Atypical hemolytic uremic syndrome in a patient with protein-losing enteropathy

Abstract

Atypical hemolytic uremic syndrome (aHUS) is an ultra-rare disease induced by many triggers, all of which produce a common end phenotype of microangiopathic hemolysis and thrombotic microangiopathy. We herein describe a 63-year-old woman with ongoing protein-losing enteropathy and frequent transudates caused by hypoalbuminemia. The patient was treated with eculizumab with a full hematologic and partial renal response. Protein-losing enteropathy is an inflammatory condition that has been linked with increased complement activation, which can trigger aHUS in patients with loss of CD55 expression. The patient in the present case had an increased estimated glomerular filtration rate but stage IV to V chronic kidney disease. One year later, she remains off dialysis with a stable estimated glomerular filtration rate. We herein report an unusual trigger of complement activation that in turn triggered aHUS in this patient.

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

“…Similar CFH gene mutations have been shown in the literature to accelerate the predisposition to aHUS and the development of lupus nephritis in accurate mouse models (MRL-lpr mice) [8]. Diagnosis of aHUS is done after exclusion of other microangiopathic hemolytic anemias and with possible findings of a pathologic variant mutation or deletion [3]. Traditional therapies include plasma exchange, glucocorticoids, and immune therapies, but recent clinical trials have shown complement inhibition with eculizumab to induce remission of acute episodes of aHUS and prevention of TMA events refractory to plasma therapy.…”

“…The activation of the alternative pathway of the complement system in hemolytic uremic syndrome has been known since 1975 [1][2][3]. The complement system plays an important part in the adaptive and innate immune systems and consists of more than 40 plasma and membrane-associated proteins [1].…”

“…Thrombotic microangiopathies (TMAs) are a diverse group of diseases presenting with features of microangiopathic hemolytic anemia, thrombocytopenia, and end-organ dysfunction [1, 2]. Complement-mediated TMA, referred to as atypical hemolytic uremic syndrome (aHUS), is an extremely rare (or possibly rarely recognized) disease caused by deficiencies of complement-regulatory proteins that control the alternative complement system [3, 4]. 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).…”

Finding of pathological thrombomodulin gene variant in a patient with idiopathic nodular glomerulosclerosis and chronic thrombotic microangiopathy-like changes

“…The thrombomodulin mutation identified is a recognized pathogenic variant of alternative complement pathway dysfunction. 11 , 12 The lack of peripheral hemolysis suggests a renal limited TMA presentation, despite the finding of low platelets systemically. It is important to note that the lack of systemic hemolysis does not preclude the existence of TMA, and the finding seen in this case is reminiscent of Timmermans et al 13 about arteriolar injury and complement dysfunction in patients with chronic hypertension.…”

Refractory scleroderma renal crisis precipitated after high-dose oral corticosteroids and concurrent intravitreal injection of bevacizumab

“…1 There are many complex pathways involved; however, it has become clear that endothelial injury can occur more easily in certain genetically susceptible individuals. 2 It has also been observed that if endothelial damage and complement activation are sufficiently severe, TMA can occur despite the appearance of an apparently benign genetic environment. 3 Scleroderma renal crisis (SRC) usually presents with a TMA that occurs within the context of malignant hypertension (MHT) and progressive renal dysfunction.…”