RenalHyperchloraemia is associated with acute kidney injury and mortality in the critically ill: A retrospective observational study in a multidisciplinary intensive care unit
Introduction
Disorders of chloride are relatively under-researched in comparison to disorders of sodium [1]. Traditionally chloride was viewed as the passive anionic companion of sodium. While the association between hyperchloraemia and metabolic acidosis is well established, the clinical consequences of hyperchloraemia are unclear [[2], [3], [4]].
Wilcox demonstrated that hyperchloraemia results in renal vasoconstriction in an animal model, with Chowdhury recently reporting similar findings with the use of 0.9% saline versus balanced salt solutions in human subjects [[5], [6], [7]].
Studies examining AKI and hyperchloraemia have shown conflicting results. While some have shown an association in postoperative, septic and intensive care unit (ICU) patients [[8], [9], [10], [11], [12]], others have shown no such association [13]. Of these studies only one explored the association between chloride kinetics (the change in chloride over time) and AKI and found an increased incidence of AKI in patients who had shown an increase in chloride [12].
A relationship between increased mortality and hyperchloraemia has also been reported [8,[14], [15], [16], [17]]. Other studies have not shown this association [10,12], and there was no significant association between the use of a chloride-liberal or a chloride-restrictive fluid strategy and mortality [[18], [19], [20], [21]].
Despite these previous studies, there are numerous limitations in the current knowledge base. Of the studies discussed above, only 10 specifically evaluated the association between serum chloride and the outcomes of interest, of these, 6 reported AKI as an outcome and 7 reported mortality as an outcome. Only one study each evaluated the association between chloride kinetics and AKI and mortality [12,16]. Six studies evaluated exclusively ICU patients, with only 3 including a proportion (27.8%–64.0%) of non-surgical patients [9,10,15]. Only 3 studies were in low- or middle-income countries, with no studies in Africa. Based on these limitations we aimed to examine the association between hyperchloraemia in the first 48 h of ICU and AKI and mortality in a heterogenous critically ill population in South Africa. We also sought to explore the association between chloride kinetics and the abovementioned outcomes and the association between sodium and acid-base parameters and AKI and mortality.
Section snippets
Materials and methods
This was a retrospective observational study of patients admitted to King Edward VIII Hospital Intensive Care Unit from to 26 September 2015 to 09 May 2016. The study ICU is a multidisciplinary, closed, intensivist-run ICU in a tertiary academic hospital that serves the province of KwaZulu-Natal in South Africa.
AKI was defined according to Kidney Disease Improving Global Outcomes (KDIGO) criteria, using the serum creatinine and renal replacement therapy criteria [22]. Urine output criteria were
Results
The derivation of the study population is shown in Fig. 1 and baseline demographic and outcome data is presented in Table 1.
Of the 150 patients that developed AKI, 31.3% had stage 1 AKI, 31.3% stage 2 AKI and 37.3% stage 3 AKI. Ninety-eight percent had developed AKI by 48 h of ICU admission.
Admission serum chloride was available for all 250 patients, with 48-h chloride available for 163 patients. Hyperchloraemia was noted in 42.0% of patients on ICU admission, and 36.8% at 48 h. Overall 57.2%
Discussion
This study presents data for a cohort of patients that has not previously been represented in the international literature. The cohort was remarkably young, with a median age of 35 years, compared to the 6th and 7th decades for previous studies [9,10,14,15]. The high incidence of sepsis (45.2%) reflects the burden of infectious disease in the study country. The high incidence of shock on admission (53.6%), AKI (60.0%), and ICU mortality rate (39.2%) reflect the increased severity of illness of
Limitations
The retrospective observational nature of the study is a limitation; however, the study did not rely simply on a retrospective analysis of an electronic database but used the patient's original medical record to source individual patient data, optimising the quality of the data collected. Patient weights were not known and thus urine output criteria were not used to diagnose AKI. It is anticipated that the inclusion of urine output criteria would have increased the incidence of AKI, but it is
Conclusions
Hyperchloraemia and increases in serum chloride are associated with increased incidences of both AKI and ICU mortality in a heterogenous ICU population, with hyperchloraemia at 48 h after ICU admission being an independent predictor of both AKI within the first 7 days of ICU admission and ICU mortality. While the findings warrant concern, this study suggests there is still equipoise as to whether the findings represent association, causation or are an epiphenomenon (possibly related to altered
Ethics approval
Approval for the study was obtained from the University of KwaZulu-Natal Biomedical Research Ethics Committee (BE 492/15), King Edward VIII hospital, and the Health Research Committee of the KwaZulu-Natal Department of Health.
Consent for publication
Not applicable.
Availability of data and material
The datasets used during the current study are available from the corresponding author on reasonable request and subject to approval of the above ethics committees.
Competing interests
The authors declare that they have no competing interests.
Funding
This research did not receive any
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