Dyschloremia Is a Risk Factor for the Development of Acute Kidney Injury in Critically Ill Patients

RESEARCH ARTICLE Dyschloremia Is a Risk Factor for the Development of Acute Kidney Injury in Critically Ill Patients Min Shao1,2,3, Guangxi Li2,4, Kumar Sarvottam1,2, Shengyu Wang2,5, Charat Thongprayoon2, Yue Dong2, Ognjen Gajic2,6, Kianoush Kashani1,2,6* 1 Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN, United States of America, 2 Multidisciplinary Epidemiology and Translational Research in Intensive Care (METRIC) Research Group, Mayo Clinic, Rochester, MN, United States of America, 3 Department of Critical Care Medicine, Anhui Provincial hospital Affiliated to Anhui Medical University, Hefei, Anhui, China, 4 Department of Pulmonary Medicine, Guang’Anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China, 5 Department of Pulmonary Medicine, The First Affiliated Hospital of Xi’an Medical University, Shaanxi, China, 6 Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic, Rochester, MN, United States of America a11111 * Abstract Introduction OPEN ACCESS Citation: Shao M, Li G, Sarvottam K, Wang S, Thongprayoon C, Dong Y, et al. (2016) Dyschloremia Is a Risk Factor for the Development of Acute Kidney Injury in Critically Ill Patients. PLoS ONE 11(8): e0160322. doi:10.1371/journal.pone.0160322 Editor: Giuseppe Remuzzi, Mario Negri Institute for Pharmacological Research and Azienda Ospedaliera Ospedali Riuniti di Bergamo, ITALY Received: January 19, 2016 Accepted: July 18, 2016 Dyschloremia is common in critically ill patients, although its impact has not been well studied. We investigated the epidemiology of dyschloremia and its associations with the incidence of acute kidney injury and other intensive care unit outcomes. Material and Methods This is a single-center, retrospective cohort study at Mayo Clinic Hospital—Rochester. All adult patients admitted to intensive care units from January 1st, 2006, through December 30th, 2012 were included. Patients with known acute kidney injury and chronic kidney disease stage 5 before intensive care unit admission were excluded. We evaluated the association of dyschloremia with ICU outcomes, after adjustments for the effect of age, gender, Charlson comorbidity index and severity of illness score. Published: August 4, 2016 Copyright: © 2016 Shao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: The authors received no specific funding for this work. Competing Interests: The authors have declared that no competing interests exist. Results A total of 6,025 patients were enrolled in the final analysis following the implementation of eligibility criteria. From the cohort, 1,970 patients (33%) developed acute kidney injury. Of the total patients enrolled, 4,174 had a baseline serum chloride. In this group, 1,530 (37%) had hypochloremia, and 257 (6%) were hyperchloremic. The incidence of acute kidney injury was higher in hypochloremic and hyperchloremic patients compared to those with a normal serum chloride level (43% vs.30% and 34% vs. 30%, respectively; P < .001). Baseline serum chloride was lower in the acute kidney injury group vs. the non-acute kidney injury group [100 mmol/L (96–104) vs. 102 mmol/L (98–105), P < .0001]. In a multivariable logistic regression model, baseline serum chloride of 94 mmol/L found to be independently associated with the risk of acute kidney injury (OR 1.7, 95% CI 1.1–2.6; P = .01). PLOS ONE | DOI:10.1371/journal.pone.0160322 August 4, 2016 1 / 13 Chloride Abnormalities in Intensive Care Unit Discussion Dyschloremia is common in critically ill patients, and severe hypochloremia is independently associated with an increased risk of development of acute kidney injury. Introduction Acute kidney injury (AKI) is a grave and common complication of critical illness. Despite significant progress in the care of critically ill patients, the mortality rate in AKI patients remains high. Recent studies indicate AKI incidence among all hospital admissions is 3–10%, in-the general hospital wards, and intensive care unit (ICU) mortality rates are 20% and 50%, respectively [1, 2]. Annually, about two million patients die of AKI [3] and those who survive AKI are apt to develop chronic kidney disease (CKD) [4, 5]. Appropriate AKI risk stratification among ICU patients is helpful to prevent AKI and its progression and/or design trials to test the utilization of therapeutic options. Knowing each individual risk profile is critical in the process of preventive and/or therapeutic interventions. Sepsis, trauma, shock, nephrotoxic agents, and contrast media exposure are known risk factors for AKI. Despite growing knowledge in the field, there are several other risk factors that have not been well described or identified. Chloride is one of most affluent anions in the plasma and interstitial fluid. It accounts for approximately one-third of plasma tonicity and participates in acid-base balance [6]. Serum sodium serves as the primary extracellular cation and serum chloride as the primary extracellular anion [7]. Several studies have examined the epidemiology of sodium disturbances and their possible impact on adverse outcomes in critically ill patients [8–10]. The incidence of dysnatremia in ICU patients varies between 25% and 45%. Even mild hyponatremia and hypernatremia is associated with significantly higher mortality and longer duration of hospitalization [10]. Although chloride abnormalities, particularly hypochloremia, are very common in critical care settings, they have not received appropriate attention. In comparison with the volume of literature in dysnatremia, the number of studies reporting the incidence and impact of dyschloremia on patient outcomes is very limited. Hypochloremia is associated with metabolic alkalosis. Infusing chloride-rich solutions like normal saline may be the first choice for the resuscitation of patients with alkalemia and hypochloremia. On the other hand, a growing volume of evidence indicates the use of chloride-rich intravascular fluids are associated with high occurrence of AKI, metabolic acidosis, and hyperkalemia. This association is more evident when these solutions are administrated in large quantities [11–14]. Despite significant progress in the field, the current body of knowledge on the incidence and impact of baseline plasma chloride on clinical outcomes, and on AKI specifically, are very preliminary. This study aimed to explore the association of baseline serum chloride and the development of AKI in ICU patients. We hypothesized that baseline serum chloride is closely associated with AKI development during ICU stay. Materials and Methods Patients and study design This stu (...truncated)