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Diagnosis: Atypical Hemolytic Uremic Syndrome (aHUS)

In the biopsy there is thrombotic microangiopathy. Laboratory tests led clinicians to diagnose aHUS.

Atypical hemolytic uremic syndrome is a disease characterized by acute kidney injury, thrombocytopenia, and microangiopathic hemolytic anemia. Other diseases that can present with a similar phenotype include Shiga toxin-producing E. coli-associated hemolytic uremic syndrome (STEC-HUS), thrombotic thrombocytopenic purpura, and other multisystem disorders. At least 50% of patients with aHUS have an underlying inherited and/or acquired complement abnormality, which leads to dysregulated activity of the alternative pathway at the endothelial cell surface. There are, however, noncomplement inherited abnormalities such as mutations in DGKE, which can result in an aHUS phenotype. Atypical hemolytic uremic syndrome is a “thrombotic” microangiopathy (TMA), the pathological features of which represent tissue responses to endothelial injury. In some biopsies, overt thrombosis as evidenced by intraluminal fibrin or fibrin-platelet plugging is not seen. Nonthrombotic features include endothelial swelling and denudation, mesangiolysis, double contours of the glomerular basement membrane, and subendothelial accumulation of electron-lucent, flocculent material. In arteries and arterioles, intramural fibrin, myxoid intimal thickening, and concentric myointimal proliferation (onion-skinning) may occur (Goodship TH, et al. Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference. Kidney Int. 2017;91(3):539-551. [PubMed link]).

Some clinicians now use the term “primary aHUS” when an underlying abnormality of the alternative pathway of complement is strongly suspected and other causes of secondary aHUS have been excluded. However, even in some of these patients, a complement abnormality will not be identified. In many patients with an underlying complement risk factor, a trigger is required for aHUS to manifest. Triggers include autoimmune conditions, transplants, pregnancy, infections, drugs, and metabolic conditions. It may be difficult to show unequivocally that a trigger unmasks latent complement defects. Additional work is required to define the impact of complement risk factors in these subgroups. Following the diagnosis of a TMA, clinical and laboratory evaluation is required to establish the etiology. ADAMTS13 activity is urgently required to exclude TTP prior to treatment with eculizumab in adults but is not a prerequisite in children. Investigation for STEC-HUS should be undertaken in all individuals with suspected aHUS. In all pediatric aHUS, plasma and urinary evaluation for cblC deficiency is mandatory. All individuals with suspected primary aHUS should have a complete evaluation for complement-mediated aHUS (Goodship TH, et al. Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference. Kidney Int. 2017;91(3):539-551. [PubMed link]).

See the chapter: Vascular Diseases of our Tutorial.

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References

• Zhang K, Lu Y, Harley KT, Tran MH. Atypical Hemolytic Uremic Syndrome: A Brief Review. Hematol Rep. 2017;9(2):7053. [PubMed link]
• Goodship TH, Cook HT, Fakhouri F, Fervenza FC, Frémeaux-Bacchi V, Kavanagh D, Nester CM, Noris M, Pickering MC, Rodríguez de Córdoba S, Roumenina LT, Sethi S, Smith RJ; Conference Participants. Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference. Kidney Int. 2017;91(3):539-551. [PubMed link]
• Ebrahem R, Kadhem S, Truong Q. Treatment of Atypical Hemolytic-Uremic Syndrome in the Era of Eculizumab. Cureus. 2017;9(3):e1111. [PubMed link]
• Laurence J, Haller H, Mannucci PM, Nangaku M, Praga M, Rodriguez de Cordoba S. Atypical hemolytic uremic syndrome (aHUS): essential aspects of an accurate diagnosis. Clin Adv Hematol Oncol. 2016;14 Suppl 11(11):2-15. [PubMed link]

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