Hemolytic-uremic syndrome (HUS) was first described by Gasser in a German publication in 1955. Hemolytic-uremic syndrome consists of the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Since 1955, thousands of cases have been reported, and hemolytic-uremic syndrome is recognized as the most common cause of acute renal failure in the pediatric population.
The clinical course of hemolytic-uremic syndrome can vary from subclinical to life threatening. Studies have revealed distinct subgroups of hemolytic-uremic syndrome and have identified several etiologies for the disease. Hemolytic-uremic syndrome is classified as diarrhea-associated (D+ hemolytic-uremic syndrome) and non–diarrhea-associated (D- or atypical hemolytic-uremic syndrome). Within D- hemolytic-uremic syndrome is another subtype, pneumococcal-associated hemolytic-uremic syndrome (P-hemolytic-uremic syndrome). The distinction is important because the clinical courses, treatments, and prognoses differ for each category. The first reported cases were D- hemolytic-uremic syndrome; however, D+ hemolytic-uremic syndrome is now much more common.
Hemolytic-uremic syndrome shares many features with thrombotic thrombocytopenic purpura (TTP). For more information, see the Medscape Reference article Thrombotic Thrombocytopenic Purpura. Both diseases include multiorgan dysfunction due to thrombotic microangiopathy, with active hemolysis and thrombocytopenia. The traditional classification describes patients with predominantly renal disease as having hemolytic-uremic syndrome, and patients with predominantly CNS disease as having TTP. However, hemolytic-uremic syndrome can include severe neurologic impairment, and TTP can involve severe renal failure. Involvement of other organ systems also overlaps.
Whether these are, in fact, separate diseases remains controversial; some authors describe "hemolytic-uremic syndrome–TTP" as a single disease entity with a diverse spectrum of presentations. In many cases, both nephrologists and hematologists collaborate on the care of patients with these complex illnesses.
Nomenclature for various types of hemolytic-uremic syndrome varies throughout the literature. For consistency, this article uses the following set of terms throughout this review:
D+ hemolytic-uremic syndrome is used to describe diarrhea-positive, classic or typical hemolytic-uremic syndrome, mediated by Shiga toxin (Stx).
D- hemolytic-uremic syndrome is used to describe diarrhea-negative, non–diarrhea-associated or atypical hemolytic-uremic syndrome, mediated by abnormalities of the complement system or other heritable factors.
P-hemolytic-uremic syndrome is used to describe pneumococcal-associated hemolytic-uremic syndrome, mediated by neuraminidase in the presence of infection with Streptococcus pneumoniae.