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Eculizumab transplant

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...
October 24, 2016: Bone Marrow Transplantation
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
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
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...
October 15, 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Joseph Rosenthal
Transplant-associated thrombotic microangiopathy (TA-TMA) is a multifactorial disorder caused by systemic vascular endothelial injury that can be triggered by several mechanisms during the transplant process. Thrombotic microangiopathy may affect multiple systems and occurs in ~30% of patients undergoing hematopoietic stem cell transplantation. A subgroup of patients with thrombotic microangiopathy develop TA-TMA, and the other may develop other thrombotic microangiopathic disorders such as thrombotic thrombocytopenic purpura, a condition with similar finding but different pathophysiology involving ADAMTS-13...
2016: Journal of Blood Medicine
Amy Riddell, Tim Goodship, Coralie Bingham
Eculizumab, a terminal complement inhibitor, has recently been used successfully to both prevent and treat the recurrence of atypical hemolytic uremic syndrome (aHUS) post renal transplantation. We describe a case that highlights the need to monitor the effects of eculizumab on the complement system and in this case alter the dosage. Despite taking the standard recommended dose of eculizumab for an adult, this aHUS patient developed a low-grade thrombotic microangiopathy on biopsy within months of renal transplantation...
October 2016: Clinical Nephrology
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
Laura J Wozniak, Bita V Naini, Michelle J Hickey, Sarathi Bhattacharyya, Elaine F Reed, Ronald W Busuttil, Douglas G Farmer, Jorge H Vargas, Robert S Venick, Sue V McDiarmid
Acute AMR is well reported following ABO-incompatible LTx. However, it remains uncommon in ABO-compatible LTx. It typically presents with graft dysfunction ≤2 weeks post-LTx and is often associated with graft loss. We report the clinical presentation, treatment regimen, and outcome of six pediatric LTx recipients diagnosed with early acute AMR based on (i) clinical signs of graft dysfunction, (ii) histopathology indicative of acute injury ± C4d staining, and (iii) presence of HLA DSA. All patients developed elevated ALT and GGT ≤ 45 days post-LTx...
September 5, 2016: Pediatric Transplantation
Stephan Kemmner, Mareike Verbeek, Uwe Heemann
Acute kidney injury and long-term renal dysfunction are common problems following bone morrow transplantation (BMT) and highly related to mortality. The frequency and risk of renal dysfunction are directly related to the method of BMT, with myeloablative allogeneic BMT being associated to the highest risk followed by non-myeloablative allogeneic and myeloablative autologous BMT. The type of BMT is, thus, more important than co-factors such as advanced age, comorbidities, or high baseline serum creatinine. The causes for renal failure are multiple and include chemotherapy and high-dose radiation with fluid loss by diarrhea or vomiting, sepsis or nephrotoxic drugs such as calcineurin inhibitors and antimicrobials...
September 2, 2016: Journal of Nephrology
S Kulkarni, N C Kirkiles-Smith, Y H Deng, R N Formica, G Moeckel, V Broecker, L Bow, R Tomlin, J S Pober
We hypothesized that de novo donor-specific antibody (DSA) causes complement-dependent endothelial cell injury in kidney transplants, as assessed by expression of endothelial cell-associated transcripts (ENDATs), that may be attenuated through complement inhibition. In total, 15 participants (five control, 10 treatment) with DSA and deteriorating renal function were enrolled. The treatment group received 6 mo of eculizumab followed by 6 mo of observation, whereas controls were observed. The primary end point was percentage change in estimated GFR (eGFR) trajectory over the treatment period...
August 8, 2016: American Journal of Transplantation
Duy Tran, Anne Boucher, Suzon Collette, Alexis Payette, Virginie Royal, Lynne Senécal
In renal transplantation, treatment options for antibody-mediated rejection are limited. Here, we report a case of severe AMR treated with eculizumab. A 50-year-old woman known for end stage kidney disease secondary to IgA nephropathy received a kidney transplant from a 50-year-old deceased donor. At 5 months after transplantation, she presented with acute graft dysfunction and biopsy showed a severe antibody-mediated rejection associated with thrombotic microangiopathy. Despite an aggressive conventional immunosuppressive regimen, signs of rejection persisted and the patient was treated with 3 doses of eculizumab...
2016: Case Reports in Transplantation
Philip T Thrush, Elfriede Pahl, David C Naftel, Elizabeth Pruitt, Melanie D Everitt, Heather Missler, Steven Zangwill, Michael Burch, Timothy M Hoffman, Ryan Butts, William T Mahle
BACKGROUND: Current knowledge of antibody-mediated rejection (AMR) after heart transplantation (HT) stems largely from adult data. Using the Pediatric Heart Transplant Study (PHTS) database, we report the incidence of AMR, describe treatment, and evaluate outcomes for treated AMR in children after HT. METHODS: We queried the PHTS database for patients <18 years of age undergoing primary HT between January 2010 and December 2014. An AMR episode was defined as either a biopsy consistent with pathologic AMR or a rejection event based on immunotherapy augmentation directed against antibody production...
June 24, 2016: Journal of Heart and Lung Transplantation
R Anders, M Grohmann, T H Lindner, C Bergmann, J Halbritter
We report on the case of a 32-year-old female patient who initially presented with oliguric acute renal failure, hemolytic anemia with moderate thrombocytopenia and subsequently developed a transient ischemic attack in the cerebellum. The kidney biopsy revealed clinically suspected atypical hemolytic-uremic syndrome (aHUS), which was confirmed by intraglomerular thrombotic microangiopathy (TMA). Treatment with plasmapheresis and sustained administration of the C5 inhibitor eculizumab resulted in hematological remission but without improvement of kidney function...
June 29, 2016: Der Internist
Esther Benamu, José G Montoya
PURPOSE OF REVIEW: Eculizumab inhibits complement effector functions and has significantly impacted the treatment of paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. However, the risks of potentially life-threatening infections, notably with Neisseria spp. in addition to its cost, are major challenges in clinical practice. In this review, we characterize and summarize the infectious complications reported with the use of eculizumab in the context of its typical and expanding indications...
August 2016: Current Opinion in Infectious Diseases
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
S C Jordan, J Choi, J Kahwaji, A Vo
The presence of HLA antibodies remains a significant and often impenetrable barrier to kidney transplantation, leading to increased morbidity and mortality for patients remaining on long-term dialysis. In recent years, a number of new approaches have been developed to overcome these barriers. Intravenous immunoglobulin (IVIG) remains the lynchpin of HLA desensitization therapy and has been shown in a prospective, randomized, placebo-controlled trial to improve transplantation rates. In addition, IVIG used in low doses with plasma exchange is a reliable protocol for desensitization...
April 2016: Transplantation Proceedings
Ze-Jia Sun, Xin Du, Lu-Lu Su, Xiao-Dong Zhang, Yong Wang, Liang Ren, Wei Wang
No abstract text is available yet for this article.
June 5, 2016: Chinese Medical Journal
Patrick G Dean, Walter D Park, Lynn D Cornell, Carrie A Schinstock, Mark D Stegall
The aim of this study was to investigate correlations between early subclinical findings (10- and 90-day histology and gene expression data) and late outcomes (transplant glomerulopathy and graft loss) in positive crossmatch kidney transplants (+XMKTx). We compared 34 +XMKTx (19 receiving eculizumab and 15 receiving standard of care without eculizumab) to 13 -XMKTx (between August 2001 and August 2011). At 10 days, light microscopy identified subclinical inflammation in only 18% of +XMKTx, while intragraft gene expression identified inflammation in 79% (gene sets for activated macrophages, dendritic cells, NK cells or T cells)...
August 2016: Clinical Transplantation
B J Orandi, B E Lonze, A Jackson, S Terezakis, E S Kraus, N Alachkar, S M Bagnasco, D L Segev, J B Orens, R A Montgomery
Patients requiring desensitization prior to renal transplantation are at risk for developing severe antibody-mediated rejection (AMR) refractory to treatment with plasmapheresis and intravenous immunoglobulin (PP/IVIg). We have previously reported success at graft salvage, long-term graft survival and protection against transplant glomerulopathy with the use of eculizumab and splenectomy in addition to PP/IVIg. Splenectomy may be an important component of this combination therapy and is itself associated with a marked reduction in donor-specific antibody (DSA) production...
May 23, 2016: American Journal of Transplantation
Anil Chandraker, Ramon Arscott, George Murphy, Christine Lian, Ericka Bueno, Francisco Marty, Helmut Rennke, Edgar Milford, Stefan Tullius, Bodhan Pomahac
Face transplantation was performed in a highly sensitized recipient with positive preoperative crossmatch and subsequent antibody-mediated rejection. The recipient was a 45-year-old female with extensive conventional reconstructions after chemical burns over the majority of the body. Residual quality of life and facial functions were poor. Levels of circulating anti-human leukocyte antigen (HLA) antibodies were high, and panel reactive antibody score was 98%. A potential donor was identified; however, with positive T and B cell flow crossmatches...
May 2016: Military Medicine
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