Cytomegalovirus-induced thrombotic microangiopathy after renal transplant successfully treated with eculizumab: case report and review of the literature

Java, Anuja; Edwards, Angelina; Rossi, Ana P.; Pandey, Richa; Gaut, Joseph P.; Santos, Rowena Delos; Miller, Brent W.; Klein, Christina L.; Brennan, Daniel C.

doi:10.1111/tri.12582

Cited by 34 publications

(25 citation statements)

References 23 publications

(17 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, a virus associated complement-mediated destruction of endothelial cells might be involved because CMV has been reported to cause direct activation of the classical pathway and TA-TMA is a disease closely related with abnormalities of the complement system. [3,4,16] Serum LDH concentration > 500U/L was found to be an early marker for TA-TMA occurrence, and it elevated at a median of 6 days before TA-TMA diagnosis. This finding agreed to recent literatures that LDH could be an early marker of TA-TMA, and could be included in a noninvasive laboratory diagnostic panel for the early detection and prognosis of TA-TMA.…”

Section: Discussionmentioning

confidence: 97%

Risk and prognostic factors of transplantation‐associated thrombotic microangiopathy in allogeneic haematopoietic stem cell transplantation: a nested case control study

Zheng

Wang

et al. 2016

Hematological Oncology

View full text Add to dashboard Cite

Transplantation-associated thrombotic microangiopathy (TA-TMA) is a significant complication of haematopoietic stem cell transplantation. However, it remains controversial which clinical or laboratory markers are of evident risk and prognostic value. From 2006 to 2013, a nested case control study was carried out in our centre to study the risk and prognostic factors of TA-TMA. A total of 654 consecutive patients who underwent allogeneic haematopoietic stem cell transplantation were studied. Twenty-six (4.0%) patients matched the established diagnostic criteria. Subjects with TA-TMA had significantly higher 3-year none relapse mortality compared with those without (65.4% vs 15.4%, P < 0.0001). Grades 2 to 4 aGVHD and cytomegalovirus viremia were independent risk factors, and serum LDH level >500U/L as well as hypertension were early signs of TA-TMA occurrence. Liver dysfunction and significant gastric bleeding were independent risk factors for TA-TMA related mortality. Subjects with either liver dysfunction or significant gastric bleeding had significantly higher 3 year TA-TMA related mortality cumulative incidence than subjects without. These observations lead to the conclusion that allo-HSCT recipients with grades 2 to 4 aGVHD or cytomegalovirus viremia should be monitored for TA-TMA. Liver dysfunction and significant gastric bleeding are prognostic factors for TA-TMA. Copyright © 2016 John Wiley & Sons, Ltd.

show abstract

Section: Discussionmentioning

confidence: 97%

Risk and prognostic factors of transplantation‐associated thrombotic microangiopathy in allogeneic haematopoietic stem cell transplantation: a nested case control study

Zheng

Wang

et al. 2016

Hematological Oncology

View full text Add to dashboard Cite

show abstract

“… CMV No evidence. Case report of de novo TMA after kidney transplant in the context of CMV infection, and recurrence of TMA with recurrence of CMV viraemia in the absence of CNI; successfully treated with valganciclovir and eculizumab [ 163 ]. No evidence.…”

Section: Evidence For the Role Of Complement In The Tmasmentioning

confidence: 99%

Complement C5-inhibiting therapy for the thrombotic microangiopathies: accumulating evidence, but not a panacea

Brocklebank

Kavanagh

2017

Clinical Kidney Journal

View full text Add to dashboard Cite

Thrombotic microangiopathy (TMA), characterized by organ injury occurring consequent to severe endothelial damage, can manifest in a diverse range of diseases. In complement-mediated atypical haemolytic uraemic syndrome (aHUS) a primary defect in complement, such as a mutation or autoantibody leading to over activation of the alternative pathway, predisposes to the development of disease, usually following exposure to an environmental trigger. The elucidation of the pathogenesis of aHUS resulted in the successful introduction of the complement inhibitor eculizumab into clinical practice. In other TMAs, although complement activation may be seen, its role in the pathogenesis remains to be confirmed by an interventional trial. Although many case reports in TMAs other than complement-mediated aHUS hint at efficacy, publication bias, concurrent therapies and in some cases the self-limiting nature of disease make broader interpretation difficult. In this article, we will review the evidence for the role of complement inhibition in complement-mediated aHUS and other TMAs.

show abstract

“…Eculizumab, a monoclonal antibody which prevents the production of membrane attack complex (MAC) by inhibiting conversion of C5 to C5a and C5b, has been successfully tried in the treatment of TMA secondary to calcineurin inhibitor and cytomegalovirus (CMV). Discontinuation of causative agents and early initiation of eculizumab therapy protects against further complement mediated host cell damage and also provides ample time for the treatment of infections [66, 67]. Recently, a retrospective study conducted by Arai et al demonstrated that serum levels of neutrophil extracellular traps (NETs) were significantly elevated when compared to the pretransplantation level especially in patients developing TMA following HSCT.…”

Section: Pathophysiology Of Acute Kidney Injury In Hsctmentioning

confidence: 99%

Acute Kidney Injury in Hematopoietic Stem Cell Transplantation: A Review

Krishnappa

Gupta

Manu

et al. 2016

International Journal of Nephrology

View full text Add to dashboard Cite

Hematopoietic stem cell transplantation (HSCT) is a highly effective treatment strategy for lymphoproliferative disorders and bone marrow failure states including aplastic anemia and thalassemia. However, its use has been limited by the increased treatment related complications, including acute kidney injury (AKI) with an incidence ranging from 20% to 73%. AKI after HSCT has been associated with an increased risk of mortality. The incidence of AKI reported in recipients of myeloablative allogeneic transplant is considerably higher in comparison to other subclasses mainly due to use of cyclosporine and development of graft-versus-host disease (GVHD) in allogeneic groups. Acute GVHD is by itself a major independent risk factor for the development of AKI in HSCT recipients. The other major risk factors are sepsis, nephrotoxic medications (amphotericin B, acyclovir, aminoglycosides, and cyclosporine), hepatic sinusoidal obstruction syndrome (SOS), thrombotic microangiopathy (TMA), marrow infusion toxicity, and tumor lysis syndrome. The mainstay of management of AKI in these patients is avoidance of risk factors contributing to AKI, including use of reduced intensity-conditioning regimen, close monitoring of nephrotoxic medications, and use of alternative antifungals for prophylaxis against infection. Also, early identification and effective management of sepsis, tumor lysis syndrome, marrow infusion toxicity, and hepatic SOS help in reducing the incidence of AKI in HSCT recipients.

show abstract

Cytomegalovirus-induced thrombotic microangiopathy after renal transplant successfully treated with eculizumab: case report and review of the literature

Cited by 34 publications

References 23 publications

Risk and prognostic factors of transplantation‐associated thrombotic microangiopathy in allogeneic haematopoietic stem cell transplantation: a nested case control study

Risk and prognostic factors of transplantation‐associated thrombotic microangiopathy in allogeneic haematopoietic stem cell transplantation: a nested case control study

Complement C5-inhibiting therapy for the thrombotic microangiopathies: accumulating evidence, but not a panacea

Acute Kidney Injury in Hematopoietic Stem Cell Transplantation: A Review

Contact Info

Product

Resources

About