Sepsis is a condition characterized by a malfunctioning immune reaction to infection, the dysregulation between the pro—coagulant and anticoagulant systems within the body is acknowledged as one of the pathogenic reasons underlying sepsis, resulting in potentially fatal organ dysfunction (1, 2). And the global health equity gap is particularly detrimental to children, increasing their susceptibility to infectious diseases. Studies have pointed out that each year, 50 million people worldwide are infected with sepsis, of whom half are newborns and children under the age of 19 (3). Pediatric severe sepsis (PSS) is a life-threatening condition and one of the leading causes of mortality in children worldwide. The prevalence of severe sepsis has been reported to be increasing in recent years (4), due to rising complications (5, 6), more frequent multidrug—resistant and opportunistic infections (7, 8), and improved surveillance and diagnosis (9, 10). Among the series of pathological changes caused by severe sepsis, the kidneys are among the most frequently affected organs. However, the diagnosis of AKI relies on changes in serum creatinine and urine output—indicators that are often lagging and non-specific, making early recognition and timely intervention particularly challenging (11, 12). In addition to insufficient renal perfusion, microvascular dysfunction, inflammation, and the response of cells to inflammatory injury can all contribute to sepsis-related acute kidney injury, which may progress to chronic kidney disease, imposing a substantial long-term health burden—a sequela often more significant than that of resolved dysfunction in other organ systems (13, 14). Children suffering from this severe illness generally face a heightened risk of sepsis-associated acute kidney injury (SA—AKI) (15, 16), which further elevates morbidity and mortality (17). Nevertheless, data on AKI's impact on hospital outcomes in PSS inpatients and its associated factors remain scarce.

The primary objectives of our study were as follows: (1) to evaluate the temporal trends in incidence and outcomes of PSS patients with concurrent AKI, as well as the associated factors; and (2) to determine the impact of AKI on sepsis patients during the same time period.

Epidemiological characteristics of pediatric severe sepsis vary across studies, likely due to differences in populations, observation periods, and diagnostic criteria. We analyzed 225,902 associated hospitalizations of patients with sepsis aged 0–18 years between 2010 and 2019. Key findings included: (1) The incidence of AKI in PSS patients increased nearly three times (from 2.7% to 8.0%), while in-hospital mortality decreased by nearly half (from 32.4% to 17.9%); (2) PSS—AKI patients had significantly longer hospital stays (17 vs. 7 days) and higher hospitalization costs ($235,912 vs. $43,077) than non—AKI patients, though both metrics showed a downward trend over time; (3) AKI risk was strongly associated with specific comorbidities (e.g., fluid-electrolyte disturbances, coagulation disorders), infection sites (e.g., gastrointestinal infections), and pathogens (e.g., Escherichia coli, Staphylococcus aureus); (4) We observed that among patients with PSS—AKI, the most common age groups were infants <1 year (39.69%) and 11–18 years (31.88%), and the incidence rate was higher in male patients (53.64% vs. 46.36%); (5) Those with multiple comorbidities had the highest in-hospital mortality.

Our study highlights a rising incidence of AKI in PSS inpatients over a decade, alongside declining mortality—a trend consistent with other studies, including in adults (4, 18, 19). This trend may reflect increased global attention to pediatric sepsis, promoting earlier and more aggressive management. Advances in diagnosis, monitoring, and treatment may also have mitigated disease severity. Thus, while overall AKI incidence increased, mortality declined. We also found that hospital stays and costs were substantially higher for PSS—AKI patients, though both decreased over time. Optimizing management to prevent AKI progression may help reduce length of stay and costs.

In the European Children's Infectious Disease Study (EUCLIDS), half of the children were confirmed to have invasive bacterial infections, and one-third of the survivors were discharged with disabilities (20). Numerous studies have shown that early identification of pathogens and timely administration of antibiotics are crucial and have beneficial effects on prognosis (21–23). In our study, Staphylococcus aureus, Escherichia coli and Streptococcus were prevalent; however, it should be noted that these pathogen-specific findings are based on clinical diagnosis codes rather than laboratory-confirmed microbiology. While this may not fully capture the true etiologies, the patterns observed can still offer valuable references for clinical prevention and intervention. Among all infection sites, gastrointestinal infections showed the closest association with PSS—AKI. It has been reported that factors such as a younger age, blood—related or immunological comorbidities, malignancies, and abdominal infections are linked to severe AKI (24), and in our study we noted an increased proportion of AKI in patients with water and electrolyte disorders, coagulation disorders, other neurological disorders, hypertension, chronic lung disease, valvular disease, paralysis, congestive heart failure. Among them, fluid and electrolyte imbalance, which is a recognized risk factor, usually reflects the cumulative effects of capillary leakage, active resuscitation and potential disease severity in sepsis. Coagulation dysfunction is also prominent in our model. It is a known component of organ dysfunction caused by sepsis and can exacerbate renal microvascular damage (25, 26). Reducing these risk factors and implementing early interventions may slow PSS—AKI progression.

In summary, integrating these data-driven strategies into clinical practice is crucial. This entails enhanced monitoring of high-risk patients—clinicians should maintain a heightened suspicion for AKI in neonates, male patients, and those with specific comorbidities such as fluid-electrolyte imbalances, coagulation disorders, or hypertension. Concurrently, focused attention on high-risk pathogens and infection sites necessitates proactive preventive measures and the prompt administration of appropriate antibiotic therapy. Implementing such a targeted approach may help mitigate the progression of PSS—AKI, thereby potentially alleviating its substantial healthcare burden and reducing associated mortality.

We utilized a large, nationally representative database to accurately capture real-world trends in morbidity and mortality. However, this study has several potential limitations. First, the retrospective, administrative nature of the data introduces the possibility of recording bias due to inconsistent identification and coding practices, which may lead to an underestimation of AKI incidence. Moreover, the database contains only in-hospital information, lacking post-discharge follow-up and out-of-hospital mortality data, thus providing an incomplete clinical picture. Second, we lacked data on specific exposures such as nephrotoxic medications and radiocontrast agents, which are known risk factors for AKI. Third, important treatment variables that influence sepsis outcome—including mechanical ventilation and renal replacement therapy—were not available for adjustment in our multivariate models, potentially confounding the observed association between AKI and mortality. Fourth, we could not fully address the interplay between comorbidities and pre-existing chronic kidney disease (CKD); excluding patients with pre-existing CKD or a history of AKI can mitigate such bias and enhance the validity of the findings. Fifth, although immunocompromised children were included in the cohort, we did not perform a dedicated subgroup analysis for this population, so our results may not fully reflect their distinct risk profile and outcomes. An additional limitation is the granularity of age data within this group; the use of a single “<1 year” category, necessitated by the database structure, precludes a more nuanced analysis distinguishing neonates from older infants. What's more, the risk factors, prevalence, clinical and microbiological etiology of newborns and infants (<1 year old) are significantly different from those of older children and adolescents, and their pathophysiological mechanisms are also quite distinct (27, 28), but we do not exclude them.

Between 2010 and 2019, the incidence of PSS with or without AKI increased among hospitalized children. AKI was associated with higher mortality, morbidity, longer hospital stays, and greater resource use, increasing public health burden. However, with the deepening of pediatric sepsis research and the improvement of medical level, the overall mortality rate of PSS has decreased, especially the mortality rate of PSS patients with AKI has shown a significant decreasing trend. Therefore further research and technological innovation are necessary to improve early diagnosis of AKI, identification of risk factors, and timely implementation of preventive treatment, This is of crucial significance for improving children's health and reducing the risk of adverse consequences caused by infections and related diseases.