Complement in Secondary Thrombotic Microangiopathy

Palma, Lílian Monteiro Pereira; Sridharan, Meera; Sethi, Sanjeev

doi:10.1016/j.ekir.2020.10.009

Cited by 73 publications

(85 citation statements)

References 120 publications

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“…Drug induced TMA (DITMA) is suspected when there is a sudden onset acute kidney injury, usually within hours or a few days after drug exposure, and resolution can be observed when the drug is stopped or reduced (57,89,113). The association between CNIs and de novo PT-TMA has been well documented in the literature, with the risk higher with cyclosporine than with tacrolimus (41).…”

Section: Drug-induced Thrombotic Microangiopathymentioning

confidence: 99%

Thrombotic Microangiopathy After Kidney Transplantation: An Underdiagnosed and Potentially Reversible Entity

2021

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Thrombotic microangiopathy is a rare but serious complication that affects kidney transplant recipients. It appears in 0.8–14% of transplanted patients and negatively affects graft and patient survival. It can appear in a systemic form, with hemolytic microangiopathic anemia, thrombocytopenia, and renal failure, or in a localized form, with progressive renal failure, proteinuria, or arterial hypertension. Post-transplant thrombotic microangiopathy is classified as recurrent atypical hemolytic uremic syndrome or de novo thrombotic microangiopathy. De novo thrombotic microangiopathy accounts for the majority of cases. Distinguishing between the 2 conditions can be difficult, given there is an overlap between them. Complement overactivation is the cornerstone of all post-transplant thrombotic microangiopathies, and has been demonstrated in the context of organ procurement, ischemia-reperfusion phenomena, immunosuppressive drugs, antibody-mediated rejection, viral infections, and post-transplant relapse of antiphospholipid antibody syndrome. Although treatment of the causative agents is usually the first line of treatment, this approach might not be sufficient. Plasma exchange typically resolves hematologic abnormalities but does not improve renal function. Complement blockade with eculizumab has been shown to be an effective therapy in post-transplant thrombotic microangiopathy, but it is necessary to define which patients can benefit from this therapy and when and how eculizumab should be used.

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Section: Drug-induced Thrombotic Microangiopathymentioning

confidence: 99%

Thrombotic Microangiopathy After Kidney Transplantation: An Underdiagnosed and Potentially Reversible Entity

2021

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Section: Introductionmentioning

confidence: 99%

“…Thrombotic microangiopathy (TMA) is a rare group of diseases characterized by microangiopathic hemolytic anemia, thrombocytopenia, and target organ damage [ 1 , 2 , 3 , 4 , 5 ]. TMA can be divided into primary (genetic and acquired) and secondary TMA [ 1 , 2 ]. Primary genetic causes encompass: deficiency of ADAMTS13 (known as thrombotic thrombocytopenic purpura (TTP)); complement-mediated hemolytic uremic syndrome (HUS), also known as atypical hemolytic uremic syndrome (aHUS) [ 1 , 2 , 5 ]; cobalamin C hemolytic uremic syndrome, due to a rare autosomal recessive disorder of cobalamin metabolism [ 2 , 5 ]; and mutations in DGKE (diacylglycerol epsilon), and in the INF2 (inverted formin 2) gene [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

“…TMA can be divided into primary (genetic and acquired) and secondary TMA [ 1 , 2 ]. Primary genetic causes encompass: deficiency of ADAMTS13 (known as thrombotic thrombocytopenic purpura (TTP)); complement-mediated hemolytic uremic syndrome (HUS), also known as atypical hemolytic uremic syndrome (aHUS) [ 1 , 2 , 5 ]; cobalamin C hemolytic uremic syndrome, due to a rare autosomal recessive disorder of cobalamin metabolism [ 2 , 5 ]; and mutations in DGKE (diacylglycerol epsilon), and in the INF2 (inverted formin 2) gene [ 2 ]. Primary acquired TMA causes include: TTP secondary to autoantibodies to ADAMTS13 and complement-mediated HUS secondary to autoantibodies, most commonly against factor H (FH).…”

Section: Introductionmentioning

confidence: 99%

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Thrombotic microangiopathy triggered by podocytopathy

Veríssimo¹,

Mateus²,

Laranjinha³

et al. 2021

CNCS

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Thrombotic microangiopathy (TMA) is a rare group of diseases characterized by microangiopathic hemolytic anemia, thrombocytopenia, and target organ damage. It can be divided into primary and secondary TMA. Herein we report a case of TMA associated to a primary glomerular disease. We report the case of a 31-year-old Black male from Cape Verde admitted in March 2018 with nephrotic syndrome and upper gastrointestinal bleeding, the latter due to severe erythematous gastritis. He was discharged after clinical stabilization. The patient came to Portugal 8 months later. On admission, he presented with rapid deterioration of kidney function and hyperkalemia. The etiologic study revealed microangiopathic hemolytic anemia, nephrotic syndrome and microscopic hematuria. Immunologic study and viral serology were negative. ADAMTS13 activity and inhibitor testing were within normal range, genetic complement evaluation showed CFH-H3 in homozygosity, functional complement studies revealed decreased function of alternative pathway. Kidney biopsy was consistent with the diagnosis of TMA, and electron microscopy was compatible with minimal change disease. Patient underwent plasmapheresis with resolution of hemolysis, fluid overload and recovery of renal function. Two months later, he presented with nephrotic syndrome and started prednisolone with remission. Six months later, the nephrotic syndrome relapsed, and it became steroid-, MMF-, and rituximab-resistant. Tacrolimus was initiated, achieving partial remission. Atypical hemolytic uremic syndrome is an uncommon disease and is rarely reported as secondary to glomerular diseases. This case showcases the challenges regarding treatment options in a resistant glomerulopathy and the implications of therapeutic choices and kidney outcomes with the coexisting TMA.

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“…One of the main challenges is to differentiate aHUS unmasked by a trigger from secondary causes of Thrombotic Microangiopathy (TMA) - those in which the underlying cause has a direct role in endothelial damage. In a recent review 8 , severity and extent of genetic complement abnormalities in secondary TMA was shown to be variable. Malignant hypertension and pregnancy-associated TMA are more likely to be associated with genetic complement abnormalities, and appear similar to those in aHUS, whereas autoimmune diseases and drug-associated TMA are less likely to have genetic complement abnormalities.…”

mentioning

confidence: 99%

Complement in Secondary Thrombotic Microangiopathy

Cited by 73 publications

References 120 publications

Thrombotic Microangiopathy After Kidney Transplantation: An Underdiagnosed and Potentially Reversible Entity

Thrombotic Microangiopathy After Kidney Transplantation: An Underdiagnosed and Potentially Reversible Entity

Thrombotic microangiopathy triggered by podocytopathy

Rare and Complex: lessons from a cohort of patients with Atypical Hemolytic Uremic Syndrome

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