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

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 1985. Sazama et al. Transfusion 1990 Sep;30(7):583-90. 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

Hemoglobinuria Alpha-Beta dimers MW 34,000 -- small enough to be filtered by glomerulus

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

Prevention of ARF Volume repletion Alkalinization of urine Mannitol diuresis

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

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)

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

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%