Pathophysiology and treatment of typical and atypical hemolytic uremic syndrome.

Hemolytic uremic syndrome is a rare disease, frequently responsible for renal insufficiency in children. Recent findings have led to renewed interest in this pathology. The discovery of new gene mutations in the atypical form of HUS and the experimental data suggesting the involvement of the complement pathway in the typical form, open new perspectives for treatment. This review summarizes the current state of knowledge on both typical and atypical hemolytic uremic syndrome pathophysiology and examines new perspectives for treatment.

Anti-Factor H autoantibodies in a fifth renal transplant recipient with atypical hemolytic and uremic syndrome.

Hemolytic uremic syndrome (HUS) associated with anti-Factor H (anti-FH) autoantibodies is a recently described pathophysiological entity. Monitoring of anti-FH IgG titer may be a sensitive marker of disease activity and guide treatment to eliminate circulating anti-FH antibodies. We report here a case of atypical HUS (aHUS) in which anti-FH autoantibodies were detected during the course of a fifth kidney transplant, 30 years after the first flare of aHUS. This exceptional case suggests that early, specific management based on immunosuppressive therapy and plasma exchanges monitored by anti-FH IgG titer may result in long-term graft survival.

The thrombotic thrombocytopenic purpura and hemolytic uremic syndromes: overview of pathogenesis (Experience of The Oklahoma TTP-HUS Registry, 1989-2007).

The Oklahoma TTP (thrombotic thrombocytopenic purpura)-HUS (hemolytic uremic syndrome) Registry, an inception cohort of 382 consecutive patients with TTP-HUS, provides a complete community perspective of these syndromes. TTP is the diagnostic term used for all adults, with or without neurologic or renal abnormalities; it is typically an acquired disorder; it may rarely result from congenital ADAMTS13 deficiency. HUS is the term used for children who have renal failure, most often caused by Escherichia coli O157:H7 infection; it may rarely result from congenital abnormalities of complement regulation. Clinical categories related to associated conditions and potential etiologies provide a structure for describing pathogenesis of the acquired syndromes. (1) Following allogeneic hematopoietic stem cell transplantation; a disorder primarily affecting kidneys described as transplantation-associated thrombotic microangiopathy. (2) Pregnancy-associated; pregnancy is a prominent risk factor for the development of TTP. (3) Drug-associated; acute, immune-mediated systemic syndromes and also dose-dependent renal toxicity. (4) Bloody diarrhea prodrome, suggesting an enteric infectious etiology. (5) Presence of an additional autoimmune disorder. (6) Idiopathic. A severe deficiency of ADAMTS13 activity contributes to the pathogenesis of many idiopathic patients and also some patients who present during pregnancy, with bloody diarrhea, or who have additional autoimmune disorders.

Síndrome hemolítico urémico / Hemolytic uremic syndrome

El síndrome hemolítico urémico incluye una triada clásica: anemia hemolítica microangiopática, trombocitopenia y disfunción renal aguda. Es preciso sospechar su diagnóstico en todo niño con historia de diarrea aguda sanguinolenta, para anticipar la evolución y las complicaciones que se asocian.

Síndrome Urémico Hemolítico Clásico / Syndrome Hemolytic Uremic

Se denomina Síndrome Uréemico Helolítico (SUH) a una entidad clínica y anatomapatológica de origen infeccioso y de características endemo epidémicas, caracterizada por anemia hemolítica microangiopática y trombocitopenia, con grados variables de afectación de la función renal

Morbilidad y Mortalidad por síndrome hemolítico urémico / Morbidity and mortality due to hemolytic uremic syndrome

Se revisaron las 201 historias clínicas de los pacientes con diagnóstico de insuficiencia renal aguda (IRA) que necesitaron algún método dialítico, en el periodo comprendido entre enero de 1980 y diciembre de 1995, en el Hospital Pediátrico Docente Centro Habana. Se seleccionaron las 10 que tenían el diagnóstico síndrome hemolítico urémico (SHU) comprobado por biopsia renal y se dividieron en SHU D+ o típico y SHU D- o atípico en relación con la presencia o ausencia de diarreas como pródromo para determinar sus características generales. El 100 por ciento de los enfermos con SHU D+ eran menores de 3 años. En este grupo la duración de los síntomas prodrómicos fue menor de 15 dias de evolución, y el hallazgo más frecuente encontrado fue la diarrea con sangre. En el 100 por ciento de los afectados con SHU D- la duración de su cuadro clínico fue de más de 15 días (anemia hemolítica trombocitopenia e insuficiencia renal aguda) y todos evolucionaron hacia la insuficiencia renal crónica. El 50 por ciento del total de los pacientes estudiados SHU (D+ y D-) presentó convulsiones y peritonitis. El SHU D- tuvo una mortalidad de 66,6 por ciento

Síndrome hemolítico urémico: una revolución conceptual en la pediatría contemporánea / Syndrome uremic hemolytic: A conceptual revolution in the contemporary pediatrics

El síndrome hemolítico urémico constituye la primera causa de insuficiencia renal aguda (IRA) de la infancia. Para su estudio se clasifica en típico o D+ si se asocia a un cuadro diarréico agudo y atípico o D- si no se recoge este antecedente. El cuadro clínico se caracteriza por la tríada compuesta por anemia hemolítica microangiopática, trombocitopenia e insuficiencia renal aguda, a la que se le puede asociar fiebre y convulsiones. Actualmente debido a su patogenia, para la cual se invocan receptores fisiológicos de membrana (Globotriaosylcermide Gb3), el cuadro clínico puede ser variable y presentarse como síndrome de falla multiorgánica. El tratamiento es sintomático y los métodos dialíticos son opciones terapéuticas para eliminar la congestión vascular periférica y el factor inhibidor del activador del plasminógeno que sirve de pronóstico a corto y largo plazo de la función renal

Adult hemolytic-uremic syndrome. A review of 37 cases.

BACKGROUND: Adult hemolytic-uremic syndrome is a serious, poorly understood disease with a high and variable mortality. We studied several demographic, clinical, and treatment variables, related them to outcome, and developed a new classification. METHODS: We analyzed data from 37 patients admitted from 1981 to 1991 who fulfilled four criteria (age > 16 years, microangiopathic hemolytic anemia, creatinine level > 150 mumol/L [> 1.7 mg/dL], and no artificial heart valve). Three outcome variables were studied (survival vs death, recurrence vs no recurrence, and chronic renal failure vs no chronic renal failure). RESULTS: Eleven (30%) of the patients died, 10 (27%) needed dialysis, five (14%) developed chronic renal failure, and nine (24%) had recurrent episodes. Patients who presented with colitis did not die or have recurrences, but they developed chronic renal failure as often as other patients. Patients with hemolytic-uremic syndrome secondary to other diseases had the worst survival and the most recurrences. Those without any triggering factor (primary cases) were in between. In multivariate analysis, hemolytic-uremic syndrome secondary to colitis, a higher white blood cell count at admission, and a high maximum mean arterial pressure were associated with good survival prognosis. CONCLUSIONS: The persistence of the trigger of adult hemolytic-uremic syndrome sets the stage for outcome. If the trigger is transient (such as Escherichia coli colitis), the disease will not recur and is rarely lethal. If no trigger is apparent (primary hemolytic-uremic syndrome) or the trigger persists (systemic lupus erythematosus and cancer), the syndrome has a high mortality and often recurs. We suggest a new classification: (1) extrinsic hemolytic-uremic syndrome: (a) toxic, (b) infectious; (2) intrinsic hemolytic-uremic syndrome: (a) primary, (b) secondary. The use of this classification, combined with simple data obtained at presentation and a further division of the cause as transient or persistent and irreversible, may improve the selection of therapy.