Hyperchloremia and acute kidney injury: a spurious association or a worrisome reality?

Chloride is the most common anion in the extracellular fluid, and plays a pivotal role in the maintenance of plasma tonicity [1]. Based on this premise, the use of 0.9% sodium chloride (NaCl) solution, which is usually referred to as “normal saline” (NS), has been used since the early nineteenth century as a resuscitation fluid [2]. However, the 154 mmol/L chloride concentration in the 0.9% NaCl solution is far from being “normal” with respect to the usual 95–105 mmol/L chloride concentration found in plasma. Thus hyperchloremia, defined as plasma chloride concentration above 110 mmol/L, can be produced by infusion of large volumes of NS [3], and is also observed in patients with non-anion gap metabolic acidosis caused by direct or indirect loss of plasma bicarbonate through the intestine or the kidney [4]. In the last years, growing concern has arisen towards the use of NS as a resuscitation fluid in critically ill patients based on experimental and clinical evidence pointing to a nephrotoxic effect of large chloride amounts