1. Acute renal failure from hemolytic transfusion reactions
Brad Weaver, MD
9/25/07

2. Acute hemolytic transfusion reaction
ABO incompatability is the major cause of death from transfusion
125 deaths reported to FDA due to ABO incompatable transfusion from 1976 to Sazama et al. Transfusion 1990 Sep;30(7):
IgM anti-A and anti-B fix complement  rapid intravascular hemolysis
Acute renal failure from ATN
DIC
Shock
Hyperkalemia
Renal failure can be caused by direct toxicity of hemoglobin and by renal ischemia from shock

3. Hemoglobinuria
Alpha-Beta dimers MW 34, small enough to be filtered by glomerulus

4. Proposed mechanisms of renal injury
1. Obstruction of tubules with heme pigment casts
2. Oxidative damage to proximal tubule by released free iron
Low FENa characteristic

6. Prevention of ARF Volume repletion Alkalinization of urine
Mannitol diuresis

7. Alkalinization of urine and mannitol
Hemoglobin less likely to precipitate with Tamm-Horsfall protein in alkaline urine
Alkalinization stabilizes reactive iron species
Mannitol acts as an osmotic diuretic, dilates renal vasculature, and is an antioxidant

8. A retrospective series Brown et al. J Trauma 56(6) 2004
Series of 382 patients with serum CK concentration >5000 U/L, 154 (40 percent) were treated with bicarbonate and mannitol
No statistically significant difference in the incidence of:
renal failure as defined by Cr >2.0 (22 versus 18 percent)
dialysis (7 versus 6 percent)
death (15 versus 18 percent)

11. A case report Amyot et al. Intensive Care Med. 25. 1999
A 30yo man with myoglobin-induced renal failure was treated with CVVH for 33h
Blood flow 150 mL/min, ultrafiltration rate 2 to 3L/h
Serum myoglobin (MW 17,000) concentration decreased from 92,000 ug/L to 28,600 ug/L after 18h
Required HD for 25 days and eventually recovered normal renal function

13. Preventing hemolysis – recombinant complement receptor 1 Yazdanbakhsh et al. Blood 101 (12) 2003
Complement receptor 1 (CR1) – transmembrane protein that inhibits C3 and C5 convertases and cofactor for serum protease 1
Mouse study: recombinant soluble form of CR1 inhibited complement activation in mice with pre-existing anti-A transfused with human group A RBCs
RBC survival increased by 50%