Clinical Grand Rounds: Atypical Hemolytic Uremic Syndrome

Hodgkins, Kavita S.; Bobrowski, Amy E.; Lane, Jerome C.; Langman, Craig B.

doi:10.1159/000337954

Cited by 24 publications

(17 citation statements)

References 54 publications

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“…Most of the 17 patients treated for post-transplant recurrence outside of prospective trials were adults who carried high-risk mutations and/or had lost prior grafts due to recurrence [71,73,[94][95][96]. Shorter interval between the onset of recurrence and treatment initiation was correlated with greater gain of graft function [71].…”

Section: Case Reports Of Eculizumab To Treat or Prevent Post-transplamentioning

confidence: 99%

An international consensus approach to the management of atypical hemolytic uremic syndrome in children

et al. 2015

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Atypical hemolytic uremic syndrome (aHUS) emerged during the last decade as a disease largely of complement dysregulation. This advance facilitated the development of novel, rational treatment options targeting terminal complement activation, e.g., using an anti-C5 antibody (eculizumab). We review treatment and patient management issues related to this therapeutic approach. We present consensus clinical practice recommendations generated by HUS International, an international expert group of clinicians and basic scientists with a focused interest in HUS. We aim to address the following questions of high relevance to daily clinical practice: Which complement investigations should be done and when? What is the importance of anti-factor H antibody detection? Who should be treated with eculizumab? Is plasma exchange therapy still needed? When should eculizumab therapy be initiated? How and when should complement blockade be monitored? Can the approved treatment schedule be modified? What approach should be taken to kidney and/or combined liver-kidney transplantation? How should we limit the risk of meningococcal infection under complement blockade therapy? A pressing question today regards the treatment duration. We discuss the need for prospective studies to establish evidence-based criteria for the continuation or cessation of anticomplement therapy in patients with and without identified complement mutations.

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Section: Case Reports Of Eculizumab To Treat or Prevent Post-transplamentioning

confidence: 99%

An international consensus approach to the management of atypical hemolytic uremic syndrome in children

et al. 2015

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“…A randomized controlled clinical trial of eculizumab in 37 adults with aHUS showed resolution of TMA, thrombocytopenia, and return of kidney function [9]. As supported by this case report, eculizumab appears to be especially effective in recurrent TMA post-transplant [5, 10, 11]. Treatment with C5 inhibition may also be efficacious in patients with aHUS who have received a long course of dialysis prior to eculizumab treatment [12].…”

Section: Discussionmentioning

confidence: 84%

Successful eculizumab treatment of recurrent postpartum atypical hemolytic uremic syndrome after kidney transplantation

Garlo¹,

Dressel²,

Savic

et al. 2015

CNCS

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Postpartum atypical hemolytic uremic syndrome (aHUS) is a rare disorder associated with poor maternal and fetal outcomes. We describe a case of severe postpartum aHUS with recurrence in a kidney allograft after a second pregnancy. The patient had initially presented age 28 years with aHUS that developed after her first delivery. In spite of treatment with plasma exchange, she developed end-stage renal disease (ESRD) requiring years of hemodialysis before receiving a kidney transplant from a living unrelated donor. Two years later, she became pregnant again and at 26 weeks gestation she presented to our hospital with hypertension and proteinuria. Within 48 hours of delivery she developed hemolytic anemia, thrombocytopenia, and oliguric acute kidney injury (AKI) culminating in the need for dialysis. There was no response to therapeutic plasma exchange (TPE). However, treatment with eculizumab led to prompt, successful resolution of hemolysis, thrombocytopenia, and AKI. Three months after therapy was stopped, her disease relapsed causing renal failure again requiring dialysis. At that time, an allograft biopsy revealed severe thrombotic microangiopathy (TMA). Eculizumab was resumed without plasma exchange leading to resolution of aHUS and return of kidney function. Now, her baby is nearly 2 years old. She remains on maintenance eculizumab therapy 1,200 mg every 2 weeks without dialysis. She has excellent renal function with creatinine of 1.2 mg/dL, eGFR 52 mL/min/1.73 m, and proteinuria 0.35 g/day. She will likely be on eculizumab for the remainder of her life.

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“…C5b initiates the assembly of the MAC, leading to undesirable membrane injury, while C5a recruits and activates leukocytes and upregulates vascular adhesiveness. The delicate balance between complement activation and regulation is thus disturbed on endothelial cells, resulting in a TMA (13, 14). …”

Section: Hemolytic Uremic Syndromementioning

confidence: 99%

Defective Complement Inhibitory Function Predisposes to Renal Disease

Java¹,

Atkinson

Salmon

2013

Annu. Rev. Med.

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The role of the complement system in mediating human renal disease has long been recognized in immune-complex excess syndromes such as systemic lupus erythematosus and in dense deposit disease in which no immunoglobulin (Ig) is present. Over the past 15 years, mutations in complement regulatory genes have been demonstrated to predispose to thrombotic microangiopathies including atypical hemolytic uremic syndrome, C3 and C1q glomerulopathies, and preeclampsia. Excessive complement activation on an endothelial cell, due to either an auto-antibody or a regulatory protein deficiency, sets up a procoagulant state in these diseases as well as in the antiphospholipid syndrome. Knowledge of the genes involved and the functional consequences of alterations in their structure has led to therapy that blocks complement activation.

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Clinical Grand Rounds: Atypical Hemolytic Uremic Syndrome

Cited by 24 publications

References 54 publications

An international consensus approach to the management of atypical hemolytic uremic syndrome in children

An international consensus approach to the management of atypical hemolytic uremic syndrome in children

Successful eculizumab treatment of recurrent postpartum atypical hemolytic uremic syndrome after kidney transplantation

Defective Complement Inhibitory Function Predisposes to Renal Disease

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