Recovery of thalamic microstructural damage after Shiga toxin 2-associated hemolytic-uremic syndrome.

INTRODUCTION: The underlying pathophysiology of neurological complications in patients with hemolytic-uremic syndrome (HUS) remains unclear. It was recently attributed to a direct cytotoxic effect of Shiga toxin 2 (Stx2) in the thalamus. Conventional MRI of patients with Stx2-caused HUS revealed - despite severe neurological symptoms - only mild alterations if any, mostly in the thalamus. Against this background, we questioned: Does diffusion tensor imaging (DTI) capture the thalamic damage better than conventional MRI? Are neurological symptoms and disease course better reflected by thalamic alterations as detected by DTI? Are other brain regions also affected? METHODS: Three women with serious neurological deficits due to Stx2-associated HUS were admitted to MRI/DTI at disease onset. Two of them were longitudinally examined. Fractional anisotropy (FA) and mean diffusivity were computed to assess Stx2-caused microstructural damage. RESULTS: Compared to 90 healthy women, all three patients had significantly reduced thalamic FA. Thalamic mean diffusivity was only reduced in two patients. DTI of the longitudinally examined women demonstrated slow normalization of thalamic FA, which was paralleled by clinical improvement. CONCLUSION: Whereas conventional MRI only shows slight alterations based on subjective evaluation, DTI permits quantitative, objective, and longitudinal assessment of cytotoxic cerebral damage in individual patients.

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.

Pathogenesis and treatment of Shiga toxin-producing Escherichia coli infections.

PURPOSE OF REVIEW: Shiga toxin-producing Escherichia coli cause hemorrhagic colitis and hemolytic uremic syndrome. We will summarize the literature on incidence and outcomes of these infections, and then review the pathogenesis to explain the current recommendations against antibiotic use and to suggest alternative therapies. RECENT FINDINGS: Shiga toxin-producing E. coli continue to be prevalent in the industrialized world because of dissemination in food products contaminated by ruminant feces. Declines in ground beef-related outbreaks have been matched by increased cases related to green vegetables. Fifteen percent of patients infected with E. coli O157:H7 progress to hemolytic uremic syndrome, but this figure may reach 50% if antibiotics are used. Mechanisms for bacteriophage induction causing Shiga toxin production, and for Shiga toxin dissemination to endothelium in gut, kidney and brain, may explain the negative effects of antibiotics and lead to rational therapies. Shiga toxin binders were not effective in clinical trials, but more avid binding agents may be. Current treatment recommendations are to maintain hydration to prevent thrombotic complications. Human vaccines are unlikely to be utilized. Cattle vaccines may prove the most significant approach to this disease. SUMMARY: Improved understanding of Shiga toxin-producing Escherichia coli pathophysiology and progression to hemolytic uremic syndrome provides the basis for prevention, prophylactic and treatment strategies.

Síndrome hemolítico urémico en Santiago de Chile: evolución de la función renal y factores pronósticos / Hemolytic uremic syndrome (HUS), prognostic factors and follow up of renal function, in Santiago, Chile

Introducción: El Síndrome Hemolítico Urémico (SHU) se caracteriza por falla renal aguda, anemia hemolítica microangiopática y trombocitopenia; es la causa más frecuente de insuficiencia renal aguda en la infancia. Objetivo: a) Describir las características actuales del cuadro inicial de SHU en nuestro medio y comparar con lo descrito anteriormente; b) Describir la evolución a 1 año plazo y evaluar posibles factores pronósticos de función renal. Sujetos y Métodos: Se estudiaron variables demográficas, presentación clínica, exámenes bioquímicos y hematológicos, en 374 pacientes con SHU diagnosticados entre Enero 1990 a Diciempe 2002 en 9 hospitales de la Región Metropolitana; se evaluó además función renal al año de seguimiento en una muestra de 213 pacientes y se identificaron factores pronósticos de insuficiencia renal crónica y mortalidad utilizando el análisis de regresión logística. Resultados: Se analizaron 374 pacientes, 50,5 por ciento mujeres, 65,5 por ciento de la Región Metropolitana, edad promedio 1,5 ± 1,4 años (0,2 a 8); 91 por ciento presentó diarrea, 31 por ciento ocurrió en verano, al ingreso 57 por ciento presentó anuria, 43,3 por ciento hipertensión arterial y convulsiones 23 por ciento. Al alta 28 por ciento persistía hipertenso. Las terapias de sustitución renal utilizadas fueron: diálisis peritoneal (50 por ciento), hemodiafiltración (6 por ciento) y hemodiálisis (3 por ciento); recibió plasmaféresis 1 por ciento. Se aisló agente etiológico en 17 por ciento, siendo en 69 por ciento E. coli enterohemorrágica. La mortalidad fue de 2,7 por ciento, siendo la causa principal la falla orgánica múltiple. En el seguimiento al año: 80 por ciento mantuvo función renal normal, 14 por ciento presento deterioro de la función renal, 6 por ciento proteinuria y 4 por ciento hipertensión. Se encontró significativo como factor pronóstico de daño renal: hipertensión arterial (p < 0,0001), necesidad de peritoneodiálisis y hemodiálisis (p: 0,001, p: 0,0015 respectivamente), anuria (p: 0,005) y convulsiones (p: 0,01). Se correlacionó con mortalidad en la etapa aguda: convulsiones, requerimiento de hemodiafiltración y plasmaféresis, (p < 0,0001, p: 0,0001 y p < 0,0001 respectivamente).

Hemolytic uremic syndrome: urate nephropathy superimposed on an acute glomerulopathy? An hypothesis.

The oligo-anuria of the hemolytic uremic syndrome is attributed to the presence of a renal lesion which is predominantly glomerulopathic but which may have a vasculopathic component of varying severity. Fourteen children, four of whom had anuric, four oliguric and six non oliguric acute renal failure were treated with intravenous fluids and high dose intravenous furosemide therapy. Polyuria was induced in all, obviating the need for dialysis. We hypothesize that oligo-anuria in this syndrome may be due to the previously recognized hyperuricemia causing a urate nephropathy superimposed on the glomerulopathy thus explaining its possible amenability to fluid and diuretic therapy.

[Microangiopathic hemolytic anemias. Clinical pattern, therapy and clinical course in 14 patients with thrombotic thrombocytopenic purpura and hemolytic uremic syndrome]. / Die mikroangiopathischen hämolytischen Anämien. Klinik, Therapie und Verlauf bei 14 Patienten mit thrombotisch-thrombozytopenischer Purpura und hämolytisch-urämischem Syndrom.

Thrombotic thrombocytopenic purpura (TTP) and the hemolytic uremic syndrome (HUS) have in common a microangiopathic hemolytic anemia involving disseminated platelet aggregation and endothelial damage of the microvasculature mainly of the brain (TTP) and kidney (HUS). The underlying pathomechanism still remains unclear. The disease takes an acute, dramatic and frequently fatal course. Unfortunately a broadly approved therapeutic regimen is still lacking since the rarity of TTP and HUS makes study of a large group of patients impossible. We have observed and treated 14 patients with TTP and HUS during a period of 9 years. Most of the cases have been triggered by infectious diseases and pregnancy. Diagnostic cornerstones were hemolytic anemia, schistocytes on peripheral blood smears and consumption thrombocytopenia. Renal and cerebral symptoms were observed regularly, whereas lesions of the pancreas, liver and heart were much less frequent. The treatment included plasma transfusion (47%), plasma exchange (42%), high dose corticosteroids (74%), antiplatelet agents (53%), vitamin E (32%) and vincristin (11%). The outcome of 19 episodes of TTP or HUS was as follows: in 78% complete recovery, in 11% persistence of impaired renal function, and in 11% death. From analysis of our cases it is concluded that plasma transfusions and high dose corticosteroids improve the prognosis of TTP and HUS significantly.