Red blood cell transfusion and furosemide in cardiac surgery: friend or foe?

Acute kidney injury (AKI) is one of the most common complications of cardiac surgery and even when the injury is relatively modest it is independently associated with both a high morbidity and mortality. The pathogenesis of AKI in cardiac surgery (CS-AKI) is complex and incompletely understood with aetiological features that are both common to other types of AKI as well as some specific features. The mechanisms include action of exogenous and endogenous toxins, metabolic factors, ischaemia-reperfusion injury, neurohormonal activation, inflammation and oxidative stress. Each may play a role in the pathogenesis of CS-AKI throughout the process but are not necessarily temporally related. Numerous therapies for the prevention of AKI have been tested but none have been proven particularly effective. This lack of effective therapies prompted Dr Vellinga and colleagues to try and identify modifiable risk factors for reducing AKI after cardiac surgery as published in this issue of The Netherlands Journal of Medicine. The authors performed a single-centre retrospective analysis in 565 adult patients who underwent coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). Serum creatinine (SCr) was determined at admission and at 24-hour intervals for a minimum of 48 hours and a maximum of seven days. Unfortunately urine output and fluid balance were not recorded. AKI was determined by the modified AKIN criteria employing only the serum creatinine criteria. Eighty-three patients were diagnosed with AKI, of which 74 (89%) were classified as AKIN I, 4 (5%) patients AKIN II, 3 (4%) patients AKIN III with 2 (2%) patients receiving renal replacement therapy (RRT). Despite the impressively low rate of CS-AKI both mortality rate and length of hospital stay were not reported. Based on their multivariate analysis findings the authors concluded that intraoperative and postoperative red blood cell (RBC) transfusion as well as administration of furosemide played a significant role in the development of AKI. These findings are in keeping with some other studies and as such are not unique. Numerous studies have reported renal risk factors derived in a multivariate fashion from larger cohorts of patients undergoing cardiac surgical procedures. For example, in 2009 Karkouti et al. performed a large multicentre study in 3500 patients who underwent cardiac surgery with CPB using the modified RIFLE criteria (GFR criteria only) to define AKI. Although the most predictive risk factors were CPB duration and intra-aortic balloon pump before surgery, three potentially modifiable and interrelated risk factors (preoperative anaemia, perioperative RBC transfusions, and the need for reexploration) were strongly associated with the development of AKI. Very recently, Parolari et al. performed a large single-centre study in 3669 patients who underwent on-pump cardiac surgery, using the modified AKIN (SCr only) to define AKI. This demonstrated that as well as conventional preoperative risk factors for AKI such as increasing age, preoperative SCr, and diabetes, drug administration (especially inotropes, vasoconstrictors, diuretics), RBC transfusion, and perfusion or cross-clamp times were significantly associated with AKI. However, an obvious limitation of all these retrospective studies is the potential for confounding effects, particularly when the trigger for intervention is not clearly defined. Thus, RBC transfusion during cardiac surgery may contribute to AKI but is itself often consequent to significant blood loss, the cause of which may also contribute to the development of AKI. Likewise, furosemide may contribute directly to AKI, but again, it may be that the administration of the diuretic was initiated by a response to oliguria heralding AKI. Therefore, despite the fact that this study implies that transfusion and diuretic administration are independent risk factors for the development of CS-AKI we are left wondering whether this is the chicken or the egg. However, this study does raise some interesting points. Transfusion of RBCs may cause AKI through interaction