tokodai
- Department of Surgery, Tohoku University Hospital, Sendai, Miyagi, Japan
| | - Shigehito Miyagi
- Department of Surgery, Tohoku University Hospital, Sendai, Miyagi, Japan
| | - Wataru Nakanishi
- Department of Surgery, Tohoku University Hospital, Sendai, Miyagi, Japan
| | - Ryuichi Nishimura
- Department of Surgery, Tohoku University Hospital, Sendai, Miyagi, Japan
| | - Atsushi Fujio
- Department of Surgery, Tohoku University Hospital, Sendai, Miyagi, Japan
| | - Hirofumi Watanabe
- Department of Pathology, Tohoku University Hospital, Sendai, Miyagi, Japan
| | - Shinji Taniuchi
- Department of Pathology, Osaki Citizen Hospital, Osaki, Miyagi, Japan
| | - Takeshi Naitoh
- Department of Surgery, Tohoku University Hospital, Sendai, Miyagi, Japan
| | - Takanori Ishida
- Department of Surgery, Tohoku University Hospital, Sendai, Miyagi, Japan
| | - Michiaki Unno
- Department of Surgery, Tohoku University Hospital, Sendai, Miyagi, Japan
| | - Takashi Kamei
- Department of Surgery, Tohoku University Hospital, Sendai, Miyagi, Japan
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12
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Kolonko A, Słabiak-Błaż N, Karkoszka H, Więcek A, Piecha G. The Preliminary Results of Bortezomib Used as A Primary Treatment for An Early Acute Antibody-Mediated Rejection after Kidney Transplantation-A Single-Center Case Series. J Clin Med 2020; 9:jcm9020529. [PMID: 32075220 PMCID: PMC7074248 DOI: 10.3390/jcm9020529] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 02/06/2020] [Accepted: 02/12/2020] [Indexed: 01/10/2023] Open
Abstract
Proteasome inhibitor bortezomib has been used in the treatment of refractory cases of acute and chronic antibody-mediated rejection (AMR) in kidney transplant recipients. However, its efficacy and safety as a primary treatment for early AMR has been scarcely investigated. We herein present our preliminary experience with bortezomib- and plasmapheresis-based primary treatment for early AMR. Thirteen patients transplanted between October 2015 and September 2019 were treated (starting at median 19th post-transplant day) with bortezomib/plasmapheresis protocol for early biopsy-proven AMR. Twelve out of thirteen patients received 4 doses and one patient recieved 3 doses of bortezomib (1.3 mg/m2 per dose). In 11/13 patients, 4–7 concomitant plasmapheresis sessions were performed, with or without intravenous immunoglobulin (IVIG). Of note, rituximab was not used in all study patients. The kidney graft and patient survival were 100%. The mean 3-month estimated glomerular filtration rate (eGFR) was 55.3 (95%CI: 44.9–65.8) mL/min/1.73m2, 8/13 patients completed 12-month follow-up with mean eGFR 60.4 (45.4–75.4) mL/min/1.73m2, and 6/13 patients completed a 24-month follow-up period with mean eGFR 73.9 (56.7–91.1) mL/min/1.73m2. Neutropenia < 1 G/L was observed in one patient, third or fourth grade thrombocytopenia in two patients, and eleven patients needed a blood transfusion (median: 2 units/patient). The mid-term results of a primary bortezomib-based treatment for kidney AMR showed its non-inferiority as compared to preceding regimens and acceptable safety. However, our data should be validated in a multicenter randomized trial.
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13
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Reusz GS. Urinary proteomics: fancy gadgetry or a clinically useful diagnostic instrument? The end-user's perspective. Transpl Int 2018; 32:25-27. [DOI: 10.1111/tri.13374] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2018] [Accepted: 11/07/2018] [Indexed: 12/31/2022]
Affiliation(s)
- George S. Reusz
- 1st Department of Pediatrics; Semmelweis University; Budapest Hungary
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14
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Doreille A, Dieudé M, Cardinal H. The determinants, biomarkers, and consequences of microvascular injury in kidney transplant recipients. Am J Physiol Renal Physiol 2018; 316:F9-F19. [PMID: 30379097 DOI: 10.1152/ajprenal.00163.2018] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
Independent of the initial cause of kidney disease, microvascular injury to the peritubular capillary network appears to play a central role in the development of interstitial fibrosis in both native and transplanted kidney disease. This association is explained by mechanisms such as the upregulation of profibrotic genes and epigenetic changes induced by hypoxia, capillary leakage, endothelial and pericyte transition to interstitial fibroblasts, as well as modifications in the secretome of endothelial cells. Alloimmune injury due to antibody-mediated rejection and ischemia-reperfusion injury are the two main etiologies of microvascular damage in kidney transplant recipients. The presence of circulating donor-specific anti-human leukocyte antigen (HLA) antibodies, histological findings, such as diffuse C4d staining in peritubular capillaries, and the extent and severity of peritubular capillaritis, are commonly used clinically to provide both diagnostic and prognostic information. Complement-dependent assays, circulating non-HLA antibodies, or evaluation of the microvasculature with novel imaging techniques are the subject of ongoing studies.
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Affiliation(s)
- Alice Doreille
- Research Centre, Centre Hospitalier de l'Université de Montréal , Montreal, Quebec , Canada.,Université Paris-Sud , Paris , France
| | - Mélanie Dieudé
- Research Centre, Centre Hospitalier de l'Université de Montréal , Montreal, Quebec , Canada.,Canadian Donation and Transplantation Research Program, Montreal, Quebec, Canada
| | - Heloise Cardinal
- Research Centre, Centre Hospitalier de l'Université de Montréal , Montreal, Quebec , Canada.,Canadian Donation and Transplantation Research Program, Montreal, Quebec, Canada
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