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Transplant glomerulopathy

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https://www.readbyqxmd.com/read/28446536/donor-specific-antibodies-in-kidney-transplant-recipients
#1
REVIEW
Rubin Zhang
Donor-specific antibodies have become an established biomarker predicting antibody-mediated rejection. Antibody-mediated rejection is the leading cause of graft loss after kidney transplant. There are several phenotypes of antibody-mediated rejection along post-transplant course that are determined by the timing and extent of humoral response and the various characteristics of donor-specific antibodies, such as antigen classes, specificity, antibody strength, IgG subclasses, and complement binding capacity...
April 26, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28444814/chronic-antibody-mediated-rejection-in-nonhuman-primate-renal-allografts-validation-of-human-histological-and-molecular-phenotypes
#2
B A Adam, R N Smith, I A Rosales, M Matsunami, B Afzali, T Oura, A B Cosimi, T Kawai, R B Colvin, M Mengel
Molecular testing represents a promising adjunct for the diagnosis of antibody-mediated rejection (AMR). Here we apply a novel gene expression platform in sequential formalin-fixed paraffin-embedded (FFPE) samples from nonhuman primate (NHP) renal transplants. We analyzed 34 previously-described gene transcripts related to AMR in humans in 197 archival NHP samples, including 102 from recipients that developed chronic AMR, 80 from recipients without AMR, and 15 normal native nephrectomies. Three endothelial genes (VWF, DARC, CAV1), derived from 10-fold cross-validation ROC curve analysis, demonstrated excellent discrimination between AMR and non-AMR samples (AUC=0...
April 26, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28356669/c3-glomerulopathy-associated-to-multiple-myeloma-successfully-treated-by-autologous-stem-cell-transplant
#3
M A Hamzi, A Zniber, G E Badaoui, E Mahtat, Z Alhamany, R Bayahia, N Ouzeddoun
A 32-year-old male presented with advanced renal failure and nephrotic proteinuria due to lambda light chain multiple myeloma. Renal biopsy showed a proliferative glomerulonephritis with isolated C3 deposits. Renal recovery was obtained after chemotherapy and autologous stem cell transplant. We review previously described cases of C3 glomerulopathy associated with monoclonal gammopathy.
March 2017: Indian Journal of Nephrology
https://www.readbyqxmd.com/read/28337616/follow-up-results-of-patients-with-adck4-mutations-and-the-efficacy-of-coq10-treatment
#4
Mustafa Atmaca, Bora Gulhan, Emine Korkmaz, Mihriban Inozu, Oguz Soylemezoglu, Cengiz Candan, Aysun Karabay Bayazıt, Ahmet Midhat Elmacı, Gonul Parmaksiz, Ali Duzova, Nesrin Besbas, Rezan Topaloglu, Fatih Ozaltin
BACKGROUND: ADCK4-related glomerulopathy is an important differential diagnosis in adolescents with steroid-resistant nephrotic syndrome (SRNS) and/or chronic kidney disease (CKD) of unknown origin. We screened adolescent patients to determine the frequency of ADCK4 mutation and the efficacy of early CoQ10 administration. METHODS: A total of 146 index patients aged 10-18 years, with newly diagnosed non-nephrotic proteinuria, nephrotic syndrome, or chronic renal failure and end-stage kidney disease (ESKD) of unknown etiology were screened for ADCK4 mutation...
March 24, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28331448/antibody-mediated-rejection-a-review
#5
Jorge Carlos Garces, Sixto Giusti, Catherine Staffeld-Coit, Humberto Bohorquez, Ari J Cohen, George E Loss
BACKGROUND: Chronic antibody injury is a serious threat to allograft outcomes and is therefore the center of active research. In the continuum of allograft rejection, the development of antibodies plays a critical role. In recent years, an increased recognition of molecular and histologic changes has provided a better understanding of antibody-mediated rejection (AMR), as well as potential therapeutic interventions. However, several pathways are still unknown, which accounts for the lack of efficacy of some of the currently available agents that are used to treat rejection...
2017: Ochsner Journal
https://www.readbyqxmd.com/read/28298181/early-onset-of-adck4-glomerulopathy-with-renal-failure-a-case-report
#6
Ksenija Lolin, Benedetta D Chiodini, Elise Hennaut, Brigitte Adams, Karin Dahan, Khalid Ismaili
BACKGROUND: We present a rare early presentation of a ADCK4-related glomerulopathy. This case is of interest as potentially treatable if genetic results are timely obtained. CASE PRESENTATION: We report the case of a 5-year-old boy who was identified with significant proteinuria by a urinary routine screening program for school children. Physical examination revealed dysplastic ears and abnormal folded pinna. Albumin level was 41 g/L (39-53 g/L), and urine proteins/creatinine ratio was 2...
March 16, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28260442/nephrotic-syndrome-after-hematopoietic-stem-cell-transplant-outcomes-in-iran
#7
Fereshteh Saddadi, Ali Alidadi, Monir Hakemi, Babak Bahar
OBJECTIVES: Patients undergoing hematopoietic stem cell transplant have an elevated incidence of acute renal failure. However, the incidence of nephritic syndrome due to graft-versus-host disease is growing and is independently associated with chronic renal disease after this procedure. MATERIALS AND METHODS: We conducted a prospective study to examine the risk of chronic kidney disease in glomerulopathy patients following hematopoietic stem cell transplant with a follow-up of 10 years...
February 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28255002/antibody-mediated-rejection-due-to-preexisting-versus-de-novo-donor-specific-antibodies-in-kidney-allograft-recipients
#8
Olivier Aubert, Alexandre Loupy, Luis Hidalgo, Jean-Paul Duong van Huyen, Sarah Higgins, Denis Viglietti, Xavier Jouven, Denis Glotz, Christophe Legendre, Carmen Lefaucheur, Philip F Halloran
Antibody-mediated rejection (ABMR) can occur in patients with preexisting anti-HLA donor-specific antibodies (DSA) or in patients who develop de novo DSA. However, how these processes compare in terms of allograft injury and outcome has not been addressed. From a cohort of 771 kidney biopsy specimens from two North American and five European centers, we performed a systematic assessment of clinical and biologic parameters, histopathology, circulating DSA, and allograft gene expression for all patients with ABMR (n=205)...
March 2, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28252564/diffuse-extent-of-peritubular-capillaritis-in-late-antibody-mediated-rejection-associations-with-levels-of-donor-specific-antibodies-and-chronic-allograft-injury
#9
Nicolas Kozakowski, Farsad Eskandary, Harald Herkner, Gregor Bond, Rainer Oberbauer, Heinz Regele, Georg A Böhmig, Željko Kikić
BACKGROUND: Recently, diffuse peritubular capillaritis (ptc) has been suggested to independently predict chronic transplant injury and loss, and although the ptc score is a diagnostic criterion for antibody-mediated rejection, the utility of diffuse ptc is under debate. METHODS: We evaluated the diagnostic value of ptc characteristics in this cross-sectional study including 85 biopsies of patients with donor-specific antibodies (DSA). Biopsies were reevaluated for the extent (diffuse vs focal), score and leukocytic composition in relation to DSA binding strength (mean fluorescence intensity [MFI]_max)...
May 2017: Transplantation
https://www.readbyqxmd.com/read/28242845/focal-segmental-glomerulosclerosis
#10
Avi Z Rosenberg, Jeffrey B Kopp
Focal segmental glomerulosclerosis (FSGS) is a leading cause of kidney disease worldwide. The presumed etiology of primary FSGS is a plasma factor with responsiveness to immunosuppressive therapy and a risk of recurrence after kidney transplant-important disease characteristics. In contrast, adaptive FSGS is associated with excessive nephron workload due to increased body size, reduced nephron capacity, or single glomerular hyperfiltration associated with certain diseases. Additional etiologies are now recognized as drivers of FSGS: high-penetrance genetic FSGS due to mutations in one of nearly 40 genes, virus-associated FSGS, and medication-associated FSGS...
March 7, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28236143/c3-glomerulopathy-and-eculizumab-a-report-on-four-paediatric-cases
#11
Célia Lebreton, Justine Bacchetta, Frédérique Dijoud, Lucie Bessenay, Véronique Fremeaux-Bacchi, Anne Laure Sellier-Leclerc
BACKGROUND: Eculizumab may be used to treat C3-glomerulopathy (C3G), a rare but severe glomerular disease. DIAGNOSIS AND TREATMENT: Patients 1, 2 and 3 were diagnosed with nephritic syndrome with alternative complement pathway activation (low C3, C3Nef-positive) and C3G at the age of 9, 13 and 12 years, respectively. Treatment with eculizumab normalized proteinuria within 1, 2 and 7 months, respectively. Proteinuria relapsed when eculizumab was withdrawn, but the re-introduction of eculizumab normalized proteinuria...
February 24, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28219579/glomerular-diseases-and-renal-transplantation-pathogenic-pathways-and-evolution-of-therapeutic-interventions
#12
S Marinaki, C Skalioti, J Boletis
Glomerular diseases and renal transplantation are the main fields of nephrology in which the immune system plays a prevalent role. Glomerular diseases have traditionally been attributed to auto-immune conditions, whereas allograft rejection has been considered an allo-immune response. However, common immunopathologic mechanisms that include Toll-like receptors, complement and B-cell activation, as well as genetic and infectious factors appear to be involved in the pathogenesis of both entities. Novel therapeutic regimens directed against specific targets of the immune system show promising results in glomerulopathies as well as in renal transplantation...
March 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28207978/glomerular-c4d-deposits-can-mark-structural-capillary-wall-remodelling-in-thrombotic-microangiopathy-and-transplant-glomerulopathy-c4d-beyond-active-antibody-mediated-injury-a-retrospective-study
#13
Adil H Gasim, Jamie S Chua, Ron Wolterbeek, John Schmitz, Eric Weimer, Harsharan K Singh, Volker Nickeleit
Peritubular capillary C4d (ptc-C4d) usually marks active antibody-mediated rejection, while pseudolinear glomerular capillary C4d (GBM-C4d) is of undetermined diagnostic significance, especially when seen in isolation without concurrent ptc-C4d. We correlated GBM-C4d with structural GBM abnormalities and active antibody-mediated rejection in 319 renal transplant and 35 control native kidney biopsies. In kidney transplants, ptc-C4d was associated with GBM-C4d in 97% by immunofluorescence microscopy (IF) and 61% by immunohistochemistry (IHC; P < 0...
February 16, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28199785/assessment-of-tocilizumab-anti-il-6-receptor-monoclonal-as-a-potential-treatment-for-chronic-antibody-mediated-rejection-and-transplant-glomerulopathy-in-hla-sensitized-renal-allograft-recipients
#14
Jua Choi, Olivier Aubert, Ashley Vo, Alexandre Loupy, Mark Haas, Dechu Puliyanda, Irene Kim, Sabrina Louie, Alexis Kang, Alice Peng, Joe Kahwaji, Nancy Reinsmoen, Mieko Toyoda, Stanley C Jordan
Extending the functional integrity of renal allografts is the primary goal of transplant medicine. Development of donor-specific antibodies (DSAs) post-transplant leads to chronic active antibody-mediated rejection (cABMR) and transplant glomerulopathy (TG), resulting in the majority of graft losses in the U.S. This reduces the quality & length of life for patients and increases cost. There are no approved treatments for cABMR. Evidence suggests the pro-inflammatory cytokine interleukin 6 (IL-6) may play an important role in DSA generation and cABMR...
February 15, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28149647/hepatitis-c-and-kidney-disease-a-narrative-review
#15
REVIEW
Rashad S Barsoum, Emad A William, Soha S Khalil
Hepatitis-C (HCV) infection can induce kidney injury, mostly due to formation of immune-complexes and cryoglobulins, and possibly to a direct cytopathic effect. It may cause acute kidney injury (AKI) as a part of systemic vasculitis, and augments the risk of AKI due to other etiologies. It is responsible for mesangiocapillary or membranous glomerulonephritis, and accelerates the progression of chronic kidney disease due to other causes. HCV infection increases cardiovascular and liver-related mortality in patients on regular dialysis...
March 2017: Journal of Advanced Research
https://www.readbyqxmd.com/read/28135784/morphologic-patterns-and-treatment-of-transplant-glomerulopathy-a-retrospective-analysis
#16
Rui Abreu, Fernanda Carvalho, Helena Viana, Isabel Mesquita, Marília Possante, Inês Aires, Fernando Caeiro, Cecília Silva, Patrícia Cotovio, Aníbal Ferreira, Francisco Remédio, Fernando Nolasco
Transplant glomerulopathy is mainly due to chronic antibody-mediated rejection and actually represents a major cause of long-term allograft failure. The lack of effective treatment remains a serious problem in transplantation. A retrospective and uni-center study was performed in 48 kidney allograft recipients with transplant glomerulopathy between January 2010 and December 2015. Median time for diagnosis was 7.1 (3.6-11.8) years post-transplant. Light microscopy showed severity of transplant glomerulopathy in the majority of patients (cg1=10...
April 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28121909/urinary-metabolomics-for-noninvasive-detection-of-antibody-mediated-rejection-in-children-after-kidney-transplantation
#17
Tom D Blydt-Hansen, Atul Sharma, Ian W Gibson, David S Wishart, Rupasri Mandal, Julie Ho, Peter Nickerson, David Rush
BACKGROUND: Biomarkers are needed that identify patients with antibody-mediated rejection (ABMR). The goal of this study was to evaluate the utility of urinary metabolomics for early noninvasive detection of ABMR in pediatric kidney transplant recipients. METHODS: Urine samples (n=396) from a prospective, observational cohort of 59 renal transplant patients with surveillance or indication biopsies were assayed for 133 unique metabolites by quantitative mass spectrometry...
January 25, 2017: Transplantation
https://www.readbyqxmd.com/read/28058212/complement-related-kidney-diseases-recurrence-after-transplantation
#18
REVIEW
Maurizio Salvadori, Elisabetta Bertoni
The recurrence of renal disease after renal transplantation is becoming one of the main causes of graft loss after kidney transplantation. This principally concerns some of the original diseases as the atypical hemolytic uremic syndrome (HUS), the membranoproliferative glomerulonephritis (MPGN), in particular the MPGN now called C3 glomerulopathy. Both this groups of renal diseases are characterized by congenital (genetic) or acquired (auto-antibodies) modifications of the alternative pathway of complement...
December 24, 2016: World Journal of Transplantation
https://www.readbyqxmd.com/read/28031959/averting-the-legacy-of-kidney-disease-focus-on-childhood
#19
REVIEW
Julie R Ingelfinger, Kamyar Kalantar-Zadeh, Franz Schaefer
World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life...
June 2016: Future Science OA
https://www.readbyqxmd.com/read/27992962/c1q-binding-is-not-an-independent-risk-factor-for-kidney-allograft-loss-after-an-acute-antibody-mediated-rejection-episode-a-retrospective-cohort-study
#20
Anissa Moktefi, Juliette Parisot, Dominique Desvaux, Florence Canoui-Poitrine, Isabelle Brocheriou, Julie Peltier, Vincent Audard, Tomek Kofman, Caroline Suberbielle, Philippe Lang, Eric Rondeau, Philippe Grimbert, Marie Matignon
After kidney transplantation, C4d is an incomplete marker of acute antibody-mediated rejection (AMR) and C1q-binding donor-specific antibodies (DSA) have been associated with allograft survival. However, the impact on allograft survival of C1q+ DSA after clinical AMR has not been studied yet. We analysed retrospectively in clinical AMR C4d staining and C1q binding impact on allograft survival. We compared clinical, histological, and serological features of C4d- and C4d+ AMR, C1q+ and C1q- DSA AMR and analysed C4d and C1q-binding impact on allograft survival...
December 19, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
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