Sindrome

hemolítico-urêmica

Antonio Souto

acasouto@bol.com.brMédico coordenador

Unidade de Medicina Intensiva PediátricaUnidade de Medicina Intensiva Neonatal

Hospital Padre Albino

Professor de Pediatria nível II Faculdades Integradas Padre Albino

Catanduva / SP2011

Hemolytic uremic syndrome is

the most common cause of acute

renal failure in children,

and the incidence of this syndrome in

children is increasing worldwide.

Epidemiology

•Primarily occurs in children one to 10 years of age

•Annual incidence: 1-3/100,000

•Survival rate of nearly 90 percent

•Rural populations are more at risk

•Incidence is higher in warmer months

•Three to 15 percent of persons who have STEC with

diarrhea

E. coli O157:H7 strains could survive for as long as

one year

Am Fam Physician 2006;74:991-6, 998.

Epidemiology

Risk factors:

•Age

•Bloody diarrhea

•Fever

•Elevated white blood cell count

•Elevated C-reactive protein levels

•The use of antibiotics or antimotility/antidiarrheal

and antimicrobial agents

Am Fam Physician 2006;74:991-6, 998.

Etiology

Two types (diarrheal prodrome)

•Diarrhea-positive

Shiga toxin–producing Escherichia

coliE. coli O157:H7 other strains also have been

implicated

Diarrhea-negative in adults can have a genetic cause

and generally has a poor prognosis

Etiology

E. coli O157:H7 is believed to cause more than 80

percent of the STEC infections that lead to

hemolytic uremic syndrome.

Form of transmission to children

•ingestion of undercooked beef containing E. coli

•by contact with persons who inadequately wash

their hands, resulting in fecal and oral

contamination and transmission

Etiology

There is increasing awareness that

other organisms, drugs, and conditions

can also initiate the triad of

microangiopathic hemolytic anemia,

thrombocytopenia, and acute

nephropathy that defines HUS.

Current Opinion in Pediatrics 2005, 17:200–204

. Distribution of hemolytic uremic syndrome cases associated with Shiga toxin–producing

Escherichia coli O157, 026, O111, and O145, by year

Shiga Toxin

Toxin is almost identical to Stx from Shigella

dysenteriae

Stx cause different degrees and types of tissue

damage

Higher pathogenicity of strains that produce only

Stx-2, most commonly associated with HUS

•Oral ingestion

• Stx-E. coli reaches the gut and closely adheres to

the epithelial cells

• Stx then translocate into the circulation

•Transport of Stx from the intestine to the kidney,

consistently, Stx bound to circulating PMN

•In vitro, PMN loaded with Stx transfer the ligand to

glomerular endothelial cells

•The findings indicate that Stx favor leukocyte-

dependent inflammation.

•Activates endothelial cells that leads to

microvascular thrombosis.

•In vivo evidence of coagulation disturbances has

been found in children who developed HUS upon E.

coli O157:H7 infection.

•Recent work indicating that fibrinolysis is

substantially inhibited.

Clinical Characteristics

The classic triad:

•Microangiopathic hemolytic anemia

•Thrombocytopenia

•Acute renal failure

Typical hemolytic uremic syndrome usually develops

after a prodrome of diarrhea.

Clinical Characteristics

•Clinical features are vague and may mimic common

gastroenteritis

•Bloody diarrhea three days to more than two

weeks before HUS

•Additional symptoms:

•Nonbloody diarrhea, abdominal cramping and

nausea or vomiting.

•Fever low grade or absent.

•Ten percent of cases rectal prolapse with colitis

HUS cannot be diagnosed

without evidence of hemolytic

anemia.

Hematologic findings:

•Destruction and fragmentation of erythrocytes

•Microangiopathic hemolytic anemia

•92% develop thrombocytopenia

•Clotting times are normal

•Petechiae and purpura are uncommon

Schistocytes are fragmented red blood cells,

and indicate mechanical damage causing

hemolysis.

AAAAcute renal failure

When microthrombi are deposited in kidney

parenchyma

•Hypertension

•Oliguria and anuria

•Edema

Microvascular

•Vessel wall thickening

•Endothelial swelling

•Accumulation of proteins and cell debris in the

subendothelial layer

Microvascular

•`The lesion is mainly confined to the glomerular tuft

and is noted in an early phase of the disease.

•Biopsies showed that most glomeruli are normal,

whereas 15 to 20% eventually became sclerotic.

Am Fam Physician 2006;74:991-6, 998.

Am Fam Physician 2006;74:991-6, 998.

Management

Is There Any Effective Treatment for

Stx-HUS?

There is no treatment of proven

value, and care during the acute

phase of the illness is still merely

supportive

Management

HUS is a selflimiting disease

•Close monitoring and treatment of symptoms are

essential

•Wide spectrum of presentations

•Supportive therapy

•Close monitoring of fluid and electrolyte status

The amount of parenteral hydration before the

development of HUS, is crucial in preventing anuria

and, ultimately, dialysis.

Management

Detecting early renal failure

•Should be handled aggressively

•Renal replacement therapy (peritoneal dialysis)

•Hypertension is treated traditionally

Antibiotics and antimotility agents are not

recommended as treatments for hemolytic uremic

syndrome during the diarrheal stage of the disease.

Management

Studies of antibiotic usage in children with E. coli

O157:H7 infections show an increased risk of

complications from HUS

Management

On the basis of available data, we

suggest that in patients with Stx-E.

coli gastrointestinal infection,

antibiotics should be avoided unless

in cases with sepsis.

Management

Serial monitoring of the hematocrit and platelet

count is important

•Platelet transfusion can worsen the thrombotic

process

•Transfusion of red blood cells may be needed

•Transfusion can deteriorate the patient’s

condition

Management

Renin-angiotensin system blockade may be

particularly beneficial

•Early restriction of proteins and use of angiotensin-

converting enzyme inhibitors may have a beneficial

effect

•Treatment with angiotensin-converting enzyme

inhibitors normalized BP, reduced proteinuria, and

improved GFR.

Am Fam Physician 2006;74:991-6, 998.

Complications

Chronic renal failure

12% develop end-stage renal disease

Additional complications:

Hypertension, proteinuria, renal impairment,

pancreatitis, cerebral involvement, cardiomyopathy,

and gastrointestinal involvement

Complications

10% of patients

Central nervous system

problems

coma, hemiparesis, or stroke

3,476 patients with diarrhea-positive hemolytic

uremic syndrome, 313 (9%) died, 104 (3%)

developed end-stage renal disease, and 869 (25%)

exhibited renal sequelae

Neurologic involvement correlates highly with a

fatal outcome