Atypical hemolytic uremic syndrome and complement blockade

Hanna, Ramy M; Barsoum, Marina; Vandross, Andrae; Kurtz, Ira; Burwick, Richard M.

doi:10.1097/mnh.0000000000000499

Cited by 14 publications

(7 citation statements)

References 78 publications

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“…Our case emphasizes the need for a high degree of clinical understanding and awareness surrounding complement-mediated TMA [6], as well as an association with pregnancy and SLE as primary drivers of the disease [7, 11]. Although plasma-based therapeutics can be initiated, clinicians should have a low threshold for moving to terminal-complement inhibition with eculizumab, particularly if ADAMTS-13 activity is detectable.…”

Section: Discussionmentioning

confidence: 99%

“…Patients with alternative complement pathway dysregulation in the form of complement factor H (CFH) mutations have the worst long-term prognosis, with 73% progressing to end-stage renal disease within 5 years after diagnosis (in those without anti-factor H autoantibodies). Since the clinical and laboratory presentation of lupus nephritis with TMA is very similar to aHUS [5, 6], the use of complement inhibition is appropriate in certain settings [7-9].…”

Section: Introductionmentioning

confidence: 99%

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Complement-Mediated Thrombotic Microangiopathy Associated with Lupus Nephritis Treated with Eculizumab: A Case Report

Torres

Chang

Desai

et al. 2021

Case Rep Nephrol Dial

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Thrombotic microangiopathies (TMAs) involve multiple organ systems due to the presence of microangiopathic hemolysis. One such condition, atypical hemolytic uremic syndrome (aHUS), is a complement-mediated process that is part of a spectrum of disorders that have underlying complement dysfunction of the alternative pathway due to overactivity or decreased self-nonself discrimination by innate immunity. Complement-amplifying conditions such as pregnancy may unmask a diagnosis of aHUS. We present an important case of a pregnant 23-year-old Hispanic female who presented in mid-gestation (21 weeks) with an initial diagnosis of systemic lupus erythematosus (SLE) complicated by aHUS. She met clinical criteria for aHUS on presentation and was found to have a pathogenic CFHR1–3 homozygous deletion. She has been treated with intravenous and oral steroids, cyclophosphamide, subsequently also with plasma exchange, and finally with eculizumab with partial improvement in renal function. This case adds to the emerging literature showing that SLE and aHUS (or complement-mediated TMA) can be successfully treated with C5 blockade.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Complement-Mediated Thrombotic Microangiopathy Associated with Lupus Nephritis Treated with Eculizumab: A Case Report

Torres

Chang

Desai

et al. 2021

Case Rep Nephrol Dial

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“…In our experience, oral corticosteroids for treatment of cFSGS lesions induced while patients were getting intravitreal VEGF blockade were not uniformly successful. Given the emerging evidence of efficacy of complement blockade in some secondary forms of TMA/atypical hemolytic uremic syndrome, use of complement factor 5 blockade may be a therapeutic option (50).…”

Section: Discussionmentioning

confidence: 99%

Thrombotic Microangiopathy and Acute Kidney Injury Induced After Intravitreal Injection of Vascular Endothelial Growth Factor Inhibitors VEGF Blockade-Related TMA After Intravitreal Use

et al. 2020

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Vascular endothelial growth factor (VEGF) inhibition can cause worsening hypertension, proteinuria, chronic kidney injury, and glomerular disease. Thrombotic microangiopathy (TMA) and other nephrotic disorders have been reported with systemic VEGF blockade. These same agents are given intravitreally for age-related macular degeneration (AMD) and diabetic retinopathy (DR), albeit at lower doses than those given for systemic indications. Systemic absorption of anti-VEGF agents when given intravitreally has been shown consistently along with evidence of significant intravascular VEGF suppression. While worsening hypertension has only been seen in some large-scale studies, case reports show worsening proteinuria and diverse glomerular diseases. These include TMA-associated lesions like focal and segmental glomerulosclerosis with collapsing features (cFSGS). In this paper, we report three cases of TMA likely associated with the use of intravitreal anti-VEGF therapy. These patients developed the signature lesion of VEGF blockade in a 6 to 11 month time frame after starting intravitreal VEGF inhibitors. The literature is reviewed showing similar cases. Intravitreal VEGF blockade may cause these adverse events in a hitherto unidentified subgroup of patients. Well-controlled prospective observational trials are needed to determine the event rate and identify which subgroups of patients are at increased risk. A registry for patients who develop worsening hypertension, proteinuria exacerbation, and glomerular diseases from intravitreal VEGF blockade is proposed.

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“…Certain conditions may mimic a TMA-like state. Severe cobalamin deficiency, widely disseminated cancer, acute fatty liver of pregnancy, and decompensated cirrhosis are examples [34]. In a review of patients with severe cobalamin deficiency masquerading as TMA, 100% had low hemoglobin, 76% schistocytosis and median (range) LDH (U/L) of 3981 (2004-5467); features were so similar to TTP that plasma exchange or infusion was instituted in 14 of 41 (34%) cases.…”

Section: 33mentioning

confidence: 99%

“…Other causes of TMA include hypertensive emergency, scleroderma renal crisis, disseminated intravascular coagulation (DIC), shiga-toxin mediated TMA (i.e., classical HUS), and thrombotic thrombocytopenic purpura (TTP) [19 ▪▪ ,33 ▪ ,34]. In TTP, deficiency of a d isintegrin a nd m etalloprotease with a t hrombospondin type 1 motif, member 13 (ADAMTS-13) causes accumulation of ultra large molecular weight multimers of von Willebrand Factor (VWF), systemic microvascular thrombosis, consumptive thrombocytopenia, MAHA, and end organ involvement.…”

Section: Thrombotic Microangiopathies: Multiple Causes and Disease Mi...mentioning

confidence: 99%

Thrombotic microangiopathy – the importance of a multidisciplinary approach

Tran,

Patel,

Desai

et al. 2023

Current Opinion in Nephrology &Amp; Hypertension

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Purpose of review The purpose of this review is to highlight the importance of a multidisciplinary thrombotic microangiopathies (TMA) Team. This goal will be accomplished through review of the complement system, discuss various causes of thrombotic microangiopathies (TMA), and aspects of their diagnosis and management. In so doing, readers will gain an appreciation for the complexity of this family of disorders and realize the benefit of a dedicated multidisciplinary TMA Team. Recent findings TMA causes derive from multiple specialty areas, are difficult to timely recognize, pose complex challenges, and require multidisciplinary management. Hematopoietic stem cell transplant-associated TMA (TA-TMA) and TA-TMA related multiorgan dysfunction syndrome (TA-TMA MODS) are areas of burgeoning research; use of complement testing and eculizumab precision-dosing has been found to better suppress complement activity in TA-TMA than standard eculizumab dosing. Newer tests are available to risk-stratify obstetric patients at risk for severe pre-eclampsia, whose features resemble those of TA-TMA MODS. Numerous disorders may produce TMA-like findings, and a systematic approach aids in their identification. TMA Teams elevate institutional awareness of increasingly recognized TMAs, will help expedite diagnostic and therapeutic interventions, and create pathways to future TMA-related research and facilitate access to clinical trials. Summary Establishment of a TMA-Team is valuable in developing the necessary institutional expertise needed to promptly recognize and appropriately manage patients with TMA.

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Atypical hemolytic uremic syndrome and complement blockade

Cited by 14 publications

References 78 publications

Complement-Mediated Thrombotic Microangiopathy Associated with Lupus Nephritis Treated with Eculizumab: A Case Report

Complement-Mediated Thrombotic Microangiopathy Associated with Lupus Nephritis Treated with Eculizumab: A Case Report

Thrombotic Microangiopathy and Acute Kidney Injury Induced After Intravitreal Injection of Vascular Endothelial Growth Factor Inhibitors VEGF Blockade-Related TMA After Intravitreal Use

Thrombotic microangiopathy – the importance of a multidisciplinary approach

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