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https://www.readbyqxmd.com/read/28306593/current-concepts-for-sensitized-patients-before-transplantation
#1
Dael Geft, Jon Kobashigawa
PURPOSE OF REVIEW: Antibody allosensitization poses a major immunologic challenge for patients awaiting heart transplantation. It is associated with significant morbidity and mortality for both pretransplant and posttransplant patients by prolonging wait times to transplant and increasing posttransplant rejection and vasculopathy. Many questions remain regarding methods and interpretation of antibody detection, the relevance of sensitization in specific patient populations such as those with mechanical circulatory support and the ideal strategies for desensitization...
March 16, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28287636/transplant-associated-thrombotic-microangiopathy-opening-pandora-s-box
#2
REVIEW
E Gavriilaki, I Sakellari, A Anagnostopoulos, R A Brodsky
Transplant-associated thrombotic microangiopathy (TA-TMA) is an early complication of hematopoietic cell transplantation (HCT). A high mortality rate is documented in patients who are refractory to calcineurin inhibitor cessation. Estimates of TA-TMA prevalence vary significantly and are higher in allogeneic compared with autologous HCT. Furthermore, our understanding of the pathophysiology that is strongly related to diagnosis and treatment options is limited. Recent evidence has linked TA-TMA with atypical hemolytic uremic syndrome, a disease of excessive activation of the alternative pathway of complement, opening the Pandora's box in treatment options...
March 13, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28236143/c3-glomerulopathy-and-eculizumab-a-report-on-four-paediatric-cases
#3
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 Proteinuria relapsed when eculizumab was withdrawn, but the re-introduction of eculizumab normalized proteinuria...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/28224376/a-case-of-atypical-hemolytic-uremic-syndrome-in-a-second-renal-transplant
#4
Nicholas A Zwang, Bing Ho, Yashpal S Kanwar, Brad Lewis, Matthew Cusick, John J Friedewald, Lorenzo Gallon
Atypical hemolytic uremic syndrome (aHUS) has gained increased visibility over several years as an important cause of renal failure. Unfortunately, diagnosis is often difficult because individual courses can be highly variable depending the causative genetic mutations. Here we present the case of a patient with a failed renal allograft and acute failure of a second allograft who was ultimately diagnosed with aHUS. Interestingly, he developed early de novo donor specific antibodies (DSA) after the second renal transplant in context of likely recurrent aHUS...
February 21, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28176480/de-novo-thrombotic-microangiopathy-following-simultaneous-pancreas-and-kidney-transplantation-managed-with-eculizumab
#5
REVIEW
Lani Shochet, John Kanellis, Ian Simpson, Joseph Ta, William Mulley
Thrombotic microangiopathy (TMA) is a well-recognised complication following transplantation, often due to an underlying genetic predisposition, medications or rejection. The use of eculizumab in these settings has been previously described, but its role still remains to be clarified. A 45-year-old man, with a history of type 1 diabetes mellitus and subsequent end-stage kidney failure, presented for a simultaneous pancreas-kidney transplant. Immunologically, he was well matched with the donor, and he received standard induction immunosuppression including tacrolimus...
February 2017: Nephrology
https://www.readbyqxmd.com/read/28176477/absence-of-thrombocytopaenia-and-or-microangiopathic-haemolytic-anaemia-does-not-reliably-exclude-recurrence-of-atypical-haemolytic-uraemic-syndrome-after-kidney-transplantation
#6
REVIEW
Anoushka R Krishnan, Brian Siva, Aron Chakera, Germaine Wong, Daniel Wong, Wai H Lim
A 54-year-old man was diagnosed with atypical haemolytic uraemic syndrome (aHUS) with confirmed complement H mutation in 2012, requiring ongoing dialysis. He was commenced on eculizumab in 2014 once the pharmaceutical board approved this drug. After 4 months, he received a live unrelated donor renal transplant from his wife and continued eculizumab post-transplant. Three months later, there was a rise in his creatinine with no laboratory features of haemolysis and a kidney biopsy confirmed rejection, which was treated with increased immunosuppression...
February 2017: Nephrology
https://www.readbyqxmd.com/read/28141920/face-transplantation-partial-graft-loss-of-the-first-case-10-years-later
#7
E Morelon, P Petruzzo, J Kanitakis, S Dakpé, O Thaunat, V Dubois, G Choukroun, S Testelin, J-M Dubernard, L Badet, B Devauchelle
Ten years after the first face transplantation, we report the partial loss of this graft. After two episodes of acute rejection (AR) occurred and completely reversed in the first posttransplantation year, at 90 months posttransplantation the patient developed de novo class II donor-specific antibodies, without clinical signs of AR. Some months later, she developed several skin rejection episodes treated with steroid pulses. Despite rapid clinical improvement, some months later the sentinel skin graft underwent necrosis...
January 31, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28104134/eculizumab-and-belatacept-for-de-novo-atypical-hemolytic-uremic-syndrome-associated-with-cfhr3-cfhr1-deletion-in-a-kidney-transplant-recipient-a-case-report
#8
P Dedhia, A Govil, G Mogilishetty, R R Alloway, E S Woodle, B G Abu Jawdeh
BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is associated with significant morbidity and mortality and occurs due to genetic or acquired abnormalities that result in the dysregulation of the alternative complement pathway. CASE REPORT: We report a case of post-living kidney transplantation de novo aHUS in a setting of heterozygous deletion in the complement factor H-related protein (CFHR)3-CFHR1 gene. The aHUS episode was possibly triggered by antibody-mediated rejection or tacrolimus...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28104125/efficacy-of-eculizumab-therapy-for-atypical-hemolytic-uremic-syndrome-recurrence-and-antibody-mediated-rejection-progress-after-renal-transplantation-with-preformed-donor-specific-antibodies-case-report
#9
T Yamamoto, Y Watarai, K Futamura, M Okada, M Tsujita, T Hiramitsu, N Goto, S Narumi, A Takeda, T Kobayashi
Atypical hemolytic uremic syndrome (aHUS) develops as the result of unregulated complement progression and precipitates de novo thrombotic microangiopathy. Plasma therapy is used to control the progression of the complement cascade, but that therapy is not effective in all patients and is accompanied by risk of infection and/or allergy. Eculizumab has been reported as an efficient therapy for aHUS. We report the case of a 35-year old woman who underwent effective eculizumab therapy for aHUS recurrence and antibody-mediated rejection (AMR) progress after renal transplantation with preformed donor-specific antibodies (DSA)...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28058212/complement-related-kidney-diseases-recurrence-after-transplantation
#10
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/27990486/successful-simultaneous-liver-kidney-transplantation-in-the-presence-of-multiple-high-titered-class-i-and-ii-antidonor-hla-antibodies
#11
Flavio Paterno, Alin Girnita, Paul Brailey, David Witte, Jiang Wang, Madison C Cuffy, Tayyab Diwan, Simon Tremblay, Jane Y Revollo, Rita R Alloway, Michael R Schoech, Nadim Anwar, Shimul A Shah, Steve E Woodle
The results of simultaneous liver-kidney transplants in highly sensitized recipients have been controversial in terms of antibody-mediated rejection and kidney allograft outcomes. This case report provides a detailed and sophisticated documentation of histocompatibility and pathologic data in a simultaneous liver-kidney transplant performed in a recipient with multiple high-titered class I and II antidonor HLA antibodies and a strongly positive cytotoxic crossmatch. Patient received induction with steroids, rituximab, and eculizumab without lymphocyte depleting agents...
December 2016: Transplantation Direct
https://www.readbyqxmd.com/read/27974406/thrombotic-microangiopathy-in-inverted-formin-2-mediated-renal-disease
#12
Rachel C Challis, Troels Ring, Yaobo Xu, Edwin K S Wong, Oliver Flossmann, Ian S D Roberts, Saeed Ahmed, Michael Wetherall, Giedrius Salkus, Vicky Brocklebank, Julian Fester, Lisa Strain, Valerie Wilson, Katrina M Wood, Kevin J Marchbank, Mauro Santibanez-Koref, Timothy H J Goodship, David Kavanagh
The demonstration of impaired C regulation in the thrombotic microangiopathy (TMA) atypical hemolytic uremic syndrome (aHUS) resulted in the successful introduction of the C inhibitor eculizumab into clinical practice. C abnormalities account for approximately 50% of aHUS cases; however, mutations in the non-C gene diacylglycerol kinase-ε have been described recently in individuals not responsive to eculizumab. We report here a family in which the proposita presented with aHUS but did not respond to eculizumab...
December 14, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27932157/belatacept-and-eculizumab-for-treatment-of-calcineurin-inhibitor-induced-thrombotic-microangiopathy-after-kidney-transplantation-case-report
#13
J Merola, P S Yoo, J Schaub, J D Smith, M I Rodriguez-Davalos, E Tichy, D C Mulligan, W Asch, R Formica, M Kashgarian, S Kulkarni
Thrombotic microangiopathy (TMA) after kidney transplantation is an uncommon and challenging cause of graft dysfunction and is associated with early graft loss. An idiosyncratic endothelial reaction to calcineurin inhibitors (CNIs) has been implicated as a frequent cause of TMA. This reaction is marked by uncontrolled activation of complement and subsequent cellular destruction. Usual therapy consists of withdrawal of the inciting drug and plasmapheresis to minimize levels of circulating complement. Recently, eculizumab, a monoclonal antibody to complement component C5, has been used for the treatment of atypical hemolytic uremic syndrome...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27932156/dosing-eculizumab-for-antibody-mediated-rejection-in-kidney-transplantation-a-case-report
#14
B Smith, V Kumar, D Mompoint-Williams, R D Reed, P A MacLennan, K Stegner, J E Locke
Severe antibody-mediated rejection (AMR) of a blood type-incompatible (ABOi) living donor kidney transplantation (LDKT) can lead to graft failure, and aggressive therapies, such as the anticomplement antibody eculizumab, are often used to rescue the affected graft. Eculizumab therapy can be crippling financially. Current literature suggests a wide variation in the amount and timing of eculizumab given as rescue therapy in the setting of AMR. Herein we describe a limited-eculizumab regimen in the setting of severe AMR that is both clinically and cost effective...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27871301/an-innovative-and-collaborative-partnership-between-patients-with-rare-disease-and-industry-supported-registries-the-global-ahus-registry
#15
REVIEW
Len Woodward, Sally Johnson, Johan Vande Walle, Joran Beck, Christoph Gasteyger, Christoph Licht, Gema Ariceta
BACKGROUND: Patients are becoming increasingly involved in research which can promote innovation through novel ideas, support patient-centred actions, and facilitate drug development. For rare diseases, registries that collect data from patients can increase knowledge of the disease's natural history, evaluate clinical therapies, monitor drug safety, and measure quality of care. The active participation of patients is expected to optimise rare-disease management and improve patient outcomes...
November 21, 2016: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/27848226/atypical-hemolytic-uremic-syndrome-in-the-setting-of-complement-amplifying-conditions-case-reports-and-a-review-of-the-evidence-for-treatment-with-eculizumab
#16
REVIEW
Arif Asif, Ali Nayer, Christian S Haas
Atypical hemolytic uremic syndrome (aHUS) is a rare, genetic, progressive, life-threatening form of thrombotic microangiopathy (TMA) predominantly caused by dysregulation of the alternative pathway of the complement system. Complement-amplifying conditions (CACs), including pregnancy complications [preeclampsia, HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome], malignant hypertension, autoimmune diseases, transplantation, and others, are associated with the onset of TMA in up to 69 % of cases of aHUS...
November 15, 2016: Journal of Nephrology
https://www.readbyqxmd.com/read/27775697/is-complement-blockade-an-acceptable-therapeutic-strategy-for-hematopoietic-cell-transplant-associated-thrombotic-microangiopathy
#17
REVIEW
P Dhakal, V R Bhatt
Diagnosis and management of hematopoietic cell transplant-associated thrombotic microangiopathy (TA-TMA) are very complex and controversial, given multiple ongoing issues and comorbidities in sick transplant recipients. Complement activation via classic and alternative pathways is emerging as a potential pathogenetic mechanism in the development of TA-TMA. Complement-centric diagnostic strategy using functional and genetic tests may possibly support diagnosis, enhance molecular understanding and direct drug development...
March 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/27768015/hemolytic-uremic-syndrome-in-children
#18
Valentina Talarico, Monica Aloe, Alice Monzani, Roberto Miniero, Gianni Bona
Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy defined by thrombocytopenia, non-immune microangiopathic hemolytic anemia and acute renal failure. HUS is typically classified into two primary types: 1) HUS due to infections, often associated with diarrhea (D+HUS, Shiga toxin-producing Escherichia Coli-HUS), with the rare exception of HUS due to a severe disseminated infection caused by Streptococcus; 2) HUS related to complement, such HUS is also known as "atypical HUS" and is not diarrhea associated (D-HUS, aHUS); but recent studies have shown other forms of HUS, that can occur in the course of systemic diseases or physiopathological conditions such as pregnancy, after transplantation or after drug assumption...
December 2016: Minerva Pediatrica
https://www.readbyqxmd.com/read/27766045/clinical-evaluation-of-thrombotic-microangiopathy-identification-of-patients-with-suspected-atypical-hemolytic-uremic-syndrome
#19
REVIEW
Yu-Min Shen
Atypical hemolytic uremic syndrome (aHUS) is a rare genetic disorder caused by defective complement regulation resulting in thrombotic microangiopathy (TMA). Patients can present as children or adults. The syndrome consists of hemolytic anemia with schistocytosis, thrombocytopenia, significant renal damage, and/or other organ system dysfunction(s). Patients with aHUS may succumb to the complications of the disease with the very first manifestation; surviving patients often suffer from progressive organ dysfunction with significant morbidity and mortality despite plasma infusion or plasma exchange...
2016: Thrombosis Journal
https://www.readbyqxmd.com/read/27744619/long-term-successful-liver-kidney-transplantation-in-a-child-with-atypical-hemolytic-uremic-syndrome-caused-by-homozygous-factor-h-deficiency
#20
Emmanuel Gonzales, Tim Ulinski, Dalila Habes, Georges Deschênes, Véronique Frémeaux-Bacchi, Albert Bensman
BACKGROUND: Rational options for the treatment of end-stage renal disease (ESRD) due to atypical hemolytic uremic syndrome (aHUS) in children are still open to discussion. In the case of human complement factor H (CFH) deficiency, the choice is either kidney transplantation in combination with eculizumab, a humanized anti-C5 monoclonal antibody, or a combined liver-kidney transplantation. CASE-DIAGNOSIS/TREATMENT: A child with a homozygous CFH deficiency underwent a successful liver-kidney transplantation...
December 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
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