HEMOLYTIC UREMIC SYNDROME

Hemolytic uremic syndrome (HUS) is a leading cause of acute renal failure in young children, characterized by a triad of: (a) microangiopathic hemolytic anemia, (b) thrombocytopenia, and (c) acute renal insufficiency.

• Typical HUS is associated with Shiga-toxin or shiga- like toxin producing enteropathogens (also termed as Shiga-toxin associated HUS or STEC-HUS), usually seen in infants and toddlers following an episode of diarrhea/ dysentery; and

• Atypical HUS which is less common, seen in older children without antecedent diarrhea/dysentery and associated with genetic abnormalities of alternate complement or thrombotic pathway. However, some attacks may be precipitated by infections, e.g. pneumococci or drugs, e.g. cyclosporine. Secondary HUS following SLE, cancers and marrow transplant is also known.

Etiopathogenesis: Typical HUS in Indian children is usually associated with an attack of bacillary dysentery due to Shiga-toxin producing enteropathogens, e.g. Shigella dysenteriae 1, while a Shiga-toxin like verotoxin producing E. coli (e.g. E. coli O157:H7) is more important cause in Europe and North America.

Cytotoxic injury to endothelium of renal microvasculature due to shiga-like toxins is the primary event in HUS, which provokes activation of platelets and coagulation factors, leading to localized coagulation and fibrin deposition with intravascular trapping of RBCs and platelets (microangiopathy).

Consequently, these cases develop hemolytic anemia, thrombocytopenia and renal ischemia/insufficiency. Unlike DIC, microvascular injury and thrombosis in HUS is relatively localized to renal vasculature, though other organs, e.g. brain may be affected to some extent.

Pathologically, Thrombotic microangiopathy is the key finding on renal biopsy in HUS, characterized by:

• narrowing of glomerular capillaries due to swollen endothelium and intraluminal accumulation of blood cells/fibrin thrombi,

• accumulation of foamy fibrillar material in sub­endothelial spaces and mesangium,

• Pre-glomerular arteriolar narrowing with onion-skin appearance due to intimal thickening, and

• Patchy or extensive cortical necrosis.

Clinically, Typical HUS is usually seen in young children below 4 years of age during or within 5-10 days of an attack of acute bacillary diarrhea/dysentery.

Atypical HUS is more common in older children and usually presents with more insidious onset of hematuria, progressive renal insufficiency and severe hypertension. These cases have poorer prognosis with higher risk of developing chronic kidney disease.

Diagnosis rests on typical clinical picture in susceptible age group and combination of three essential laboratory findings, i.e.

1. Hemolytic peripheral smear with distorted erythro­cytes, schistocytes, and high reticulocyte count,

2. Thrombocytopenia, and

3. Acute renal failure with elevated BUN and S. creatinine.

Polymorphonuclear leukocytosis, microscopic hematuria and mild proteinuria is common. Interestingly, hypokalemia may be present in early HUS despite renal failure, due to GIT losses of potassium in diarrhea. Renal biopsy is diagnostic, though rarely indicated except in atypical HUS.

Treatment is largely supportive, including manage­ment of acute renal failure, hypertension, anemia and concurrent infections. Peritoneal dialysis may be necessary to prevent complications of renal failure. Platelet transfusion should be avoided despite low counts, as transfused platelets are rapidly consumed by the active coagulation and can worsen the disease. Plasmapheresis or Eculizumab — an anti-C5 antibody that inhibits complement activation, may be beneficial in atypical HUS.

Prognosis: While immediate mortality in adequately treated cases of typical HUS is lt;10%, 30-40% survivors are left with residual renal damage. Outcome is relatively poor in atypical cases or those with very young age, hypovolemic shock, positive family history, anuria gt;14 days, severe neurological involvement, gangrenous colitis and severe cortical necrosis on biopsy.

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