Eculizumab for the Treatment of De Novo Thrombotic Microangiopathy Post Simultaneous Pancreas-Kidney Transplantation—A Case Report

Chandran, Sindhu; Baxter‐Lowe, Lee Ann; Olson, Jean L.; Tomlanovich, Stephen J.; Webber, Allison B.

doi:10.1016/j.transproceed.2011.02.064

Cited by 48 publications

(29 citation statements)

References 17 publications

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“…13 A review of published reports 65 demonstrates the use of eculizumab in a total of 26 cases of TA-TMA following HSCT or solid organ transplant. 9,13,[66][67][68][69][70][71][72][73][74][75] The cases were initially treated with discontinuation or dose reduction in CNI with or without plasma exchange. Of these patients, 24 (92%) were alive at 1-year follow-up, 65 and the remaining 2 (8%) pediatric patients did not achieve therapeutic levels even after dose escalation and died.…”

Section: Managementmentioning

confidence: 99%

Hematopoietic Stem Cell Transplant-Associated Thrombotic Microangiopathy

Elsallabi

Bhatt

Dhakal

et al. 2015

Clin Appl Thromb Hemost

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Hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA) is a fatal, multifactorial disorder, which may present with thrombocytopenia, hemolysis, acute renal failure, mental status changes and involvement of other organs. The pathogenesis of TA-TMA is complex and includes multiple risk factors such as certain conditioning regimens, calcineurin inhibitors (CNIs), graft-versus-host disease (GVHD), human leukocyte antigen mismatch, and opportunistic infections. The end result of these insults is endothelial injury in the kidney and other organs. Recent studies also indicate a role of complement activation in tissue damage. The lack of sensitive and specific diagnostic tests for TA-TMA often results in delayed diagnosis. Biopsy is not always possible for diagnosis because of the risk of complications such as bleeding. Recently, an emerging role of renal-centered screening approach has been demonstrated, which utilize the monitoring of blood pressure, urine protein, serum lactate dehydrogenase and hemogram for early detection. Therapeutic options are limited, and plasma exchange plays a minor role. Withdrawal of offending agent such as CNIs and the use of rituximab can be effective in some patients. However, the current treatment strategy is suboptimal and associated with high mortality rate. Recently, eculizumab has been utilized in a few patients with good outcomes. Patients, who develop TA-TMA, are also at an increased risk of GVHD, infection, renal, cardiovascular, and other complications, which can contribute to high mortality. Better understanding of molecular pathogenesis, improvement in posttransplant management, leading to early diagnosis, and management of TA-TMA are required to improve outcomes of this fatal entity.

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Section: Managementmentioning

confidence: 99%

Hematopoietic Stem Cell Transplant-Associated Thrombotic Microangiopathy

Elsallabi

Bhatt

Dhakal

et al. 2015

Clin Appl Thromb Hemost

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“…Plasma exchange in addition to CNI withdrawal can contribute to graft salvage (71,73,84). Recently, cases of remission with eculizumab in post-transplant de novo TMA in transplant have been reported (85)(86)(87).…”

Section: Thrombotic Microangiopathymentioning

confidence: 99%

De Novo Glomerular Diseases after Renal Transplantation

Ponticelli

Moroni

Glassock

2014

Clinical Journal of the American Society of Nephrology

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Glomerular diseases developing in the kidney allograft are more often recurrences of the original disease affecting the native kidneys. However, in an undefined number of cases de novo, glomerular diseases unrelated to the original disease in the native kidneys can develop in the transplanted kidney. The clinical presentation and histologic features of de novo diseases are often similar to those features observed in patients with primary or secondary GN in the native kidneys. However, in transplanted kidneys, the glomerular, vascular, and tubulointerstitial changes are often intertwined with structural abnormalities already present at the time of transplant or caused by antibody-or cell-mediated allograft rejection, immunosuppressive drugs, or superimposed infection (most often of a viral nature). The pathophysiology of de novo glomerular diseases is quite variable. In rare cases of de novo minimal change disease, circulating factors increasing the glomerular permeability likely participate. Maladaptive hemodynamic changes and tissue fibrosis caused by calcineurin inhibitors or other factors may be involved in the pathogenesis of de novo FSGS. The exposure of cryptic podocyte antigens may favor the development of de novo membranous nephropathy. Many cases of de novo membranoproliferative GN are related to hepatitis C virus infection. Patients with Alport syndrome lacking antigenic epitopes in their glomerular basement membrane may develop antibodies against these glomerular basement membrane antigens expressed in the transplanted kidney. Infection may cause acute GN to have a heterogeneous clinical presentation and outcome. De novo pauci-immune GN in renal transplant is rare. Preexisting or acquired intolerance to glucose may, in the long term, cause diabetic nephropathy. The prognosis of de novo diseases depends on the type of GN, the severity of lesions caused by the alloimmune response, or the efficacy of immunosuppressive therapy. In most cases, the management of de novo glomerular diseases is empirical or elusive.

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“…Both the findings of Le Quintrec et al [8] and the observation that this patient presented with apparent de novo post-transplant TMA raise the possibility that de novo post-transplant TMA should be treated with eculizumab especially if it is resistant to plasma exchange. There are anecdotal reports supporting this [10,11]. Future transplantation in this patient will undoubtedly need to be undertaken under the cover of eculizumab.…”

Section: Discussionmentioning

confidence: 84%

Prevalence in the General Population of a CFH Sequence Variant Associated with Atypical Haemolytic Uraemic Syndrome in an Extensive Family from Southwest England

et al. 2013

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Background/Aims: Twenty-five members of a family from the county of Devon in England have been affected by atypical haemolytic uraemic syndrome (aHUS) associated with a CFH mutation (c.3643C>G; p.Arg1215Gly). A 65-year-old male was diagnosed with aHUS after losing a renal transplant to a thrombotic microangiopathy. Subsequent mutation screening revealed the same CFH mutation without him being knowingly related to the local kindred. We designed a study to investigate the prevalence of this mutation in the local area. In addition, we examined the diagnoses of pre-existing haemodialysis patients to determine whether other patients might unknowingly be at risk of carrying the same CFH mutation. Methods: The Exeter Ten Thousand (EXTEND) study aims to recruit 10,000 healthy volunteers over the age of 18 years living within 25 miles of Exeter in Devon. We genotyped DNA from 4,000 EXTEND subjects for CFH c.3643C>G; p.Arg1215Gly. We reviewed the diagnoses of 294 haemodialysis patients in the Devon area and genotyped 7 patients with either end-stage renal disease of unknown aetiology, malignant hypertension or renovascular disease. Results: CFH c.3643C>G; p.Arg1215Gly was not detected in any of the 7 haemodialysis patients or the 4,000 individuals within the EXTEND study. Conclusions: We conclude that CFH c.3643C>G; p.Arg1215Gly is not endemic in Devon. This reinforces our existing practice of genotyping only patients with kidney disease and evidence of a thrombotic microangiopathy for this mutation. This is the first study looking at the prevalence of CFH mutations in the general population.

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Eculizumab for the Treatment of De Novo Thrombotic Microangiopathy Post Simultaneous Pancreas-Kidney Transplantation—A Case Report

Cited by 48 publications

References 17 publications

Hematopoietic Stem Cell Transplant-Associated Thrombotic Microangiopathy

Hematopoietic Stem Cell Transplant-Associated Thrombotic Microangiopathy

De Novo Glomerular Diseases after Renal Transplantation

Prevalence in the General Population of a CFH Sequence Variant Associated with Atypical Haemolytic Uraemic Syndrome in an Extensive Family from Southwest England

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