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Mareen Matz, Christine Lorkowski, Katharina Fabritius, Kaiyin Wu, Birgit Rudolph, Stefan Frischbutter, Susanne Brakemeier, Jens Gaedeke, Hans-H Neumayer, Mir-Farzin Mashreghi, Klemens Budde
Cellular and antibody-mediated rejection processes and also interstitial fibrosis/tubular atrophy (IFTA) lead to allograft dysfunction and loss. The search for accurate, specific and non-invasive diagnostic tools is still ongoing and essential for successful treatment of renal transplanted patients. Molecular markers in blood cells and serum may serve as diagnostic tools but studies with high patient numbers and differential groups are rare. We validated the potential value of several markers on mRNA level in blood cells and serum protein level in 166 samples from kidney transplanted patients under standard immunosuppressive therapy (steroids±mycophenolic acid±calcineurin inhibitor) with stable graft function, urinary tract infection (UTI), IFTA, antibody-mediated rejection (ABMR), and T-cell-mediated rejection (TCMR) applying RT-PCR and ELISA...
September 29, 2016: Transplant Immunology
Guo-Sheng Wu
Antibody-mediated rejection (ABMR) has increasingly emerged as an important cause of allograft loss after intestinal transplantation (ITx). Compelling evidence indicates that donor-specific antibodies can mediate and promote acute and chronic rejection after ITx. However, diagnostic criteria for ABMR after ITx have not been established yet and the mechanisms of antibody-mediated graft injury are not well-known. Effective approaches to prevent and treat ABMR are required to improve long-term outcomes of intestine recipients...
September 24, 2016: World Journal of Transplantation
Waqas Khan Kayani, Erum Dilshad, Tanveer Ahmed, Hammad Ismail, Bushra Mirza
BACKGROUND: Ajuga bracteosa has been extensively used traditionally for the treatment of a variety of diseases. The aim of the study was to scientifically validate the wide-scale exploitation of A. bracteosa in folk medicine various in vitro and in vivo assays. Moreover, these activities were related to the intrinsic biologically active phytoecdysteroids of A. bracteosa. METHODS: Aerial and root parts of A. bracteosa were first extracted separately with chloroform (AbCA and AbCR) and the residue was again extracted with methanol (AbMA and AbMR)...
September 27, 2016: BMC Complementary and Alternative Medicine
Mareen Matz, Christine Lorkowski, Katharina Fabritius, Pawel Durek, Kaiyin Wu, Birgit Rudolph, Hans-H Neumayer, Mir-Farzin Mashreghi, Klemens Budde
The potential diagnostic value of circulating free miRNAs in plasma compared to miRNA expression in blood cells for rejection processes after kidney transplantation is largely unknown, but offers the potential for better and timely diagnosis of acute rejection. Free microRNA expression of specific blood cell markers was measured in 160 plasma samples from kidney transplant patients under standard immunosuppressive therapy (steroids±mycophenolic acid±calcineurin inhibitor) with stable graft function, urinary tract infection, interstitial fibrosis and tubular atrophy, antibody-mediated rejection (ABMR), Borderline (Banff3), tubulo-interstitial (Banff4-I) and vascular rejection (Banff4-II/III) applying RT-PCR...
September 20, 2016: Transplant Immunology
Sourabh Chand, David Atkinson, Clare Collins, David Briggs, Simon Ball, Adnan Sharif, Kassiani Skordilis, Bindu Vydianath, Desley Neil, Richard Borrows
BACKGROUND: Causes of "true" late kidney allograft failure remain unclear as study selection bias and limited follow-up risk incomplete representation of the spectrum. METHODS: We evaluated all unselected graft failures from 2008-2014 (n = 171; 0-36 years post-transplantation) by contemporary classification of indication biopsies "proximate" to failure, DSA assessment, clinical and biochemical data. RESULTS: The spectrum of graft failure changed markedly depending on the timing of allograft failure...
2016: PloS One
Saif A Khan, Dawood Al-Riyami, Yasser W Al-Mula Abed, Saja Mohammed, Marwa Al-Riyami, Nabil M Al-Lawati
Antibody-mediated rejection (ABMR) jeopardises short- and long-term transplant survival and remains a challenge in the field of organ transplantation. We report the first use of the anticomplement agent eculizumab in Oman in the treatment of a 61-year-old female patient with ABMR following a living unrelated kidney transplant. The patient was admitted to the Sultan Qaboos University Hospital in Muscat, Oman, in 2013 on the eighth day post-transplantation with serum creatinine (Cr) levels of 400 µmol/L which continued to rise, necessitating haemodialysis...
August 2016: Sultan Qaboos University Medical Journal
Tristan Legris, Christophe Picard, Dilyana Todorova, Luc Lyonnet, Cathy Laporte, Chloé Dumoulin, Corinne Nicolino-Brunet, Laurent Daniel, Anderson Loundou, Sophie Morange, Stanislas Bataille, Henri Vacher-Coponat, Valérie Moal, Yvon Berland, Francoise Dignat-George, Stéphane Burtey, Pascale Paul
Although kidney transplantation remains the best treatment for end-stage renal failure, it is limited by chronic humoral aggression of the graft vasculature by donor-specific antibodies (DSAs). The complement-independent mechanisms that lead to the antibody-mediated rejection (ABMR) of kidney allografts remain poorly understood. Increasing lines of evidence have revealed the relevance of natural killer (NK) cells as innate immune effectors of antibody-dependent cellular cytotoxicity (ADCC), but few studies have investigated their alloreactive potential in the context of solid organ transplantation...
2016: Frontiers in Immunology
C Wiebe, A J Gareau, D Pochinco, I W Gibson, J Ho, P E Birk, T Blydt-Hasen, M Karpinski, A Goldberg, L Storsley, D N Rush, P W Nickerson
De novo donor-specific antibodies (dnDSAs) that develop after renal transplantation are independent predictors of allograft loss. However, it is unknown if dnDSA C1q status or titer at the time of first detection can independently predict allograft loss. In a consecutive cohort of 508 renal transplant recipients, 70 developed dnDSAs. Histologic and clinical outcomes were correlated with the C1q assay or dnDSA titer. C1q positivity correlated with dnDSA titer (p < 0.01) and mean fluorescence intensity (p < 0...
August 19, 2016: American Journal of Transplantation
Martin Schiemann, Elisabeth Puchhammer-Stöckl, Farsad Eskandary, Philip Kohlbeck, Susanne Rasoul-Rockenschaub, Andreas Heilos, Nicolas Kozakowski, Irene Görzer, Željko Kikić, Harald Herkner, Georg A Böhmig, Gregor Bond
BACKGROUND: Antibody-mediated rejection (ABMR) represents 1 of the cardinal causes of late allograft loss after kidney transplantation and there is great need for noninvasive tools improving early diagnosis of this rejection type. One promising strategy might be the quantification of peripheral blood DNA levels of the highly prevalent and apathogenic Torque Teno virus (TTV), which might mirror the overall level of immunosuppression and thus help determine the risk of alloimmune response...
August 12, 2016: Transplantation
Seung Hwan Song, Borae G Park, Juhan Lee, Myoung Soo Kim, Yu Seun Kim, Hyon-Suk Kim
BACKGROUND: Traditionally, the presence of antibodies against human leukocyte antigen (HLA)-C and DP was considered to be associated with only a low risk of antibody-mediated rejection (ABMR) in kidney transplantation (KT), because the antigenicities of these proteins are weak. However, the clinical effects of HLA-C and -DP donor-specific HLA antibodies (DSHAs) have recently been reevaluated. METHODS: Here, we report the case of a retransplant patient with positive flow cytometry crossmatch (FCXM) and high level of HLA-DP DSHA who was desensitized using rituximab, plasmapheresis, and intravenous immunoglobulin...
August 2016: Medicine (Baltimore)
A Furmańczyk-Zawiska, A Urbanowicz, A Perkowska-Ptasińska, T Bączkowska, A Sadowska, S Nazarewski, A Chmura, M Durlik
BACKGROUND: Antibody-mediated rejection (ABMR) has emerged as the leading cause of renal graft loss. The optimal treatment protocol in ABMR remains unknown. This study aimed to assess the efficacy of intravenous immunoglobulin (IVIG) for treatment of ABMR in renal recipients. METHODS: Thirty-nine ABO-compatible cross-match-negative renal recipients with biopsy-proven ABMR composed the study group. Pulses of methylprednisolone (MP) and appropriate enhancement of net state of immunosuppression were applied in all individuals; 17/39 recipients were administered IVIG (IVIG group); the remaining 22/39 patients, identified to be nonadherent or unsatisfactorily immunosuppressed, were kept on the initial treatment (MP group)...
June 2016: Transplantation Proceedings
Kevin V Chow, Shaun M Flint, Angeline Shen, Anthony Landgren, Moira Finlay, Anand Murugasu, Rosemary Masterson, Peter Hughes, Solomon J Cohney
BACKGROUND: Excellent short-term results have been reported in ABO-incompatible renal transplant recipients (ABOi) managed solely with antibody removal and conventional immunosuppression. However, long-term clinical outcomes with this regimen and predictive information from protocol biopsies is lacking. METHODS: We compared outcome data in ABOi and ABO compatible (ABOc) recipients receiving this regimen approximately 4 years posttransplant, and histology from biopsies approximately 12 month posttransplant...
August 5, 2016: Transplantation
Elena Crespo, Silke Roedder, Tara Sigdel, Szu-Chuan Hsieh, Sergio Luque, Josep Maria Cruzado, Tim Q Tran, Josep Maria Grinyó, Minnie M Sarwal, Oriol Bestard
BACKGROUND: Subclinical acute rejection (sc-AR) is a main cause for functional decline and kidney graft loss and may only be assessed through surveillance biopsies. METHODS: The predictive capacity of 2 novel noninvasive blood biomarkers, the transcriptional kidney Solid Organ Response Test (kSORT), and the IFN-γ enzyme-linked immunosorbent spot assay (ELISPOT) assay were assessed in the Evaluation of Sub-Clinical Acute rejection PrEdiction (ESCAPE) Study in 75 consecutive kidney transplants who received 6-month protocol biopsies...
June 29, 2016: Transplantation
Philip F Halloran, Konrad S Famulski, Jeff Reeve
Progress in renal transplantation requires improved understanding and assessment of rejection and injury. Study of the relationship between gene expression and clinical phenotypes in kidney transplant biopsy samples has led to the development of a system that enables diagnoses of specific disease states on the basis of messenger RNA levels in the biopsy sample. Using this system we have defined the molecular landscape of T cell-mediated rejection (TCMR), antibody-mediated rejection (ABMR), acute kidney injury (AKI), and tubular atrophy and interstitial fibrosis...
September 2016: Nature Reviews. Nephrology
P F Halloran, K S Famulski, J Chang
Histologic diagnosis of antibody-mediated rejection (ABMR) in kidney transplant biopsies uses lesion score cutoffs such as 0 versus >0 rather than actual scores and requires donor-specific antibody (DSA); however, cutoffs lose information, and DSA is not always reliable. Using microarray-derived molecular ABMR scores as a histology-independent estimate of ABMR in 703 biopsies, we reassessed criteria for ABMR to determine relative importance of various lesions, the utility of equations using actual scores rather than cutoffs, and the potential for diagnosing ABMR when DSA is unknown or negative...
June 24, 2016: American Journal of Transplantation
Javier Gimeno, Dolores Redondo, María José Pérez-Sáez, Dolores Naranjo-Hans, Julio Pascual, Marta Crespo
BACKGROUND: The Banff classification is used worldwide to characterize pathological findings in renal allograft biopsies. During the 11th Banff meeting, relevant changes were introduced in the diagnostic criteria for Category 2 antibody-mediated rejection (ABMR). Here, we assess the effect of these changes on the diagnosis of late chronic ABMR. METHODS: Seventy-three indication renal graft biopsies (chronic dysfunction, proteinuria and/or the presence of de novo donor-specific antibodies) from 68 kidney transplant recipients initially classified following the Banff 2009 criteria were reviewed and reclassified as per the new Banff 2013 criteria...
June 16, 2016: Nephrology, Dialysis, Transplantation
Marianne Delville, Béatrice Charreau, Marion Rabant, Christophe Legendre, Dany Anglicheau
Antibody-mediated rejection (ABMR) is associated with poor transplant outcome. Pathogenic alloantibodies are usually directed against human leukocyte antigens (HLAs). Histological findings suggestive of ABMR usually demonstrate an anti-HLA donor-specific antibody (DSA)-mediated injury, while a small subset of patients develop acute dysfunction with histological lesions suggestive of ABMR in the absence of anti-HLA DSAs. Although this non-HLA ABMR is not well recognized by current diagnostic classifications, it is associated with graft dysfunction and allograft loss...
May 26, 2016: Human Immunology
S C Jordan, J Choi, J Kahwaji, A Vo
Therapeutic interventions aimed at the human complement system are recognized as potentially important strategies for the treatment of inflammatory and autoimmune diseases because there is often evidence of complement-mediated injury according to pathologic assessments. In addition, there are a large number of potential targets, both soluble and cell bound, that might offer potential for new drug development, but progress in this area has met with significant challenges. Currently, 2 drugs are approved aimed at inhibition of complement activation...
April 2016: Transplantation Proceedings
M S Uppin, S Gudithi, G Taduri, A K Prayaga, S B Raju
Renal allograft rejection is mediated by T-cells (T-cell mediated rejection) or by donor-specific antibodies (DSAs) (antibody mediated rejection, ABMR). Plasma cell-rich acute rejection (PCAR) is a unique entity due to its peculiar morphology and poor prognostic behavior. All allograft biopsies done at our center from January 2013 to October 2014 were reviewed, and seven were identified with a diagnosis of PCAR with antibody mediated rejection (ABMR). The allograft biopsies were classified as per the Banff 2007 schema...
May 2016: Indian Journal of Nephrology
Elisabeth Schwaiger, Farsad Eskandary, Nicolas Kozakowski, Gregor Bond, Željko Kikić, Daniel Yoo, Susanne Rasoul-Rockenschaub, Rainer Oberbauer, Georg A Böhmig
BACKGROUND: Apheresis-based desensitization allows for successful transplantation across major immunological barriers. For donor-specific antibody (DSA)- and/or crossmatch-positive transplantation, however, it has been shown that even intense immunomodulation may not completely prevent antibody-mediated rejection (ABMR). METHODS: In this study, we evaluated transplant outcomes in 101 DSA+ deceased donor kidney transplant recipients (transplantation between 2009 and 2013; median follow-up: 24 months) who were subjected to immunoadsorption (IA)-based desensitization...
August 2016: Nephrology, Dialysis, Transplantation
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