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Hemolytic Uremic Syndrome
Induced AKIh
From Pathogenesis to Bedside
Mohammed Abdel Gawad
Nephrologist
Kidney & Urology Cen...
To download the lecture
with full animations please
contact me on
drgawad@gmail.com
Visit
www.NephroTubeCNE.com
for more l...
 What is meant by Thrombotic Microangiopathy
(TMA)?
 What are the causes of TMA?
 What is the mechanism of TMA in HUS?
...
 What is meant by Thrombotic Microangiopathy
(TMA)?
 What are the causes of TMA?
 What is the mechanism of TMA in HUS?
...
What is meant by Thrombotic
Microangiopathy (TMA)?
Intraluminal platelet thrombosis
Thrombocytopenia
Microangiopathic hemo...
 What is meant by Thrombotic Microangiopathy
(TMA)?
 What are the causes of TMA?
 What is the mechanism of TMA in HUS?
...
What are the causes of
TMA?
,HIV
TTP/HUS
18
 What is meant by Thrombotic Microangiopathy
(TMA)?
 What are the causes of TMA?
 What is the mechanism of TMA in HUS?
...
What is the mechanism of
TMA in HUS?
Intraluminal platelet thrombosis
Thrombocytopenia
Microangiopathic hemolytic
anemia
C...
Intraluminal platelet thrombosis
Thrombocytopenia
Consumption of
platelets Shiga toxin HUS
Atypical HUS
Neuraminidase HUS
...
Intraluminal platelet thrombosis
Thrombocytopenia
Consumption of
platelets Shiga toxin HUS
Atypical HUS
Neuraminidase HUS
...
E. coli (STEC)
S. dysenteriae
`
watery or most
often bloody
diarrhea
`
Mead PS, Griffin PM. Lancet.1998;352:1207-1212.
Rug...
E. coli (STEC)
S. dysenteriae
watery or most
often bloody
diarrhea
Mead PS, Griffin PM. Lancet.1998;352:1207-1212.
Ruggene...
Shiga Toxin
Associated HUS
E. coli (STEC)
S. dysenteriae
watery or most
often bloody
diarrhea
Complement
activation by
alt...
Intraluminal platelet thrombosis
Thrombocytopenia
Consumption of
platelets Shiga toxin HUS
Atypical HUS
What is the mechan...
Neuraminidase
Associated HUS
In infants and children. Complicate pneumonia, or less
frequently, meningitis caused by S. pn...
Intraluminal platelet thrombosis
Thrombocytopenia
Consumption of
platelets Shiga toxin HUS
Atypical HUS
What is the mechan...
Atypical HUS
Caprioli J et al. Blood. 2006;108:1267-1279.
Manuelian T, et al. J Clin Invest. 2003;111:1181-1190.
Atypical ...
Atypical HUSAtypical HUS
14Marina Noris. N Engl J Med 2009;361:1676-87
Atypical HUS
Caprioli J et al. Blood. 2006;108:1267-1279.
Manuelian T, et al. J Clin Invest. 2003;111:1181-1190.
Noris M, ...
Atypical HUS
Caprioli J et al. Blood. 2006;108:1267-1279.
Manuelian T, et al. J Clin Invest. 2003;111:1181-1190.
Dragon-Du...
Atypical HUSAtypical HUS
12
Intraluminal platelet thrombosis
Thrombocytopenia
Consumption of
platelets Shiga toxin HUS
Atypical HUS
What is the mechan...
Intraluminal platelet thrombosis
Thrombocytopenia
Microangiopathic hemolytic
anemia
Consumption of
platelets
Hemolysis, An...
HUS – MAHA
11
Pathogenesis – Pathology
Relationship
11
David Kavanagh. F1000Prime Reports 2014, 6:119
 What is meant by Thrombotic Microangiopathy
(TMA)?
 What are the causes of TMA?
 What is the mechanism of TMA in HUS?
...
Marie Scully et al. British Journal
of Haematology, 2012, 158, 323–
335.
,HIV
DD of
thrombocytopenia
& MAHA
Systematic App...
Marie Scully et al. British Journal
of Haematology, 2012, 158, 323–
335.
Systematic Approach
of Diagnosis
Step 1 –
Exclude...
Piero Ruggenenti, Comprehensive
Clinical Nephrology. 4th
edition,
chapter 28, p353
Systematic Approach
of Diagnosis
Step 1...
- Marie Scully et al. British Journal of Haematology, 2012, 158, 323–335.
- Patton JF et al. Am J Hematol. 1994;47:94-99.
...
- Marie Scully et al. British Journal of Haematology, 2012, 158, 323–335.
- Patton JF et al. Am J Hematol. 1994;47:94-99.
...
Systematic Approach
of Diagnosis
Step 3 –
Coagulation Profile
Step 4 – Exclude other causes
9
Systematic Approach of
Diagn...
Systematic Approach
of Diagnosis
Step 4 – Exclude other causes
8
Systematic Approach of
Diagnosis
DD Suggestive Criteria
M...
Systematic Approach
of Diagnosis
Step 4 – Exclude other causes
,HIV
7
Systematic Approach of
Diagnosis
Systematic Approach
of Diagnosis
Step 4 – Exclude other causes
7
Systematic Approach of
Diagnosis
Systematic Approach
of Diagnosis
Step 4 – Exclude other causes
• TMA has been reported in
association with acute pancreati...
Systematic Approach
of Diagnosis
Step 5 –
TTP vs HUS
Shiga toxin-
HUS
Neuraminidase
-HUS
Atypical HUS TTP
7
Systematic App...
Systematic Approach
of Diagnosis
Shiga toxin-
HUS
Neuraminidase
-HUS
- Less than 2 years old
- Respiratory distress,
neuro...
Systematic Approach
of Diagnosis
Shiga toxin-
HUS
Neuraminidase
-HUS
- Less than 2 years old
- Respiratory distress,
neuro...
Systematic Approach
of Diagnosis
Neuraminidase
-HUS
- Less than 2 years old
- Respiratory distress,
neurologic
involvement...
Systematic Approach
of Diagnosis
Step 5 –
TTP vs HUS
Shiga toxin-
HUS
Neuraminidase
-HUS
Atypical HUS TTP
6
Systematic App...
Systematic Approach
of Diagnosis
Atypical HUS TTP
Step 5 – TTP vs HUS
Difficult to distinguish on clinical grounds only
Mo...
Systematic Approach
of Diagnosis
Atypical HUS TTP
Step 5 – TTP vs HUS
Difficult to distinguish on clinical grounds only
Di...
Systematic Approach
of Diagnosis
Atypical HUS TTP
Step 5 – TTP vs HUS
Difficult to distinguish on clinical grounds only
Mo...
Systematic Approach
of Diagnosis
Step 1: Exclusion of drugs
Step 2: Exclusion of Autoimmune hemolysis
Step 3: Coagulation ...
 What is meant by Thrombotic Microangiopathy
(TMA)?
 What are the causes of TMA?
 What is the mechanism of TMA in HUS?
...
Shiga Toxin
Associated HUS
E. coli (STEC)
S. dysenteriae
watery or most
often bloody
diarrhea
Ruggenenti P, Remuzzi G.Lanc...
Shiga Toxin Associated HUS
Treatment
Generally Supportive (including RRT if required)
No role for Anticoagulation
No role ...
Generally Supportive (including RRT if required)
No role for Antibiotics except:
1.Patients presenting with bacteremia
2.H...
Generally Supportive (including RRT if required)
Is there a role for plasma exchange?
No prospective RCTs are available
AD...
Atypical HUS
Caprioli J et al. Blood. 2006;108:1267-1279.
Manuelian T, et al. J Clin Invest. 2003;111:1181-1190.
2
Genetic...
Atypical HUS Treatment
2
When to start? within 24 hours of diagnosis
Frequency: daily initially, then determined by clinic...
Atypical HUS Treatment
Plasma exchange (1 to 2 plasma volumes/day)
vs Plasma infusion (20 to 30 ml/kg/day)
Plasma Exchange...
Atypical HUSAtypical HUS
Marina Noris. N Engl J Med 2009;361:1676-87
M. Kathryn Liszewski. The Rheumatologist, February 20...
Atypical HUSAtypical HUS
Marina Noris. N Engl J Med 2009;361:1676-87
M. Kathryn Liszewski. The Rheumatologist, February 20...
Atypical HUS Treatment
Immunosuppressants (corticosteroids
and azathioprine or mycophenolate mofetil)
combined with plasma...
Atypical HUS Treatment
Licht C et al. J Am Soc Nephrol. 2011;22:197A.
Greenbaum LA et al. J Am Soc Nephrol. 2011;22:197A.
...
Atypical HUSAtypical HUS
0
Living related donation is contraindicated given the high risk of
recurrence
Living related don...
Atypical HUSAtypical HUS
0
HUS Treatment
0
STEC - HUS Atypical HUS
• General supportive
• IV isotonic hydration
• No anticoagulation
• No antimotilit...
First Reported HUS Cases
Gasser C, Gautier E, Steck A, et al. Schweiz Med Wochenschr. 1955;85:905-
909.
0
Gawad
www.NephroTube CNE.com
Thank You
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Hemolytic Uremic Syndrome Induced AKI (From Pathogenesis to Bedside) - Dr. Gawad

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Hemolytic Uremic Syndrome Induced AKI (From Pathogenesis to Bedside) - Dr. Gawad

  1. 1. Hemolytic Uremic Syndrome Induced AKIh From Pathogenesis to Bedside Mohammed Abdel Gawad Nephrologist Kidney & Urology Center (KUC) Alexandria – EGY drgawad@gmail.com
  2. 2. To download the lecture with full animations please contact me on drgawad@gmail.com Visit www.NephroTubeCNE.com for more lectures
  3. 3.  What is meant by Thrombotic Microangiopathy (TMA)?  What are the causes of TMA?  What is the mechanism of TMA in HUS?  What is the diagnostic approach of HUS & TMA?  What are the treatment protocols of HUS? 19 Talk Outline
  4. 4.  What is meant by Thrombotic Microangiopathy (TMA)?  What are the causes of TMA?  What is the mechanism of TMA in HUS?  What is the diagnostic approach of HUS & TMA?  What are the treatment protocols of HUS? 19 Talk Outline
  5. 5. What is meant by Thrombotic Microangiopathy (TMA)? Intraluminal platelet thrombosis Thrombocytopenia Microangiopathic hemolytic anemia Consumption of platelets Hemolysis, Anemia, ↑LDH & Bilirubin 119
  6. 6.  What is meant by Thrombotic Microangiopathy (TMA)?  What are the causes of TMA?  What is the mechanism of TMA in HUS?  What is the diagnostic approach of HUS & TMA?  What are the treatment protocols of HUS? Talk Outline 19
  7. 7. What are the causes of TMA? ,HIV TTP/HUS 18
  8. 8.  What is meant by Thrombotic Microangiopathy (TMA)?  What are the causes of TMA?  What is the mechanism of TMA in HUS?  What is the diagnostic approach of HUS & TMA?  What are the treatment protocols of HUS? QuestionsTalk Outline 18
  9. 9. What is the mechanism of TMA in HUS? Intraluminal platelet thrombosis Thrombocytopenia Microangiopathic hemolytic anemia Consumption of platelets Hemolysis, Anemia, ↑LDH & Bilirubin 18
  10. 10. Intraluminal platelet thrombosis Thrombocytopenia Consumption of platelets Shiga toxin HUS Atypical HUS Neuraminidase HUS What is the mechanism of TMA in TTP-HUS? What is the mechanism of TMA in HUS? 18
  11. 11. Intraluminal platelet thrombosis Thrombocytopenia Consumption of platelets Shiga toxin HUS Atypical HUS Neuraminidase HUS What is the mechanism of TMA in TTP-HUS? What is the mechanism of TMA in HUS? 18
  12. 12. E. coli (STEC) S. dysenteriae ` watery or most often bloody diarrhea ` Mead PS, Griffin PM. Lancet.1998;352:1207-1212. Ruggenenti P, Remuzzi G.Lancet. 2011;378:1057-1058. Shiga Toxin Associated HUS E.Coli: Mostly the serotype O157:H7, but also other serotypes, such as O111:H8, O103:H2, O123, O26, O145, and the O104:H4 strain of the recent German outbreak 18
  13. 13. E. coli (STEC) S. dysenteriae watery or most often bloody diarrhea Mead PS, Griffin PM. Lancet.1998;352:1207-1212. Ruggenenti P, Remuzzi G.Lancet. 2011;378:1057-1058. Shiga Toxin Associated HUS Shiga Toxin Associated HUS 17
  14. 14. Shiga Toxin Associated HUS E. coli (STEC) S. dysenteriae watery or most often bloody diarrhea Complement activation by alternative pathway: High plasma levels of complement activation products Bb and C5b-9 were measured in children with STEC-HUS Morigi M et al. Blood. 2001;98:1828-1835. Morigi M et al. J Immunol. 2011;187:172-180. Shiga Toxin Associated HUS 16
  15. 15. Intraluminal platelet thrombosis Thrombocytopenia Consumption of platelets Shiga toxin HUS Atypical HUS What is the mechanism of TMA in TTP-HUS? What is the mechanism of TMA in HUS? Neuraminidase HUS Toxin binds endothelium 16
  16. 16. Neuraminidase Associated HUS In infants and children. Complicate pneumonia, or less frequently, meningitis caused by S. pneumoniae erythrocytes, platelets, glomerular cells Polyagglutination Brandt J, Wong C, Mihm S, et al. Pediatrics. 2002;110:371-376. 8 Thomsen-Friedenreich antigen Coomb’s +ve
  17. 17. Intraluminal platelet thrombosis Thrombocytopenia Consumption of platelets Shiga toxin HUS Atypical HUS What is the mechanism of TMA in TTP-HUS? What is the mechanism of TMA in HUS? Neuraminidase HUS Toxin binds endothelium N’ase 15
  18. 18. Atypical HUS Caprioli J et al. Blood. 2006;108:1267-1279. Manuelian T, et al. J Clin Invest. 2003;111:1181-1190. Atypical HUS Genetic mutation 14
  19. 19. Atypical HUSAtypical HUS 14Marina Noris. N Engl J Med 2009;361:1676-87
  20. 20. Atypical HUS Caprioli J et al. Blood. 2006;108:1267-1279. Manuelian T, et al. J Clin Invest. 2003;111:1181-1190. Noris M, N Engl J Med. 2009;361:1676-1687. Atypical HUS Genetic mutation Precipitants of aHUS: •Non-enteric bacterial and viral Infections •Immunotherapeutic agents (e.g., cyclosporine, tacrolimus) •Malignant hypertension •Transplantation •Pregnancy About 50% of patients with sporadic aHUS show no clear trigger (idiopathic HUS) 13
  21. 21. Atypical HUS Caprioli J et al. Blood. 2006;108:1267-1279. Manuelian T, et al. J Clin Invest. 2003;111:1181-1190. Dragon-Durey et al. J Am Soc Nephrol. 2005;16:555-563. Atypical HUS Genetic mutation Acquired defects of CFH function (inhibitory antibodies), reported in 5% to 10% of aHUS 13
  22. 22. Atypical HUSAtypical HUS 12
  23. 23. Intraluminal platelet thrombosis Thrombocytopenia Consumption of platelets Shiga toxin HUS Atypical HUS What is the mechanism of TMA in TTP-HUS? What is the mechanism of TMA in HUS? Neuraminidase HUS Toxin binds endothelium N’ase Alternative Complement 12
  24. 24. Intraluminal platelet thrombosis Thrombocytopenia Microangiopathic hemolytic anemia Consumption of platelets Hemolysis, Anemia, ↑LDH & Bilirubin What is the mechanism of TMA in HUS? Microangiopathic hemolytic anemia Hemolysis, Anemia, ↑LDH & Bilirubin 12
  25. 25. HUS – MAHA 11
  26. 26. Pathogenesis – Pathology Relationship 11 David Kavanagh. F1000Prime Reports 2014, 6:119
  27. 27.  What is meant by Thrombotic Microangiopathy (TMA)?  What are the causes of TMA?  What is the mechanism of TMA in HUS?  What is the diagnostic approach of HUS & TMA?  What are the treatment protocols of HUS? QuestionsTalk Outline 11
  28. 28. Marie Scully et al. British Journal of Haematology, 2012, 158, 323– 335. ,HIV DD of thrombocytopenia & MAHA Systematic Approach of Diagnosis 11
  29. 29. Marie Scully et al. British Journal of Haematology, 2012, 158, 323– 335. Systematic Approach of Diagnosis Step 1 – Exclude Drugs Systematic Approach of Diagnosis 10
  30. 30. Piero Ruggenenti, Comprehensive Clinical Nephrology. 4th edition, chapter 28, p353 Systematic Approach of Diagnosis Step 1 – Exclude Drugs Systematic Approach of Diagnosis 10
  31. 31. - Marie Scully et al. British Journal of Haematology, 2012, 158, 323–335. - Patton JF et al. Am J Hematol. 1994;47:94-99. Systematic Approach of Diagnosis Step 2 – Autoimmune Hemolysis Step 3 10 Systematic Approach of Diagnosis
  32. 32. - Marie Scully et al. British Journal of Haematology, 2012, 158, 323–335. - Patton JF et al. Am J Hematol. 1994;47:94-99. Systematic Approach of Diagnosis Step 2 – Autoimmune Hemolysis Step 3 10 Systematic Approach of Diagnosis
  33. 33. Systematic Approach of Diagnosis Step 3 – Coagulation Profile Step 4 – Exclude other causes 9 Systematic Approach of Diagnosis
  34. 34. Systematic Approach of Diagnosis Step 4 – Exclude other causes 8 Systematic Approach of Diagnosis DD Suggestive Criteria Malignant Hypertension • Systolic BP >200 mmHg, diastolic BP >130 mmHg. • MAHA and thrombocytopenia resolves with BP management. Pre- eclampsia • New BP elevation and proteinuria after 20 weeks of gestation in a pregnant woman. Sepsis • Hypotension • More pronounced fever • Raised white count with left shift. • Blood cultures might be positive. Pregnancy • Must be excluded. Autoimmune Disease • ANA, RF, antiDNA, ACLA, lupus anticoagulant
  35. 35. Systematic Approach of Diagnosis Step 4 – Exclude other causes ,HIV 7 Systematic Approach of Diagnosis
  36. 36. Systematic Approach of Diagnosis Step 4 – Exclude other causes 7 Systematic Approach of Diagnosis
  37. 37. Systematic Approach of Diagnosis Step 4 – Exclude other causes • TMA has been reported in association with acute pancreatitis. • Sometimes a number of days after resolution of pancreatitis. • All patients were successfully treated with PEX and corticosteroids (McDonald et al, 2009). An association between thrombocytopenia and thyrotoxicosis has been reported 7 Systematic Approach of Diagnosis
  38. 38. Systematic Approach of Diagnosis Step 5 – TTP vs HUS Shiga toxin- HUS Neuraminidase -HUS Atypical HUS TTP 7 Systematic Approach of Diagnosis
  39. 39. Systematic Approach of Diagnosis Shiga toxin- HUS Neuraminidase -HUS - Less than 2 years old - Respiratory distress, neurologic involvement, and coma. Mead PS, Griffin PM. Lancet. 1998;352:1207-1212. Step 5 – TTP vs HUS 6 Systematic Approach of Diagnosis - Occurs primarily in children, (except in epidemics with any age) -Watery or bloody diarrhoea. - Stool Culture: detection of E. coli O157:H7 and other STEC and their products in stool cultures (sorbitol- containing MacConkey agar - SMAC)
  40. 40. Systematic Approach of Diagnosis Shiga toxin- HUS Neuraminidase -HUS - Less than 2 years old - Respiratory distress, neurologic involvement, and coma. Mead PS, Griffin PM. Lancet. 1998;352:1207-1212. Step 5 – TTP vs HUS 6 Systematic Approach of Diagnosis - Occurs primarily in children, (except in epidemics with any age) -Watery or bloody diarrhoea. - Stool Culture: detection of E. coli O157:H7 and other STEC and their products in stool cultures (sorbitol- containing MacConkey agar - SMAC)
  41. 41. Systematic Approach of Diagnosis Neuraminidase -HUS - Less than 2 years old - Respiratory distress, neurologic involvement, and coma. Mead PS, Griffin PM. Lancet. 1998;352:1207-1212. Step 5 – TTP vs HUS 6 Systematic Approach of Diagnosis
  42. 42. Systematic Approach of Diagnosis Step 5 – TTP vs HUS Shiga toxin- HUS Neuraminidase -HUS Atypical HUS TTP 6 Systematic Approach of Diagnosis
  43. 43. Systematic Approach of Diagnosis Atypical HUS TTP Step 5 – TTP vs HUS Difficult to distinguish on clinical grounds only Moschcowitz E. Mt Sinai J Med. 2003;70:352-355. 5 Systematic Approach of Diagnosis
  44. 44. Systematic Approach of Diagnosis Atypical HUS TTP Step 5 – TTP vs HUS Difficult to distinguish on clinical grounds only Differential diagnosis of aHUS is made on exclusion: • Of infections by STEC or neuraminidase - producing S.pneumoniae, • Of ADAMTS13 deficiency, • Of Systemic-associated diseases 5 Systematic Approach of Diagnosis
  45. 45. Systematic Approach of Diagnosis Atypical HUS TTP Step 5 – TTP vs HUS Difficult to distinguish on clinical grounds only Moschcowitz E. Mt Sinai J Med. 2003;70:352-355. Eknoyan G, Riggs SA. Am J Nephrol. 1986;6:117-131. 5 Systematic Approach of Diagnosis
  46. 46. Systematic Approach of Diagnosis Step 1: Exclusion of drugs Step 2: Exclusion of Autoimmune hemolysis Step 3: Coagulation Profile Step 4: Exclusion of other systemic causes Step 5: TTP vs HUS? 5 Systematic Approach of Diagnosis Diagnosis Message
  47. 47.  What is meant by Thrombotic Microangiopathy (TMA)?  What are the causes of TMA?  What is the mechanism of TMA in HUS?  What is the diagnostic approach of HUS & TMA?  What are the treatment protocols of HUS? Questions 4 Talk Outline
  48. 48. Shiga Toxin Associated HUS E. coli (STEC) S. dysenteriae watery or most often bloody diarrhea Ruggenenti P, Remuzzi G.Lancet. 2011;378:1057-1058. Morigi M et al. J Immunol. 2011;187:172-180. 4 Complement activation by alternative pathway: High plasma levels of complement activation products Bb and C5b-9 were measured in children with STEC-HUS
  49. 49. Shiga Toxin Associated HUS Treatment Generally Supportive (including RRT if required) No role for Anticoagulation No role for Antitimotility agents 4 IV isotonic volume expansion (as soon as an E. coli O157:H7 infection is suspected), limit the severity of AKI and the need for RRT Ake JA et al. Pediatrics. 2005;115:e673-e680
  50. 50. Generally Supportive (including RRT if required) No role for Antibiotics except: 1.Patients presenting with bacteremia 2.HUS, hemorrhagic colitis and HUS caused by Shigella dysentery type 1 3.Azithromycin had some benefit on the duration of bacterial shedding in adult patients from the German O104:H4 epidemic Shiga Toxin Associated HUS Treatment 3 Nitschke M et al. JAMA. 2012;307:1046-1052. Van Dyck M, et al. Pediatr Nephrol. 2004;19:688-690.
  51. 51. Generally Supportive (including RRT if required) Is there a role for plasma exchange? No prospective RCTs are available ADULT patients with severe AKI and CNS involvement plasma therapy may decrease overall mortality of STEC O157:H7–associated HUS. Dundas S et al. Lancet. 1999;354:1327-1330. Carter AO et al. N Engl J Med. 1987;317:1496-1500. Shiga Toxin Associated HUS Treatment 3
  52. 52. Atypical HUS Caprioli J et al. Blood. 2006;108:1267-1279. Manuelian T, et al. J Clin Invest. 2003;111:1181-1190. 2 Genetic mutation Acquired defects of CFH function (inhibitory antibodies), reported in 5% to 10% of aHUS
  53. 53. Atypical HUS Treatment 2 When to start? within 24 hours of diagnosis Frequency: daily initially, then determined by clinical response Plasma exchange (1 to 2 plasma volumes/day) vs Plasma infusion (20 to 30 ml/kg/day)
  54. 54. Atypical HUS Treatment Plasma exchange (1 to 2 plasma volumes/day) vs Plasma infusion (20 to 30 ml/kg/day) Plasma Exchange is superior to Infusion: 1.Supply larger amounts of plasma while avoiding fluid overload. 2.Removal of mutant CFH. 3.Remove anti-CFH antibodies, but the effect is usually transient. Noris M, Remuzzi G. N Engl J Med. 2009;361:1676-1687. Dragon-Durey MA, et al. J Am Soc Nephrol. 2005;16:555-563. 2
  55. 55. Atypical HUSAtypical HUS Marina Noris. N Engl J Med 2009;361:1676-87 M. Kathryn Liszewski. The Rheumatologist, February 2010 1
  56. 56. Atypical HUSAtypical HUS Marina Noris. N Engl J Med 2009;361:1676-87 M. Kathryn Liszewski. The Rheumatologist, February 2010 MCP is expressed on the surface of all cells (except RBC) 1
  57. 57. Atypical HUS Treatment Immunosuppressants (corticosteroids and azathioprine or mycophenolate mofetil) combined with plasma exchange allowed long- term dialysis-free survival in 60% to 70% of patients. Dragon-Durey MA et al. J Am Soc Nephrol. 2010;21:2180-2187. Plasma exchange 1
  58. 58. Atypical HUS Treatment Licht C et al. J Am Soc Nephrol. 2011;22:197A. Greenbaum LA et al. J Am Soc Nephrol. 2011;22:197A. 1 Atypical HUS Treatment Duration of therapy?? Cost??
  59. 59. Atypical HUSAtypical HUS 0 Living related donation is contraindicated given the high risk of recurrence Living related donation may be risky to donors because uninephrectomy may precipitate aHUS in complement gene mutation carriers.
  60. 60. Atypical HUSAtypical HUS 0
  61. 61. HUS Treatment 0 STEC - HUS Atypical HUS • General supportive • IV isotonic hydration • No anticoagulation • No antimotility drugs • No antibiotics (except some situations) • ??? PEX • Plasma Therapy (PEX is better) + Immunosuppressives • Eculizmab • Renal ± Liver Transplantation Treatment Message
  62. 62. First Reported HUS Cases Gasser C, Gautier E, Steck A, et al. Schweiz Med Wochenschr. 1955;85:905- 909. 0
  63. 63. Gawad www.NephroTube CNE.com Thank You

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