The causal link between hyperchloremia and acute kidney injury is yet to be conclusively established: we are not sure

Excerpt

We read with interest the recent article by Williams et al. comparing Plasma-Lyte-A with 0.9% saline in children with diabetic ketoacidosis (DKA) [1]. They conclude that both fluids were similar in regard to time to resolution of DKA, need for renal replacement therapy (RRT), mortality, and lengths of pediatric intensive care unit (PICU) and hospital stay [1]. In addition, the incidence of new or progressive acute kidney injury (AKI) and resolution of AKI were similar in both groups. They conclude that the cause for hyperchloremia seems more of a normal physiological response to loss of bicarbonate over chloride with improved renal perfusion than due to fluid type or volume. We would like to make some comments. The chloride elevation in this study was very modest in both groups—only 4 mmol/L for the Plasma-Lyte group and 6 mmol/L for the normal saline group [1]. If we look at the study of Baalaaji et al. [2], where all the patients were resuscitated with saline, the chloride in the non-AKI group was 106.6 mmol/L versus 118.6 mmol/L in the AKI group, a difference in chloride of 12 mmol/L [2]. In that study, twenty-eight (35%) children were diagnosed with AKI: twenty (71.4%) recovered with hydration alone while 8 (28.6%) required RRT [2]. None of the admission variables could predict AKI; however, on multivariable analysis, elevated chloride levels at 24 h had an independent association with AKI progression [adjusted OR 1.14 (95% CI 1.04–1.27), P = 0.007]. Serum chloride > 112 mmol/L at 24 h had a sensitivity, specificity, and area under ROC curve of 73.3%, 82.4%, and 0.835, respectively, for development of AKI (P < 0.001) [2]. Although children with “AKI progression” had higher PRISM III and admission chloride levels, only the 24-h serum chloride was independently associated with “AKI progression.” Independent association of the 24-h serum chloride rather than admission value leads one to believe that hyperchloremia could have been an iatrogenic element caused by the type of intravenous fluids received [2]. Hyperchloremia has been hypothesized to cause renal hypoperfusion and AKI by virtue of its renal vascular smooth muscle constrictor effect [3, 4]. A causal link between hyperchloremia and AKI has yet to be proven or disproven. Further randomized controlled studies are needed to elucidate the relationship between fluids and AKI. …