Sodium bicarbonate has been used for several years for its presumed nephroprotective effects in several settings. In particular, its role in cardiac surgery-associated acute kidney injury (CSA-AKI) has been explored. CSA-AKI is a particular type of cardio-renal syndrome for which no clear understanding of pathogenesis exists and no proven effective prophylaxis or treatment has as yet been established [1]. Previous studies have reported injury to red cells and release of free haemoglobin during cardiopulmonary bypass (CPB) [2]. Besides complete red blood cell fragmentation (induced by CPB, valvular prosthesis, transfusion reactions or genetic defects predisposing to reduced erythrocyte membrane stability), there can also be sublethal red cell damage, resulting in altered rheological properties. Increased levels of free red blood cell constituents, together with an exhaustion of their scavengers, transferrin and haptoglobin, result in a variety of serious clinical consequences, such as increased systemic vascular resistance, altered coagulation prof ile, platelet dysfunction, renal tubular damage and increased mortality. Such injury raises concerns that CSA-AKI may be a form of renal sideropathy and that free or inappropriately liganded iron-related toxicity may play a role [3]. Free iron has the potential to catalyse the formation of super-oxide radical and hydrogen peroxide yielding hydroxyl radical. It is known that an acid environment typical of tubular urine enhances the formation of reactive hydroxyl radicals. Finally, tubular obstruction may allow greater time for endocytotic uptake of free haemoglobin into proximal tubular cells, which is associated with proximal tubular cell necrosis. Oxidative stress has been shown to play a key role in the development of toxic and ischaemic AKI. Interestingly, urinary alkalinization with sodium bicarbonate might protect from the pathophysiological mechanisms causing CSA-AKI. A recent double-blind randomized controlled trial showed that bicarbonate might attenuate CSA-AKI, potentially directly affecting iron-related toxicity, as indicated by a smaller increase in urinary biomarker neutrophil gelatinaseassociated lipocalin (NGAL) [4]. At neutral or alkaline pH, free ferric ions precipitate as insoluble ferric hydroxide, which is excreted as inert complex in the urine. More alkaline urine reduces the generation of injurious hydroxyl radicals and lipid peroxidation. Bicarbonate directly scavenges hydroxyl ions and, as a not well-adsorbable anion compared with chloride, causes more rapid volume excretion and thereby reduces the contact time between injurious radicals and renal tubules. Peak plasma creatinine increases were typical by the third post-operative day regardless of the study group. Furthermore, exposure to sodium bicarbonateattenuated renal oxidative stress as reflected by lower urinary NGAL levels and urinary NGAL/creatinine ratios. As expected, exposure to sodium bicarbonate infusion was associated with a higher plasma pH, higher plasma bicarbonate and urinary alkalinization. Fewer patients in the sodium bicarbonate group (16 of 50) developed a post-operative increase in serum creatinine compared with control (26 of 50) (P = 0.043). The increase in plasma creatinine, plasma urea, urinary NGAL, and urinary NGAL/urinary creatinine ratio was less in patients receiving sodium bicarbonate. As the authors acknowledge, bicarbonate apparently preventedonly mild renal dysfunction which may have limited effects on clinical outcome. Furthermore, the potential clinical risks of systemic alkalinization, e.g. oxyhaemoglobin dissociation curve shifts resulting in higher oxygen–haemoglobin affinity with possible relative tissue hypoxaemia, have not been fully evaluated in this pilot trial. The effects of bicarbonate on higher risk cardiac surgery patients remain to be evaluated. These results suggest finally a novel utility of urinary NGAL measurements not as diagnostic biomarker but as monitor of the efficacy of therapy for AKI. Sodium bicarbonate has also been used for nephroprotection in contrast-induced acute kidney injury (CI-AKI). The benefit of CI-AKI prophylaxis has mainly been shown for patients with reduced glomerular filtration rate (GFR) (<50 mL/min/1.73 m), heart failure or diabetes, and/or patients with high risk scores (Thakar score [5] or Mehran score [6]). In this light, intensive care unit (ICU) patients undergoing angiography should always be considered as high-risk patients. The International Consensus Conference in Intensive Care Medicine recently considered the
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Jan 1, 2015
Angeletti S + 1
