Pharmacologic Complement Inhibition in Clinical Transplantation

AbstractPurpose of ReviewOver the past two decades, significant strides made in our understanding of the etiology of antibody-mediated rejection (AMR) in transplantation have put the complement system in the spotlight. Here, we review recent progress made in the field of pharmacologic complement inhibition in clinical transplantation and aim to understand the impact of this therapeutic approach on outcomes in transplant recipients.Recent FindingsEncouraged by the success of agents targeting the complement cascade in disorders of unrestrained complement activation like paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), investigators are testing the safety and efficacy of pharmacologic complement blockade in mitigating allograft injury in conditions ranging from AMR to recurrent post-transplant aHUS, C3 glomerulopathies and antiphospholipid anti-body syndrome (APS). A recent prospective study demonstrated the efficacy of terminal complement inhibition with eculizumab in the prevention of acute AMR in human leukocyte antigen (HLA)-incompatible living donor renal transplant recipients. C1 esterase inhibitor (C1-INH) was well tolerated in two recent studies in the treatment of AMR and was associated with improved renal allograft function.SummaryPharmacologic complement inhibition is emerging as valuable therapeutic tool, especially in the management of highly sensitized renal transplant recipients. Novel and promising agents that target variou...
Source: Current Transplantation Reports - Category: Transplant Surgery Source Type: research

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Publication date: September 2019Source: Advances in Chronic Kidney Disease, Volume 26, Issue 5Author(s): Elizabeth S. Kotzen, Sanjeet Roy, Koyal JainAntiphospholipid syndrome (APS) and other causes of thrombotic microangiopathy (TMA) negatively impact the renal outcomes of patients with systemic lupus erythematosus (SLE) and lupus nephritis. Here we review the diagnosis and management of occlusive renal vascular lesions due to APS and other TMAs, with a focus on patients with SLE and lupus nephritis. The presence of a thrombotic event, unexplained hypertension, thrombocytopenia, or hemolytic anemia should prompt considerat...
Source: Advances in Chronic Kidney Disease - Category: Urology & Nephrology Source Type: research
In this clinical vignette, we present a case of a 59-year-old woman with catastrophic antiphospholipid syndrome likely triggered by polymicrobial sepsis. The diagnostic criteria and clinical manifestations of catastrophic antiphospholipid syndrome are reviewed. We also compare diagnostic criteria and clinical manifestations with other clinical entities in the differential diagnosis, including thrombotic thrombocytopenic purpura-hemolytic-uremic syndrome, disseminated intravascular coagulation, sepsis, and inflammatory bowel disease. Catastrophic antiphospholipid syndrome is a rare, but lethal condition, and treatment recom...
Source: Current Awareness Service for Health (CASH) - Category: Consumer Health News Source Type: news
​BY GREGORY M. TAYLOR, DO, &DAWN ZELENKA-JOSHOWITZ, DOAn 81-year-old woman with a past medical history of atrial fibrillation, three coronary artery bypass graft surgeries, and a prior cerebrovascular accident presented to the emergency department with right arm pain. Her symptoms had grown worse for two days, and she experienced paralysis about two hours before arrival.Her initial vital signs were a temperature of 97.7°F, a blood pressure of 196/43 mm Hg (left arm), a heart rate of 60 bpm, and a respiratory rate of 18 bpm. She had obvious pallor to her right upper arm with no brachial or radial pulses. She was u...
Source: The Case Files - Category: Emergency Medicine Tags: Blog Posts Source Type: research
Abstract BACKGROUND: HELLP syndrome is a disorder associated with serious maternal morbidity and mortality. Distinguishing HELLP from other pregnancy related disorders is often challenging and may result in delay of treatment. Differential diagnoses include acute fatty liver of pregnancy, thrombotic thrombocytopenic purpura, antiphospholipid syndrome, and hemolytic uremic syndrome, and are reviewed in this chapter. While there is not any current treatment for HELLP, the mainstay of treatment involves maternal stabilization and timely delivery. Various treatment strategies have been attempted to help decrease the m...
Source: Current Pharmaceutical Biotechnology - Category: Biotechnology Authors: Tags: Curr Pharm Biotechnol Source Type: research
We present one case of HUS caused by adenovirus in a boy of 1 year and 7 months old with severe evolution, which required peritoneal dialysis.Diagnose:Stool sample repeated examination for adenovirus antigen was positive in 2 samples.Intervention:During hospitalization, the patient required 8 peritoneal dialysis sessions.Outcome:The renal function was corrected on discharge, the patient required cardiovascular monitoring 1 month after discharge.Lesson:Although the most common cause that leads to HUS remains STEC, other etiologies like viral ones that may be responsible for severe enteric infection with progression into HUS...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
This study describes a successful case of use of eculizumab in a patient with SLE and TMA refractory to standard therapy, and provides a literature review. Case description and search in PubMed and MEDLINE using systemic lupus erythemathous and/or antiphospholipid syndrome (APS) and eculizumab retrieved 15 case reports. Eighteen-year-old female presented acute renal failure and TMA and was diagnosed with SLE. Steroids and IV cyclophosphamide were started together with plasma exchange. After 55  days, she still persisted with microangiopathic anemia, thrombocytopenia, and anuria, and eculizumab was introduced. She had ...
Source: Clinical Rheumatology - Category: Rheumatology Source Type: research
Source: Nephrology Dialysis Transplantation - Category: Urology & Nephrology Authors: Tags: GENETIC DISEASES AND MOLECULAR GENETICS Source Type: research
CONCLUSION: Overall, the data indicate that in patients with APS and recurrent venous thrombosis, there are increased levels of FH autoantibodies, a finding associated with poor clinical outcome. PMID: 26276971 [PubMed - as supplied by publisher]
Source: Journal of Rheumatology - Category: Rheumatology Tags: J Rheumatol Source Type: research
Publication date: June 2015 Source:European Journal of Obstetrics & Gynecology and Reproductive Biology, Volume 189 Author(s): O. Pourrat , R. Coudroy , F. Pierre Pre-eclampsia complicated by severe HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome is a multi-organ disease, and can be difficult to differentiate from thrombotic microangiopathy (appearing as thrombotic thrombocytopenic purpura or hemolytic uremic syndrome), acute fatty liver, systemic erythematous lupus, antiphospholipid syndrome and severe sepsis. Many papers have highlighted the risks of misdiagnosis resulting in severe conseq...
Source: European Journal of Obstetrics and Gynecology and Reproductive Biology - Category: OBGYN Source Type: research
This article aims to review the main diseases included in the differential diagnosis of CAPS in the context of other thrombotic microangiopathies.
Source: Current Rheumatology Reports - Category: Rheumatology Source Type: research
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