The results obtained in this study are consistent with previous that have reported AKI incidence in pediatric patients with DKA ≈ 50%. For example, in a recent study, the incidence of AKI occurred in 43% of DKA patients, the majority (94.7%) presenting concurrently with DKA diagnosis and only 3.8% showed normal creatinine levels at the time of DKA diagnosis [19]. In a retrospective study from 2008 to 2017 performed in a pediatric hospital in Taiwan, a frequency of AKI in patients with DKA was found to be 56.5% [10]. In another study conducted in Mexico City in 2017, an AKI frequency of 54% was reported in this population [12].
Hyperchloremia as a finding of this study is also consisted with other authors, as reported by Toledo et al, with a frequency of 55% in children with DKA [20].
Hyperchloremic acidosis is a problem that can occur upon admission to the emergency department or during rehydration therapy in these patients [21, 22].
In the present study, the cut-off point for hyperchloremia with risk of AKI was 110 mg/dL, similar with that reported by Khan et al., who with this same level of hyperchloremia reported an OR of 1.7 (95% CI 1.4–2.1) for the development of AKI in children in the intensive care unit [23].
A serum chloride value ≥ 110 mg/dL on admission has also been associated with mortality risk in critically ill pediatric patients [24]. Even more, in our study, it was observed that the increase in serum chloride levels shows positive correlations with both the AKI level and creatinine levels.
Studies in animal models suggest that hyperchloremia is associated with alterations in local hemo-rheology, immune system response, coagulation disorders and pulmonary dysfunction, all of them, factors that could contribute to increasing AKI [25, 26].
Also, the complex renal physiology related to the role of chloride in the regulation of renal blood flow, glomerular filtration rate, tubulo-glomerular feedback, and tubular injury has been reported, since the kidney is an important regulator of chloride homeostasis, and its tubular reabsorption is essential to maintain the volume of extracellular fluid. It is even pointed out that arterial chloride levels could have a greater effect than venous chloride on factors such as renal blood flow and therefore on the glomerular filtration rate [27, 28].
A current research topic is the type of rehydration regimen that patients with hyperchloremic acidosis should receive. Systematic reviews have been carried out on the effectiveness of rehydration and the risk of secondary hyperchloremia and AKI using different types of solutions and rehydration schemes in critically ill children, but they are not yet conclusive [29].
Regarding the association of HbA1c with the development of AKI, it has been found that HbA1c levels above 6.9% are associated with the development of AKI in adult patients with type 2 diabetes mellitus (DM) and confirmed DKA, as reported in 2020 in a big sample size of patients from the United States and Sweden [30].
In another prospective study, it was observed that 16% of adult patients with type 2 DM and acute myocardial infarction had AKI; and both HbA1c levels and serum glucose levels at admission had a high level of prediction for this complication [31]; which agrees with the results of this study in which a strong association [OR 11 (95% CI 2–60) (p = 0.006)] was observed between HbA1c levels (≥ 13%) and the development of AKI in pediatric patients with DKA.
The main limitation of our study is its retrospective design and small sample size, but it is strengthened by the review of records with detailed information on biochemical measurements at admission and during clinical evolution. The results of this research can serve as a basis for future intervention studies that analyze the effects of different rehydration schemes to prevent hyperchloremia, AKI and at long term, the risk of developing chronic kidney disease.