SP700THE PRESENCE OF ANTI-AT1R ANTIBODIES IN BLOOD AND AT1 RECEPTOR EXPRESSION IN BIOPSY FOR CAUSE OF RENAL TRANSPLANT RECIPIENTS MAY BE ASSOCIATED WITH HIGHER GRAFT LOSS AND MORE ANTIBODY MEDIATED REJECTION CASES

Abstract Background and Aims The manifestation of anti-angiotensin II type 1 receptor (AT1R) antibodies is considered a risk factor for transplant injury, however, the occurrence of AT1-Receptor expression in renal transplant biopsy may be an additional feature which can help to predict transplant loss. The aim of our study was to evaluate the expression of AT1R together with their antibodies and assess the risk of transplant loss in patients who had a renal transplant indication biopsy. Method AT1-Receptor immunoreactivity was analyzed in renal transplant biopsies. Additionally, we analyzed the presence of anti-AT1R antibodies in these patients using ELISA method. The result of more than 10 was assessed as positive. Immunohistochemical evaluation of AT1-Receptor expression was performed on 4 μm-thick paraffin sections mounted on silanized slides. AT1-Receptor expression was analyzed in five compartments: 1.tubular epithelium, 2.glomeruli, 3.peritubular capillaries, 4.interstitium and 5.renal blood vessels (small and intermediate arteries) based on a 3-step scale. Results We checked 156 samples of biopsies for the immunoreactivity of the AT1-Receptor. In all these patients we were able to access the presence of anti-AT1R antibodies. A group of 67 patients had positive AT1-Receptor expression (R+) and 16 patients had positive anti-AT1R antibodies (R+Ab+) results. A group of 89 patients had no expression of AT1-Receptor (R-), among which 51 had also no anti-AT1R (R-Ab-). One-year post-biopsy graft loss in the R+Ab+ patients was 37% (6/16) compared to 10% (7/69) in the R-Ab- patients (p = 0.006). Two-year and three-year graft loss was 43% vs. 17% (p=0.02) and 50% vs. 21% (p=0.02) respectively. Moreover, six patients had positive staining of AT1-Receptors in microcirculation (glomeruli and peritubular capillaries), which was associated with antibody mediated rejection. Conclusion The presence of anti-AT1R antibodies in serum together with the expression of AT1-Receptor in transplant biopsy was associated with a significantly higher graft loss. The relevance of AT1-Receptor expression analyzed together with anti-AT1R antibodies should be considered for better transplant immunological risk assessment.

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Treatment of Chronic Active Antibody-mediated Rejection in Renal Transplant Recipients – A single center retrospective study

10.21203/rs.2.13704/v4 ◽

2019 ◽

Author(s):

Hsien-Fu Chiu ◽

Mei-Chin Wen ◽

Ming-Ju Wu ◽

Cheng-Hsu Chen ◽

Tung-Min Yu ◽

...

Keyword(s):

Renal Transplant ◽

Graft Loss ◽

Rank Test ◽

Renal Transplant Recipients ◽

Supportive Treatment ◽

Aggressive Treatment ◽

Transplant Recipients ◽

Antibody Mediated Rejection ◽

Group 2 ◽

Group 1

Abstract Background: Chronic active antibody-mediated rejection is a major etiology of graft loss in renal transplant recipients. However, there are no approved treatments. Methods: Computerized records from Taichung Veterans General Hospital were collected to identify the renal transplant biopsies performed in the past 7 years with the diagnosis of chronic active antibody-mediated rejection. The patients were divided into two groups according to treatment strategy: Group 1: aggressive treatment (double filtration plasmapheresis and one of the followings: rituximab, intravenous immunoglobulin, antithymogycte globulin, bortezomib, or methylprednisolone pulse therapy); and group 2: supportive treatment. Results: From February 2009 to December 2017, a total of 82 patients with biopsy-proven chronic antibody mediated rejection were identified. Kaplan-Meier analysis of death-censored graft survival showed a worse survival in group 2 ( P = 0.015 by log-rank test). Adverse event-free survival was lower in group 1, whereas patient survival was no significant different. Proteinuria and supportive treatment were independent risk factors for graft loss in multivariate analysis. Conclusions : Aggressive treatment was associated with better graft outcome. However, higher incidence of adverse events merit personalized treatment, especially for those with higher risk of infection. Appropriate prophylactic antibiotics are recommended for aggressive treatment patients.

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Treatment of Chronic Active Antibody-mediated Rejection in Renal Transplant Recipients – A single center retrospective study

10.21203/rs.2.13704/v3 ◽

2019 ◽

Author(s):

Hsien-Fu Chiu ◽

Mei-Chin Wen ◽

Ming-Ju Wu ◽

Cheng-Hsu Chen ◽

Tung-Min Yu ◽

...

Keyword(s):

Renal Transplant ◽

Adverse Events ◽

Graft Loss ◽

Renal Transplant Recipients ◽

Supportive Treatment ◽

Aggressive Treatment ◽

Transplant Recipients ◽

Antibody Mediated Rejection ◽

Group 2 ◽

Group 1

Abstract Background: A plethora of evidences suggest that the most important cause of late graft loss in renal transplant recipients is chronic active antibody-mediated rejection. However, there are no consensus on treatment strategies. Methods: We retrospectively analyzed clinical and pathological data of renal transplant recipients who received kidney graft biopsy with confirmed diagnosis of chronic active antibody-mediated rejection in the past 7 years. The patients were divided into two groups according to treatment strategy: Group 1: aggressive treatment (double filtration plasmapheresis and one of the followings: rituximab, intravenous immunoglobulin, antithymogycte globulin, bortezomib, or methylprednisolone pulse therapy); and group 2: supportive treatment. Results: From February 2009 to December 2017, a total of 82 patients with biopsy-proven chronic antibody mediated rejection were identified. Kaplan-Meier analysis of death-censored graft survival showed a worse survival in group 2 ( P = 0.015 by log-rank test). Adverse event-free survival was lower in group 1, whereas patient survival was no significant different. Proteinuria and supportive treatment were independent risk factors for graft loss in multivariate analysis. Conclusions : Aggressive treatment was associated with better graft outcome. However, higher incidence of adverse events merit personalized treatment, especially for those with higher risk of infection. Appropriate prophylactic antibiotics are recommended for aggressive treatment patients. Key words: chronic active antibody mediated rejection, kidney transplantation, graft survival, adverse events

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Rituximab Does Not Prevent Graft Loss in Renal Transplant Recipients With Chronic Antibody Mediated Rejection With Significant Renal Impairment and Nephrotic Range Proteinuria.

Transplantation Journal ◽

10.1097/00007890-201407151-01590 ◽

2014 ◽

Vol 98 ◽

pp. 477 ◽

Cited By ~ 1

Author(s):

S. Anwar ◽

R. Delos Santos ◽

T. Horwedel ◽

D. Brennan ◽

C. Klein

Keyword(s):

Renal Transplant ◽

Renal Impairment ◽

Graft Loss ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Antibody Mediated Rejection ◽

Nephrotic Range Proteinuria

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Treatment of Chronic Active Antibody-mediated Rejection in Renal Transplant Recipients – A single center retrospective study

10.21203/rs.2.13704/v2 ◽

2019 ◽

Author(s):

Hsien-Fu Chiu(Former Corresponding Author) ◽

Mei-Chin Wen ◽

Ming-Ju Wu ◽

Cheng-Hsu Chen ◽

Tung-Min Yu ◽

...

Keyword(s):

Renal Transplant ◽

Adverse Events ◽

Graft Loss ◽

Renal Transplant Recipients ◽

Supportive Treatment ◽

Aggressive Treatment ◽

Transplant Recipients ◽

Antibody Mediated Rejection ◽

Group 2 ◽

Group 1

Abstract Background: A plethora of evidences suggest that the most important cause of late graft loss in renal transplant recipients is chronic active antibody-mediated rejection. However, there are no consensus on treatment strategies. Methods: We retrospectively analyzed clinical and pathological data of renal transplant recipients who received kidney graft biopsy with confirmed diagnosis of chronic active antibody-mediated rejection in the past 7 years. The patients were divided into two groups according to treatment strategy: Group 1: aggressive treatment (double filtration plasmapheresis and one of the followings: rituximab, intravenous immunoglobulin, antithymogycte globulin, bortezomib, or methylprednisolone pulse therapy); and group 2: supportive treatment. Results: From February 2009 to December 2017, a total of 82 patients with biopsy-proven chronic antibody mediated rejection were identified. Kaplan-Meier analysis of death-censored graft survival showed a worse survival in group 2 (P = 0.015 by log-rank test). Adverse event-free survival was lower in group 1, whereas patient survival was no significant different. Proteinuria and supportive treatment were independent risk factors for graft loss in multivariate analysis. Conclusions: Aggressive treatment was associated with better graft outcome. However, higher incidence of adverse events merit personalized treatment, especially for those with higher risk of infection. Appropriate prophylactic antibiotics are recommended for aggressive treatment patients. Key words: chronic active antibody mediated rejection, kidney transplantation, graft survival, adverse events

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Treatment of Chronic Active Antibody-mediated Rejection in Renal Transplant Recipients – A single center retrospective study

10.21203/rs.2.13704/v1 ◽

2019 ◽

Author(s):

Hsien-Fu Chiu ◽

Mei-Chin Wen ◽

Ming-Ju Wu ◽

Cheng-Hsu Chen ◽

Tung-Min Yu ◽

...

Keyword(s):

Renal Transplant ◽

Graft Loss ◽

Renal Transplant Recipients ◽

Kidney Graft ◽

Supportive Treatment ◽

Aggressive Treatment ◽

Transplant Recipients ◽

Antibody Mediated Rejection ◽

Group 2 ◽

Group 1

Abstract Background: A plethora of evidences suggest that the most important cause of late graft loss in renal transplant recipients is chronic active antibody-mediated rejection. However, there are no consensus on treatment strategies. Methods: We retrospectively analyzed clinical and pathological data of renal transplant recipients who received kidney graft biopsy with confirmed diagnosis of chronic active antibody-mediated rejection in the past 7 years. The patients were divided into two groups according to treatment strategy: Group 1: aggressive treatment (double filtration plasmapheresis and one of the followings: rituximab, intravenous immunoglobulin, antithymogycte globulin, bortezomib, or methylprednisolone pulse therapy); and group 2: supportive treatment. Results: From February 2009 to December 2017, a total of 82 graft biopsies with diagnosis of chronic active antibody mediated rejection were identified. Kaplan-Meier analysis of death-censored graft survival showed a worse survival in group 2 (P = 0.015 by log-rank test). Adverse event-free survival was lower in group 1, whereas patient survival was no significant different. Proteinuria and supportive treatment were independent risk factors for graft loss in multivariate analysis. Conclusions: Aggressive treatment was associated with better graft outcome. However, higher incidence of adverse events merit personalized treatment, especially for those with higher risk of infection. Appropriate prophylactic antibiotics are recommended for aggressive treatment patients.

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Flow Cytometric Crossmatching in Primary Renal Transplant Recipients with a Negative Anti-Human Globulin Enhanced Cytotoxicity Crossmatch

Journal of the American Society of Nephrology ◽

10.1681/asn.v12122807 ◽

2001 ◽

Vol 12 (12) ◽

pp. 2807-2814 ◽

Cited By ~ 4

Author(s):

Martin Karpinski ◽

David Rush ◽

John Jeffery ◽

Markus Exner ◽

Heinz Regele ◽

...

Keyword(s):

T Cell ◽

Renal Transplant ◽

Graft Loss ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Hla Antibodies ◽

Antibody Mediated Rejection ◽

Flow Cytometric ◽

Increased Risk ◽

Early Graft

ABSTRACT. Flow cytometric crossmatching (FCXM) and panel reactive antibody (PRA) screening techniques are more sensitive than anti-human globulin enhanced cytotoxicity (AHG-CDC) techniques at detecting anti-HLA antibodies. The clinical significance of a positive FCXM in primary renal transplant recipients with a negative AHG-CDC crossmatch is unclear. We performed retrospective FCXM and flow cytometric panel reactive antibody (FlowPRA) determinations in primary renal transplant recipients with a negative T cell AHG-CDC crossmatch and a negative B cell CDC crossmatch pretransplant. Eighteen (13%) of 143 patients exhibited a positive retrospective T cell FCXM. Of these patients, six (33%) experienced early graft loss with explant histology, demonstrating antibody-mediated rejection in five of six cases. The 12 patients with positive T cell FCXM who maintained their grafts experienced more adverse events posttransplant, including more early, steroid-resistant, and recurrent rejection. Furthermore, in a subgroup of patients undergoing protocol biopsies, those with a positive T cell FCXM exhibited more subclinical rejection. Anti-HLA antibodies were detected by FlowPRA in all 18 patients with a positive T cell FCXM, whereas AHG-CDC PRA detected antibodies in only 8 of 18 patients. Therefore, flow cytometric techniques identify sensitized primary renal transplant recipients undetected by AHG-CDC techniques. In those patients, a positive T cell FCXM is associated with an increased risk of early graft loss due to antibody-mediated rejection and may represent a relative contraindication to transplantation. Moreover, those patients are also at increased risk of severe and recurrent rejection, which may carry implications for long-term graft outcomes.

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Treatment of chronic active antibody-mediated rejection in renal transplant recipients – a single center retrospective study

BMC Nephrology ◽

10.1186/s12882-019-1672-8 ◽

2020 ◽

Vol 21 (1) ◽

Cited By ~ 1

Author(s):

Hsien-Fu Chiu ◽

Mei-Chin Wen ◽

Ming-Ju Wu ◽

Cheng-Hsu Chen ◽

Tung-Min Yu ◽

...

Keyword(s):

Renal Transplant ◽

Graft Loss ◽

Rank Test ◽

Renal Transplant Recipients ◽

Supportive Treatment ◽

Aggressive Treatment ◽

Transplant Recipients ◽

Antibody Mediated Rejection ◽

Group 2 ◽

Group 1

Abstract Background Chronic active antibody-mediated rejection is a major etiology of graft loss in renal transplant recipients. However, there is no consensus on the optimal treatment strategies. Methods Computerized records from Taichung Veterans General Hospital were collected to identify renal transplant biopsies performed in the past 7 years with a diagnosis of chronic active antibody-mediated rejection. The patients were divided into two groups according to treatment strategy: Group 1 received aggressive treatment (double filtration plasmapheresis and one of the followings: rituximab, intravenous immunoglobulin, antithymogycte globulin, bortezomib, or methylprednisolone pulse therapy); and group 2 received supportive treatment. Results From February 2009 to December 2017, a total of 82 patients with biopsy-proven chronic antibody mediated rejection were identified. Kaplan-Meier analysis of death-censored graft survival showed a worse survival in group 2 (P = 0.015 by log-rank test). Adverse event-free survival was lower in group 1, whereas patient survival was not significantly different. Proteinuria and supportive treatment were independent risk factors for graft loss in multivariate analysis. Conclusions Aggressive treatment was associated with better graft outcome. However, higher incidence of adverse events merit personalized treatment, especially for those with higher risk of infection. Appropriate prophylactic antibiotics are recommended for patients undergoing aggressive treatment.

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