Renal Involvement in Children with HUS

Abstract

The thrombotic microangiopathies consist of a heterogeneous group of diseases which have common clinical manifestations including nonimmune hemolytic anemia, thrombocytopenia, and acute kidney injury. They also share in common endothelial cell injury and microthrombus formation as the central pathologic features (Fig. 1). While they share common clinical and pathologic manifestations, they have quite different and unique etiologies, presentations, pathogenesis, and therapies [1–6]. The most common cause of hemolytic uremic syndrome (HUS) is infectious agents with Shiga toxin-producing Escherichia coli (STEC) being the predominant cause of infectious HUS (Fig. 2). Atypical HUS (aHUS) can result from genetic mutations in complement regulatory proteins including complement factors H (FH), I (FI), and B (FB), as well as other factors. Thrombotic thrombocytopenia purpura (TTP) is caused by an inherited genetic mutation or an acquired immune deficiency in a disintegrin and metalloprotease with thrombospondin type 1 repeats 13 (ADAMTS13). ADAMTS13 cleaves von Willebrand factor (VWF) facilitating its release from endothelial cells, thereby preventing the accumulation of prothrombotic ultralarge VWF oligomers. Other less common causes of HUS include drug-induced HUS, cobalamin deficiency HUS, transplant-associated HUS, and other secondary causes of HUS such as systemic lupus erythematosus and malignant hypertension. STEC HUS is usually associated with diarrhea and has been called diarrhea-positive HUS. In contrast, atypical HUS and TTP have been classified as diarrhea-negative HUS, but clearly some cases of STEC HUS have minimal gastrointestinal symptoms and some case of atypical HUS have prominent gastrointestinal symptoms [1–5]. In the majority of STEC HUS, the diarrhea is prominent, usually bloody, and associated with severe crampy abdominal pain. Diarrhea has typically begun to subside at the time HUS is developing. In contrast, diarrhea in atypical HUS is less prominent and not usually bloody. It is important to take the history, clinical findings, and laboratory values into consideration when classifying the thrombotic microangiopathies. This chapter will review the different etiologies, clinical manifestations, management, and therapy of the different causes of infectious HUS, atypical HUS, and TTP.