Association of hyperchloremia with mortality and acute kidney injury in critically ill children: a systematic review and meta-analysis

Abstract Background Blood chloride disturbances are common in critically ill children. However, the prognostic significance of hyperchloremia remains uncertain because serum chloride abnormalities may be confounded by the severity of the underlying illness. This systematic review and meta-analysis aimed to describe the reported prevalence of hyperchloremia and evaluate its association with short-term mortality and acute kidney injury (AKI) in critically ill children admitted to the pediatric intensive care unit (PICU). Methods We systematically searched PubMed, Embase, and Web of Science from database inception to May 31, 2026. Eligible studies enrolled critically ill patients aged 0–18 years in PICUs and reported adjusted associations of hyperchloremia with short-term mortality or AKI. Hyperchloremia was defined using study-specific thresholds (> 109, ≥ 110, or > 110 mmol/L), and chloride exposures were categorized as admission hyperchloremia, peak chloride during the PICU stay, or ICU-period chloride measures. Short-term mortality comprised PICU, hospital, or 28-day mortality, whereas AKI was ascertained using study-reported KDIGO criteria or ICD-9/10 administrative codes. Only adjusted estimates were included in quantitative syntheses. Results Seven reports representing six independent observational cohorts and 22,996 unique participants were included. The reported prevalence of hyperchloremia ranged from 6.8% to 51.4%, depending on the study population and chloride-exposure definition. Admission- and peak-chloride short-term mortality estimates were synthesized narratively because the contributing studies were not sufficiently comparable for quantitative pooling. An exploratory synthesis of two estimates evaluating mean chloride during the first seven PICU days showed higher odds of short-term mortality (pooled aOR 2.34, 95% CI 1.57–3.48; I²=0%); the certainty of evidence was low. For AKI, single-study estimates for initial and maximum chloride were reported narratively. An exploratory synthesis of three ICU-period chloride estimates showed higher odds of AKI (pooled aOR 2.10, 95% CI 1.58–2.79; I²=0%); the certainty of evidence was very low. Very-low-certainty evidence for RRT was inconsistent, and very-low-certainty evidence from one study did not show a clear association with duration of mechanical ventilation. Conclusions Limited observational evidence from exploratory syntheses suggests that hyperchloremia defined using mean chloride during the first seven PICU days may be associated with higher odds of short-term mortality, while ICU-period chloride measures may be associated with higher odds of AKI in critically ill children. These findings do not establish causality and should be interpreted cautiously because few cohorts contributed, chloride-exposure and outcome definitions differed, and residual confounding and exposure–outcome timing remain concerns. Very-low-certainty evidence for RRT and duration of mechanical ventilation remained inconclusive. Prospective studies with standardized serial chloride assessment are needed to clarify these associations, while adequately designed randomized trials are required to evaluate the clinical effects of fluid strategies. Systematic review registration PROSPERO CRD420261400801.