scholarly journals Intimal Arteritis and Microvascular Inflammation Are Associated With Inferior Kidney Graft Outcome, Regardless of Donor-Specific Antibodies

2021 ◽  
Vol 8 ◽  
Author(s):  
Marek Novotny ◽  
Petra Hruba ◽  
Martin Kment ◽  
Ludek Voska ◽  
Katerina Kabrtova ◽  
...  
Keyword(s):  
Graft Failure ◽  
Significant Risk ◽  
Kidney Graft ◽  
Free Survival ◽  
Antibody Mediated Rejection ◽  
Graft Outcome ◽  
Donor Specific Antibodies ◽  
Microvascular Inflammation ◽  
Transplant Glomerulopathy

Background: The prognostic role of intimal arteritis of kidney allografts in donor-specific antibody negative (DSA–) antibody-mediated rejection (ABMR) remains unclear.Methods: Seventy-two out of 881 patients who had undergone kidney transplantation from 2014 to 2017 exhibited intimal arteritis in biopsies performed during the first 12 months. In 26 DSA negative cases, the intimal arteritis was accompanied by tubulointerstitial inflammation as part of T cell-mediated vascular rejection (TCMRV, N = 26); intimal arteritis along with microvascular inflammation occurred in 29 DSA negative (ABMRV/DSA–) and 19 DSA positive cases (ABMRV, DSA+, N = 17). In 60 (83%) patients with intimal arteritis, the surveillance biopsies after antirejection therapy were performed. Hundred and two patients with non-vascular ABMR with DSA (ABMR/DSA+, N = 55) and without DSA (ABMR/DSA–, N = 47) served as controls. Time to transplant glomerulopathy (TG) and graft failure were the study endpoints.Results: Transplant glomerulopathy -free survival at 36 months was 100% in TCMRV, 85% in ABMR/DSA–, 65% in ABMRV/DSA-, 54% in ABMR/DSA+ and 31% in ABMRV/DSA+ (log rank p < 0.001). Death-censored graft survival at 36 months was 98% in ABMR/DSA-, 96% in TCMRV, 86% in ABMRV/DSA–, 79% in ABMR/DSA+, and 64% in ABMRV/DSA+ group (log rank p = 0.001). In surveillance biopsies, the resolution of rejection was found in 19 (90%) TCMRV, 14 (58%) ABMRV/DSA–, and only 4 (27%) ABMRV/DSA+ patients (p = 0.006). In the multivariable model, intimal arteritis as part of ABMR represented a significant risk for TG development (HR 2.1, 95% CI 1.2–3.8; p = 0.012) regardless of DSA status but not for graft failure at 36 months.Conclusions: Intimal arteritis as part of ABMR represented a risk for early development of TG regardless of the presence or absence of DSA. Intimal arteritis in DSA positive ABMR represented the high-risk phenotype.

scholarly journals Antibody-mediated rejection in heart transplantation

2021 ◽  
Vol 23 (4) ◽  
pp. 47-61
Author(s):  
V. S. Kvan ◽  
N. N. Koloskova ◽  
Yu. A. Kachanova ◽  
N. N. Sayfullina ◽  
A. Yu. Goncharova ◽  
...  
Keyword(s):  
Significant Risk ◽  
Significant Risk Factor ◽  
Humoral Immune ◽  
Treatment Regimens ◽  
Antibody Mediated Rejection ◽  
Humoral Immune System ◽  
Graft Vasculopathy ◽  
Donor Specific Antibodies ◽  
The Complement System

The role of antibody-mediated rejection in predicting survival among heart recipients has been studied in clinical transplantology for over 20 years. This condition is a significant risk factor for heart failure and graft vasculopathy. Antibody-mediated rejection results from activation of the humoral immune system and production of donorspecific antibodies that cause myocardial injury through the complement system. The presence of donor-specific antibodies is associated with lower allograft survival. Treatment of antibody-mediated rejection should take into account the rejection category and the presence or absence of graft dysfunction. The main principle of treatment is to suppress humoral immunity at different levels. World clinical practice has made significant inroads into the study of this issue. However, further research is required to identify and develop optimal treatment regimens for patients with humoral rejection in cardiac transplantation.

De Novo DQ Donor-Specific Antibodies Are Associated With a Significant Risk of Antibody-Mediated Rejection and Transplant Glomerulopathy

2012 ◽  
Vol 94 (2) ◽  
pp. 172-177 ◽  
Author(s):  
Michelle Willicombe ◽  
Paul Brookes ◽  
Ruhena Sergeant ◽  
Eva Santos-Nunez ◽  
Corinna Steggar ◽  
...  
Keyword(s):  
De Novo ◽  
Significant Risk ◽  
Specific Antibodies ◽  
Antibody Mediated Rejection ◽  
Donor Specific Antibodies ◽  
Transplant Glomerulopathy

Role of allograft nephrectomy following kidney graft failure: preliminary experience with pre-operative angiographic kidney embolization

2014 ◽  
Vol 28 (3) ◽  
pp. 379-385 ◽  
Author(s):  
Samer MT Al-Geizawi ◽  
Rajinder P. Singh ◽  
Jack M. Zuckerman ◽  
Jay A. Requarth ◽  
Alan C. Farney ◽  
...  
Keyword(s):  
Graft Failure ◽  
Kidney Graft ◽  
Allograft Nephrectomy

A Prospective Study Analyzing the Role of Donor-Specific Endothelial Cell Antibodies in Kidney Graft Outcome: A 3-Year Follow-Up.

2014 ◽  
Vol 98 ◽  
pp. 263
Author(s):  
S. Radhakrishnan ◽  
S. Shah ◽  
K. Haarberg ◽  
A. Safdi ◽  
W. Wegner ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Prospective Study ◽  
Kidney Graft ◽  
Graft Outcome ◽  
A Prospective Study

A Novel Treatment Protocol Successfully Prevented Graft Rejection and Improved Disease-Free Survival in Class 3 Children with Thalassemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 150-150 ◽  
Author(s):  
Javid Gaziev ◽  
Pietro Sodani ◽  
Antonella Isgrò ◽  
Marco Marziali ◽  
Maria Domenico Simone ◽  
...  
Keyword(s):  
Graft Failure ◽  
Conflicts Of Interest ◽  
Iron Concentration ◽  
Treatment Protocol ◽  
Significant Risk ◽  
Disease Free Survival ◽  
Platelet Recovery ◽  
Free Survival ◽  
Novel Treatment ◽  
Disease Free

Abstract Abstract 150 Background: Historically, bone marrow transplantation (BMT) in class 3 thalassemia patients has been associated with a significant risk of graft failure and transplant-related mortality leading to lower disease-free survival. Our initial study showed that class 3 patients treated with a new treatment protocol (Pc 26) had an improved survival and decreased rejection rates compared with previous protocols (Blood 2004;104:1201). An interim analysis of our subsequent experience with BMT in class 3 patients treated with Pc26 showed an increased rejection rate which has prompted us to modify the protocol to overcome this complication. Since February 2007 we have been using the modified Pc26 (Pc26m) in class 3 patients. Patients and Methods: Between June 2004 and July 2011 a total of 45 class 3 patients with median age of 10 years (range, 5–16) were treated: 26 patients with original (Pc26) and 19 patients with modified protocol (Pc26m). The two groups were well balanced in respect to baseline demographic and clinical characteristics. Patients had severe iron overload with median serum ferritin and liver iron concentration of 2626 ng/mL (range, 777–10222) and 20,8 mg/g dry weight (range, 5–40.7), respectively. Median liver fibrosis score was 2 (range, 1–5). There were 5 patients with HCV, and 1 with hepatitis B virus (HB Ag-positive) at the time of transplantation. The median number of packed RBC transfusions was 140 units (range, 25–307). The Pc26m consisted of pre-conditioning and conditioning phases. This novel treatment regimen involved an intensified preparation with 3 mg/kg of azathioprine and 30 mg/kg hydroxyurea daily from day -45 from the transplant, fludarabine 30 mg/m2 from day -16 through day -12, followed by the administration of weight based busilvex (since 2006), Thiotepa 10 mg/kg/day and CY 160 mg/kg total dose. GVHD prophylaxis consisted of CSA, low-dose methylprednisolone, and a modified “short course” of methotrexate (MTX). Results: Four of 26 patients treated with Pc26 and none of 19 patients treated with Pc26m had graft failure. The median time of neutrophil recovery (ANC>500 ×109/L) and platelet recovery (>20 ×109/L) were similar in both group of patients. Transplant outcomes are shown in Table 1. Overall treatment protocol was well tolerated without any significant toxicity. None of the patients had grade 4 toxicity. Most frequent grade 3 toxicity was AST and ALT elevations. Five patients, 3 treated with Pc26 and 2 with Pc26m had grade 2 hemorrhagic cystitis. One patient in each group had moderate liver VOD resolved with supportive care. Two patients in Pc26 group and one in the Pc26m group had pneumonia. There were 3 patients with bacteremia: 2 in Pc26 and one in Pc26m treated patients. The incidence of CMV reactivation was similar in both group. Conclusion: This study shows that the modified treatment protocol for class 3 thalassemia patients is highly effective in terms of graft failure leading to a high DFS rate which is comparable to those obtained in class 1 and class 2 patients. It also suggests that this intensified preparative regimen aimed at reducing a large disease burden and increasing immunosuppression over time thus avoiding unacceptable peritransplant drug toxicity is essential for minimizing graft failure in these high-risk patients. Disclosure: No relevant conflict of interest to declare. Disclosures: No relevant conflicts of interest to declare.

Comparing transplant glomerulopathy in the absence of C4d deposition and donor-specific antibodies to chronic antibody-mediated rejection

2014 ◽  
Vol 28 (10) ◽  
pp. 1148-1154 ◽  
Author(s):  
Irina B. Torres ◽  
Maite Salcedo ◽  
Francesc Moreso ◽  
Joana Sellarés ◽  
Eva Castellá ◽  
...  
Keyword(s):  
Specific Antibodies ◽  
Antibody Mediated Rejection ◽  
Donor Specific Antibodies ◽  
Transplant Glomerulopathy
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