Advance Targeted Transfusion in Anemic Cardiac Surgical Patients for Kidney Protection: An Unblinded Randomized Pilot Clinical Trial

Introduction: Acute kidney injury (AKI) is a serious complication of cardiac surgery, and preoperative anemia and perioperative erythrocyte transfusion are important risk factors. Prophylactic erythrocyte transfusion in anemic patients may, therefore, protect against AKI. Methods: In this unblinded, parallel-group, randomized pilot trial, 60 anemic patients (hemoglobin 10–12 g/dL) undergoing cardiac surgery with cardiopulmonary bypass were randomized (1:1) to prophylactic transfusion (2 units of erythrocytes transfused 1 to 2 days before surgery (n = 29) or standard of care (transfusions as indicated; n = 31). Between-group differences in severity of perioperative anemia, transfusion, and AKI (more than 25% drop in estimated glomerular filtration rate) were measured. The relationships between transfusion, iron levels, and AKI were also measured. Results: Perioperative anemia and erythrocyte transfusions were lower in the prophylactic transfusion group – median (25th, 75th percentiles) for nadir hemoglobin was 8.3 (7.9, 9.1) versus 7.6 (6.9, 8.2) g/dL (P = 0.0008) and for transfusion was 0 (0, 2) versus 2 (1, 4) units (P = 0.0002) – but between-group AKI rates were comparable (11 patients per group). In 35 patients with iron studies, perioperative transfusions were directly related to postoperative transferrin saturation (correlation coefficient 0.6; P = 0.0002), and high (more than 80%) transferrin saturation was associated with AKI (5/5 vs. 8/30; P = 0.005), implicating transfusion-related iron overload as a cause of AKI. Conclusions: In anemic patients, prophylactic erythrocyte transfusion reduces perioperative anemia and erythrocyte transfusions, and may reduce plasma iron levels. Adequately powered studies assessing the effect of this intervention on AKI are warranted.

[1]  A. Renzulli,et al.  Acute kidney injury: a relevant complication after cardiac surgery. , 2011, Annals of Thoracic Surgery.

[2]  Christopher T. Chan,et al.  Influence of Erythrocyte Transfusion on the Risk of Acute Kidney Injury after Cardiac Surgery Differs in Anemic and Nonanemic Patients , 2011, Anesthesiology.

[3]  Claudio Ronco,et al.  Classification and staging of acute kidney injury: beyond the RIFLE and AKIN criteria , 2011, Nature Reviews Nephrology.

[4]  E. Hod,et al.  Harmful effects of transfusion of older stored red blood cells: iron and inflammation , 2011, Transfusion.

[5]  G. Angelini,et al.  Pharmacological therapies for the prevention of acute kidney injury following cardiac surgery: a systematic review , 2011, Heart Failure Reviews.

[6]  M. Caputo,et al.  Occult renal dysfunction: a mortality and morbidity risk factor in coronary artery bypass grafting surgery. , 2011, The Journal of thoracic and cardiovascular surgery.

[7]  H. Schaff,et al.  Clinical accuracy of RIFLE and Acute Kidney Injury Network (AKIN) criteria for acute kidney injury in patients undergoing cardiac surgery , 2011, Critical care.

[8]  A. Köttgen,et al.  Prevalence of kidney disease in anaemia differs by GFR-estimating method: the Third National Health and Nutrition Examination Survey (1988-94). , 2010, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[9]  S. McCluskey,et al.  The Influence of Perioperative Coagulation Status on Postoperative Blood Loss in Complex Cardiac Surgery: A Prospective Observational Study , 2010, Anesthesia and analgesia.

[10]  Ning Zhang,et al.  Transfusion of red blood cells after prolonged storage produces harmful effects that are mediated by iron and inflammation. , 2010, Blood.

[11]  R. Bellomo,et al.  Novel biomarkers, oxidative stress, and the role of labile iron toxicity in cardiopulmonary bypass-associated acute kidney injury. , 2010, Journal of the American College of Cardiology.

[12]  Jennifer L. Turi,et al.  Iron overload following red blood cell transfusion and its impact on disease severity. , 2009, Biochimica et biophysica acta.

[13]  P. Nickerson,et al.  Mass spectrometry-based proteomic analysis of urine in acute kidney injury following cardiopulmonary bypass: a nested case-control study. , 2009, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[14]  S. McCluskey,et al.  Acute Kidney Injury After Cardiac Surgery: Focus on Modifiable Risk Factors , 2009, Circulation.

[15]  Leen Vercaemst,et al.  Hemolysis in cardiac surgery patients undergoing cardiopulmonary bypass: a review in search of a treatment algorithm. , 2008, The journal of extra-corporeal technology.

[16]  Jeremiah R. Brown,et al.  Long-term survival after cardiac surgery is predicted by estimated glomerular filtration rate. , 2008, The Annals of thoracic surgery.

[17]  M. Swaminathan,et al.  Acute kidney injury and chronic kidney disease after cardiac surgery. , 2008, Advances in chronic kidney disease.

[18]  W. D. de Grip,et al.  Survival of red blood cells after transfusion: a comparison between red cells concentrates of different storage periods , 2008, Transfusion.

[19]  John A Kellum,et al.  Costs and outcomes of acute kidney injury (AKI) following cardiac surgery. , 2008, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[20]  D. Wijeysundera,et al.  Risk Associated With Preoperative Anemia in Cardiac Surgery: A Multicenter Cohort Study , 2008, Circulation.

[21]  T. Yau,et al.  Variability and predictability of large‐volume red blood cell transfusion in cardiac surgery: a multicenter study , 2007, Transfusion.

[22]  Robert M Califf,et al.  Evolution of adverse changes in stored RBCs , 2007, Proceedings of the National Academy of Sciences.

[23]  I. C. Tudor,et al.  Impact of Preoperative Anemia on Outcome in Patients Undergoing Coronary Artery Bypass Graft Surgery , 2007, Circulation.

[24]  C. Ince,et al.  The impact of storage on red cell function in blood transfusion. , 2007, Best practice & research. Clinical anaesthesiology.

[25]  R. Bellomo,et al.  Defining and classifying acute renal failure: from advocacy to consensus and validation of the RIFLE criteria , 2007, Intensive Care Medicine.

[26]  C. Ince,et al.  Acute decrease in renal microvascular PO2 during acute normovolemic hemodilution. , 2007, American journal of physiology. Renal physiology.

[27]  D. Fergusson,et al.  Clinical consequences of red cell storage in the critically ill , 2006, Transfusion.

[28]  T. Ganz,et al.  Regulation of iron metabolism by hepcidin. , 2006, Annual review of nutrition.

[29]  Jeffrey L. Apfelbaum,et al.  Practice Guidelines for Perioperative Blood Transfusion and Adjuvant Therapies: An Updated Report by the American Society of Anesthesiologists Task Force on Perioperative Blood Transfusion and Adjuvant Therapies , 2006, Anesthesiology.

[30]  Andrew D. Rosenberg,et al.  Practice guidelines for perioperative blood transfusion and adjuvant therapies: An updated report by the American Society of Anesthesiologists Task Force on perioperative blood transfusion and adjuvant therapies , 2006 .

[31]  M. Ranucci,et al.  Oxygen delivery during cardiopulmonary bypass and acute renal failure after coronary operations. , 2005, The Annals of thoracic surgery.

[32]  M. Nangaku Chronic hypoxia and tubulointerstitial injury: a final common pathway to end-stage renal failure. , 2005, Journal of the American Society of Nephrology : JASN.

[33]  M. Okusa,et al.  Acute kidney injury associated with cardiac surgery. , 2005, Clinical journal of the American Society of Nephrology : CJASN.

[34]  R. Habib,et al.  Role of hemodilutional anemia and transfusion during cardiopulmonary bypass in renal injury after coronary revascularization: Implications on operative outcome* , 2005, Critical care medicine.

[35]  V. Rao,et al.  Hemodilution during cardiopulmonary bypass is an independent risk factor for acute renal failure in adult cardiac surgery. , 2005, The Journal of thoracic and cardiovascular surgery.

[36]  L. Bachmann,et al.  Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: a prospective cohort study. , 2004, Journal of the American Society of Nephrology : JASN.

[37]  G. Buonocore,et al.  Iron release, oxidative stress and erythrocyte ageing. , 2002, Free radical biology & medicine.

[38]  J. Parkkinen,et al.  Bleomycin-detectable iron assay for non-transferrin-bound iron in hematologic malignancies. , 2002, Clinical chemistry.

[39]  W. Breuer,et al.  The importance of non-transferrin bound iron in disorders of iron metabolism. , 2000, Transfusion science.

[40]  O. Sommerburg,et al.  Oxidative stress in anemia. , 2000, Clinical nephrology.

[41]  K E Hammermeister,et al.  Independent association between acute renal failure and mortality following cardiac surgery. , 1998, The American journal of medicine.

[42]  J. Pepper,et al.  Sequential oxidative damage, and changes in iron-binding and iron-oxidising plasma antioxidants during cardiopulmonary bypass surgery. , 1994, Free radical research.

[43]  D. Harris,et al.  Increased nephron oxygen consumption: potential role in progression of chronic renal disease. , 1994, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[44]  A. Heaton,et al.  In vivo regeneration of red cell 2, 3‐diphosphoglycerate following transfusion of DPG‐depleted AS‐1, AS‐3 and CPDA‐1 red cells , 1989, British journal of haematology.

[45]  M. H. Gault,et al.  Prediction of creatinine clearance from serum creatinine. , 1975, Nephron.

[46]  L. Watering,et al.  Red cell storage and prognosis , 2011, Vox sanguinis.

[47]  P. Lundberg,et al.  Hepcidin, interleukin-6 and hematological iron markers in males before and after heart surgery. , 2009, The Journal of nutritional biochemistry.

[48]  E. Kurtoğlu,et al.  Effect of iron supplementation on oxidative stress and antioxidant status in iron-deficiency anemia , 2007, Biological Trace Element Research.

[49]  P. Persson,et al.  Oxygen and renal hemodynamics in the conscious rat. , 2000, Journal of the American Society of Nephrology : JASN.