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chronic renal allograft dysfunction

Shigeo Hara
Chronic rejection in renal transplantation clinically manifests as slow deterioration in allograft function and is a major contributor of late renal graft loss. Most cases of chronic rejection involve chronic antibody-mediated rejection (ABMR) triggered by the interaction of donor-specific alloantibodies with endothelial cells of the microcirculation. The evolution of the Banff classification involved a major revision of the ABMR criteria during the 2000s and led to the inclusion of detailed pathological characteristics of chronic ABMR in the 2013 Banff scheme, including microcirculation damage observed as newly formed basement membranes and arterial fibrous intimal proliferation...
November 16, 2016: Clinical and Experimental Nephrology
Ewa Dąbrowska-Żamojcin, Violetta Dziedziejko, Krzysztof Safranow, Leszek Domański, Sylwia Słuczanowska-Głabowska, Andrzej Pawlik
INTRODUCTION: STAT4 (signal transducer and activator of transcription 4) is involved in the regulation of innate and adaptive immune responses. Some studies have suggested that STAT4 may be involved in the immune response after graft transplantation. Several polymorphisms in the STAT4 gene have been identified. The most commonly studied polymorphism in the STAT4 gene is rs7574865. In our study, we examined whether this polymorphism is associated with the early and late functions of renal allografts...
2016: Central-European Journal of Immunology
Héloise Cardinal, Mélanie Dieudé, Marie-Josée Hébert
Antibodies that are specific to organ donor HLA have been involved in the majority of cases of antibody-mediated rejection in solid organ transplant recipients. However, recent data show that production of non-HLA autoantibodies can occur before transplant in the form of natural autoantibodies. In contrast to HLAs, which are constitutively expressed on the cell surface of the allograft endothelium, autoantigens are usually cryptic. Tissue damage associated with ischemia-reperfusion, vascular injury, and/or rejection creates permissive conditions for the expression of cryptic autoantigens, allowing these autoantibodies to bind antigenic targets and further enhance vascular inflammation and renal dysfunction...
October 17, 2016: Journal of the American Society of Nephrology: JASN
Wael M Hamza, Hanan H Ali, Samia M Gabal, Sawsan A Fadda
The chronic dysfunction stands as the most common cause of renal allograft loss. During the nineties of the past century, this condition was referred to as chronic allograft nephropathy (CAN). Since 2005, CAN has been assigned by the eighth Banff schema to four main categories via histopathological and immunohistochemical findings including chronic antibodymediated rejection (CAMR), chronic T-cell-mediated rejection (CTMR), chronic cyclosporine toxicity (CNITOX), and "interstitial fibrosis (IF)/tubular atrophy; not otherwise specified (NOS)" to eliminate the term CAN...
September 2016: Saudi Journal of Kidney Diseases and Transplantation
Jiexiu Zhang, Zijie Wang, Zhen Xu, Zhijian Han, Jun Tao, Pei Lu, Zhengkai Huang, Wanli Zhou, Chunchun Zhao, Ruoyun Tan, Min Gu
BACKGROUND Chronic allograft dysfunction (CAD) is the major factor endangering the long-term allograft survival in kidney transplantation. The mechanisms of CAD remain unclear. MATERIAL AND METHODS A total of 64 renal transplant recipients were enrolled in our study and divided into a stable group and CAD group according to their allograft function. A group of 32 normal controls (healthy volunteers) were also included. An ELISA was used to detect serum interleukin-33 (IL-33), IL-2, IL-4, IL-10, IL-17, and interferon-gamma (IFN-γ)...
October 4, 2016: Annals of Transplantation: Quarterly of the Polish Transplantation Society
Darlene Vigil, Nikifor K Konstantinov, Marc Barry, Antonia M Harford, Karen S Servilla, Young Ho Kim, Yijuan Sun, Kavitha Ganta, Antonios H Tzamaloukas
Nephropathy secondary to BK virus, a member of the Papoviridae family of viruses, has been recognized for some time as an important cause of allograft dysfunction in renal transplant recipients. In recent times, BK nephropathy (BKN) of the native kidneys has being increasingly recognized as a cause of chronic kidney disease in patients with solid organ transplants, bone marrow transplants and in patients with other clinical entities associated with immunosuppression. In such patients renal dysfunction is often attributed to other factors including nephrotoxicity of medications used to prevent rejection of the transplanted organs...
September 24, 2016: World Journal of Transplantation
Shi Deng, Tao Jin, Li Zhang, Hong Bu, Peng Zhang
Chronic renal allograft dysfunction (CRAD) is the most common cause of graft failure following renal transplantation. However, the underlying mechanisms remain to be fully elucidated. Immunosuppressants and hyperlipidemia are associated with renal fibrosis following long‑term use. The present study aimed to determine the effects of tacrolimus (FK506) and lipid metabolism disorder on CRAD. In vitro and in vivo models were used for this investigation. Cells of the mouse proximal renal tubular epithelial cell strain, NRK‑52E, were cultured either with oxidized low‑density lipoprotein (ox‑LDL), FK506, ox‑LDL combined with FK506, or vehicle, respectively...
November 2016: Molecular Medicine Reports
Q Yan, H Jiang, B Wang, W Sui, H Zhou, G Zou
BACKGROUND: To investigate the expression of RANTES (regulated upon activation, normal T-cell-expressed and -secreted) and monocyte chemoattractant protein-1 (MCP-1) in renal allografts with chronic renal allograft dysfunction (CRAD), and explore its relationship with interstitial fibrosis and tubular atrophy (IF/TA). METHODS: An immunohistochemical assay and computer-assisted, genuine colored image analysis system were used to detect the expression of RANTES and MCP-1 in renal allografts with CRAD...
July 2016: Transplantation Proceedings
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
Niels V Rekers, J W de Fijter, Frans H J Claas, Michael Eikmans
Ever since the first successful kidney transplantation, the occurrence of acute rejection has been a dominant risk factor for adverse graft outcome, as it is associated with reduced graft survival and the development of chronic transplant dysfunction. Although the majority of acute renal allograft rejection episodes can be adequately treated with glucocorticoid therapy, 25 to 30% of the rejection episode cannot be reversed with glucocorticoids alone. At present, the diagnosis of steroid resistance primarily relies on post-transplantation follow-up of clinical parameters reflecting renal allograft function...
September 2016: Transplant Immunology
Jingxin Xie, Xueyi Li, Dan Meng, Qiujuan Liang, Xinhong Wang, Li Wang, Rui Wang, Meng Xiang, Sifeng Chen
Renal transplantation is the treatment of choice for end-stage renal failure. Although acute rejection is not a major issue anymore, chronic rejection, especially vascular rejection, is still a major factor that might lead to allograft dysfunction on the long term. The role of the local immune-regulating cytokine interleukin-10 (IL-10) in chronic renal allograft is unclear. Many clinical observations showed that local IL-10 level was negatively related to kidney allograft function. It is unknown this negative relationship was the result of immunostimulatory property or insufficient immunosuppression property of local IL-10...
August 2016: Immunology Letters
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...
November 2016: Nephrology, Dialysis, Transplantation
L Ghisdal, C Baron, Y Lebranchu, O Viklický, A Konarikova, M Naesens, D Kuypers, M Dinic, E Alamartine, G Touchard, T Antoine, M Essig, J P Rerolle, P Merville, J L Taupin, Y Le Meur, A Grall-Jezequel, F Glowacki, C Noël, C Legendre, D Anglicheau, N Broeders, W Coppieters, E Docampo, M Georges, Z Ajarchouh, A Massart, J Racapé, D Abramowicz, M Abramowicz
Acute renal rejection is a major risk factor for chronic allograft dysfunction and long-term graft loss. We performed a genome-wide association study to detect loci associated with biopsy-proven acute T cell-mediated rejection occurring in the first year after renal transplantation. In a discovery cohort of 4127 European renal allograft recipients transplanted in eight European centers, we used a DNA pooling approach to compare 275 cases and 503 controls, on Illumina 2·5 M arrays. In an independent replication cohort of 2765 patients transplanted in two European countries, we identified 313 cases and 531 controls, in whom we genotyped individually the most significant SNPs from the discovery cohort...
June 7, 2016: American Journal of Transplantation
Zoltan H Endre, Mangalee Fernando
Diagnosis of transplant dysfunction usually requires kidney biopsy. Sidgel et al. compared urinary proteomics with matched kidney biopsies to develop a biomarker panel to differentiate acute rejection, BK viral nephropathy, and chronic allograft nephropathy. The results suggest that monitoring a panel of urinary peptides may ultimately facilitate noninvasive diagnosis and management of common transplant complications.
June 2016: Kidney International
Engin Melek, Esra Baskin, Kaan Gulleroglu, Umut Selda Bayrakci, Gokhan Moray, Mehmet Haberal
OBJECTIVES: Chronic kidney disease caused by lower urinary tract abnormalities is a significant complication in pediatric care. Although there are conflicting reports about clinical outcomes in the past, favorable outcomes have been reported in recent years. Despite this, many centers still refrain from performing renal transplant in these patients. Here, we compared clinical outcomes of renal transplant recipients with and without lower urinary tract abnormalities. MATERIALS AND METHODS: Our study included 71 renal transplant recipients who were divided into 3 groups: 17 patients with abnormal lower urinary tracts having vesicoureteral reflux (group 1), 7 patients with abnormal lower urinary tracts having bladder dysfunction (group 2), and 47 patients with anatomically and functionally normal lower urinary tracts (group 3)...
May 2, 2016: Experimental and Clinical Transplantation
Clement Wilfred Devadass, Aruna Vishwanth Vanikar, Lovelesh Kumar Nigam, Kamal Vinod Kanodia, Rashmi Dalsukhbhai Patel, Kyasakkala Sannaboraiah Vinay, Himanshu V Patel
INTRODUCTION: Biopsy remains gold standard for diagnosis of Graft Dysfunction (GD). It guides clinical management, provides valuable insights into pathogenesis of early and late allograft injury and is indispensable for distinguishing rejection from non- rejection causes of GD. AIM: The primary aim of the study was to evaluate the diverse histomorphological lesions in renal allograft biopsy (RAB). Further, we determined the frequency of peritubular capillary (PTC) C4d positivity and its correlation with microvascular inflammation in Antibody Mediated Rejection (AMR)...
March 2016: Journal of Clinical and Diagnostic Research: JCDR
L García-Covarrubias, E Ventura, V Soto, E González, A García, J C Aguilar, J M Torres, H Hinojosa, P Fragoso, J De Los Santos, D Ortuño, P San Cristóbal, H Díliz
INTRODUCTION: A lot of evidence has demonstrated the importance of different cytokines in acute renal rejection. Previous studies have examined the presence or absence of interleukin (IL)-10 in related immunopathologic rejection grafts as well as other interleukins. Studies in human transplantation show elevated levels of IL-10 and gamma interferon (INF-γ) in inflammation and rejection. OBJECTIVE: The objective of this study was to demonstrate the lack of association of elevated urinary levels of IL-10 and IFN in the presence of active inflammation...
March 2016: Transplantation Proceedings
Ryan J Goldberg, Francis L Weng, Praveen Kandula
Allograft dysfunction after a kidney transplant is often clinically asymptomatic and is usually detected as an increase in serum creatinine level with corresponding decrease in glomerular filtration rate. The diagnostic evaluation may include blood tests, urinalysis, transplant ultrasonography, radionuclide imaging, and allograft biopsy. Whether it occurs early or later after transplant, allograft dysfunction requires prompt evaluation to determine its cause and subsequent management. Acute rejection, medication toxicity from calcineurin inhibitors, and BK virus nephropathy can occur early or later...
May 2016: Medical Clinics of North America
Stephen D Marks
There have been marked improvements in the short- and long-term outcomes for children after renal transplantation over the past two decades with superior quality and quantity of life. It is encouraging to see increased patient and renal allograft survival rates with initially lower acute renal allograft rejection rates due to improved matching and immunosuppressive regimens. Unfortunately, longer-term renal allograft survival remains unchanged with chronic allograft injury from both immune and non-immune causes, resulting in chronic allograft dysfunction, morbidity from chronic kidney disease, and eventual renal allograft loss...
August 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Vural Taner Yilmaz, Gultekin Suleymanlar, Sadi Koksoy, Burak Veli Ulger, Sebahat Ozdem, Halide Akbas, Bahar Akkaya, Huseyin Kocak
INTRODUCTION: The aim of our study was to determine the effectiveness of immunoglobulin, rituximab and plasmapheresis in renal transplant patients with antibody mediated rejection (AMR). PATIENTS AND METHODS: Fourteen renal transplant patients with AMR were included in this study. The mean age of the patients was 33.9 ± 10.3 years and 10 (71.4%) of them were male. Lymphocyte cross match was negative for all patients and 10 (71.4%) of them were living donor transplants...
October 2016: Journal of Investigative Surgery: the Official Journal of the Academy of Surgical Research
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