1. Post-Diarrheal Hemolytic Uremic Syndrome (D+HUS)  Richard L. Siegler M.D.  Professor Emeritus  University of Utah School of Medicine

2. What is Post-Diarrheal Hemolytic Uremic Syndrome (D+HUS) and where did it come from ?  The syndrome includes: Acute kidney failure Hemolytic anemia Thrombocytopenia (low platelet count)  Most common cause of acute renal (kidney) failure in young children; also occurs in older children and adults

3. How did these otherwise harmless E. coli become such killers?  DNA from a Stx producing bacterium (Shigella dysenteriae type 1) transferred by bacteriophage to E. coli  This provided E. coli with genes to produce Shiga toxin (Stx), one of the most potent toxins known to man

4. Pathogenic Cascade; from diarrhea to dialysis  Chain of events: ingestion of Stx producing E. coli multiplication in bowel absorption of Stx into circulation

5. pathogenic cascade, cont.  Chain of events, cont.: attachment of Stx to receptors in kidney, and occasionally other organs movement of toxin into cells cell injury or death

6. pathogenic cascade, cont. the end result is:  hemorrhagic colitis (bloody diarrhea)  kidney injury, causing acute renal failure  damage of red blood cells causing anemia  trapping and destruction of platelets causing bleeding  occasional damage to other organs (brain, pancreas, heart, lungs, eyes)

7. Signs and Symptoms  diarrhea (usually bloody) with severe pain; can be mistaken for appendicitis  pallor  bruises  seizures and/or coma (occasionally)  little (oliguria) or no (anuria) urine  high blood pressure  pancreatic damage (diabetes)

8. Hospital course and Treatment  meticulous attention to salt and water balance  dialysis for kidney failure  blood transfusions for anemia  Platelet transfusions for bleeding  aggressive nutritional support (e.g., total parenteral nutrition [TPN])  treatment of high blood pressure  treatment of seizures

9. Outcomes  Death in 3-5%, due to: brain damage (stroke and/or brain swelling) bowel necrosis and perforation heart damage lung injury multiorgan injury (seen in most fatal cases)

10. outcomes, cont.  Those who survive may be left with: permanent kidney damage brain damage hypertension diabetes

11. Monitoring  Chronic kidney failure may occur decades later (due to hyperfiltration injury) most common in those who had prolonged kidney failure (oligoanuria) >10 days proteinurea (protein in the urine) is an early sign

12. monitoring, cont.  Hypertension may begin years later (in those with chronic kidney damage)  Diabetes can latter occur (in those with pancreatic injury)

13. Summary  D+ HUS is a life threatening complication of Stx producing E. coli  It occurs primarily in infants and young children, but also affects adults  Is fatal 3-5% of victims  Survivors (30-50%) are left with chronic kidney damage that can be progressive later in life  Life long monitoring is necessary