Treatment for critically ill children with cardiac diseases primarily involves medications, surgical interventions, and lifestyle modifications aimed at reducing symptoms and improving quality of life. However, In these patients, AKI often occurs and is significantly linked to an elevated risk of perioperative mortality (1). Reported AKI incidence after cardiac procedures ranges from 15% to 64% (2, 3). Moreover, AKI elevates perioperative mortality by 3 to 8 times (4, 5). AKI is also linked to long-term renal dysfunction, cardiac complications, and a reduced overall quality of life (6). These observations underscore the need for early identification and targeted interventions to improve outcomes.

Insulin resistance (IR) refers to impaired insulin sensitivity, resulting in increased circulating insulin levels and disrupting normal metabolic processes (7, 8). IR may impair kidney function via several pathways, including endothelial dysfunction, heightened inflammation, and tubulointerstitial fibrosis (9, 10). The TyG index, which reflects IR, is calculated by fasting triglycerides (TG) and fasting plasma glucose (FPG) (11, 12), has shown significant value in the context of AKI in recent years (13, 14). A substantial link between an increased TyG index and AKI has been observed in adult studies. Among individuals undergoing Coronary revascularization, the biomarker for contrast-induced AKI could be the TyG index. Across adult cohorts, including those undergoing coronary revascularization and those with traumatic brain injury, hypertension, or diabetes, the TyG index has been studied as an early indicator of AKI. (15–19). Across these adult cohorts, the TyG index is a practical tool for AKI risk assessment.

In pediatric populations, the TyG index correlates with insulin resistance and cardiometabolic risk (20, 21), underscoring its biological relevance in children. Because the TyG index integrates FPG and TG, it reflects dysglycemic and insulin-resistant states linked to renal vulnerability. Mechanistically, both hypoglycemia and hyperglycemia may precipitate AKI via sympathetic activation with hemodynamic instability, oxidative stress, endothelial dysfunction, and direct tubular injury (22, 23). Consistent with this biology, a U-shaped association between TyG index and short-term mortality has been reported in critically ill children (18). Accordingly, we hypothesized that the association between the TyG index and AKI in critically ill children with cardiac diseases may likewise be U-shaped.

To date, pediatric studies have used the TyG index primarily as a surrogate for insulin resistance and broader cardiometabolic risk, rather than as a marker of renal injury. Against this background, we examined the association between TyG and AKI in critically ill children with cardiac diseases. Given the high incidence of AKI in this population and its adverse long-term consequences, we further evaluated whether TyG could serve as an early, readily available biomarker for AKI risk to inform timely monitoring and management.

To our knowledge, this large retrospective study is the first to examine the association between the TyG index and AKI in children with cardiac disease. After adjustment for confounders, we observed a nonlinear, U-shaped association with both AKI and severe AKI. Spline analyses identified inflection points at 8.602 and 8.757, respectively. These findings highlight dual clinical implications: the TyG index may serve as an early, readily available marker to support AKI risk stratification in practice. Additionally, for dynamic bedside monitoring, given the small difference between the two cut-points, we prefer to interpret these values as evidence for a shared low-risk band (8.60–8.76) rather than as rigid single-number cut-offs. This difference is likely driven by several considerations. Clinically, severe AKI typically requires a stronger metabolic and hemodynamic insult to become manifest; therefore, at higher TyG levels the point at which risk begins to rise is expected to be slightly right-shifted relative to AKI. In our cohort, event frequency also differed markedly (AKI 15.6% vs severe AKI 3.3%). With fewer events, the spline-based change-point is more susceptible to sampling variability and tends to gravitate toward regions with denser observations, yielding a modestly higher threshold.

Because the TyG index jointly reflects dysglycemia and triglyceride-related lipotoxic stress and serves as a validated surrogate of insulin resistance (33), it may reflect biology relevant to AKI more completely than fasting glucose or triglycerides alone. Clinically, this translates into pragmatic benefits at the bedside: the TyG index is derived from FPG and TG, can be auto-calculated for real-time risk flagging, and requires no additional assays, phlebotomy, or turnaround time. The observed U-shaped pattern with a narrow low-risk band further supports avoiding both hypoglycemia and marked hyperglycemia and using alerts based on TyG to prompt early monitoring and metabolic care. In contrast, injury or functional biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C primarily reflect tubular injury or filtration impairment and therefore require appropriate post-injury timing; by comparison, the TyG index functions as an antecedent risk marker obtainable before overt damage (34, 35). Accordingly, the TyG index should be viewed as complementary, not a replacement, to organ-specific injury markers.

Over the past few years, the TyG index has attracted growing interest as a potential indicator of AKI risk. However, research on this association remains limited, with most studies focusing on adult populations. Multiple studies report a positive association between TyG and AKI across diverse conditions. Among patients undergoing coronary revascularization, The highest TyG quartile (Q4) showed an 89% increased risk of AKI relative to the lowest quartile (Q1) (HR 1.89, 95% CI 1.12–3.17, P = 0.017) (33). Similarly, in patients with heart failure, A one-unit boost in the TyG index correlated with a 58% higher risk of AKI (HR 1.58, 95% CI 1.22–2.04, P = 0.0006) (36). In patients with hypertension, A TyG index ≥4.803 substantially heightened AKI risk (P < 0.001), the top quartile had a 66% incidence, significantly exceeding than the 47% seen in the lowest group (P < 0.001) (15). In sepsis, A rise in the TyG index corresponded to a greater risk of developing AKI (HR 1.073, 95% CI 1.005–1.147, P = 0.036) (37). Collectively, higher TyG is associated with greater AKI risk across adult cohorts; however, its relationship with AKI in children with cardiac disease has not been defined. The present study helps to fill this gap. and provides foundational data for future research.

In contrast to previous studies, we observed a U-shaped association between the TyG index and AKI in children with cardiac disease, rather than the positive linear association described previously. A primary explanation is endpoint definition: compared with adult Kidney Disease: Improving Global Outcomes (KDIGO) criteria (38), the pediatric pROCK uses lower diagnostic thresholds and is easier to trigger (27), yielding milder AKI; such definition differences alter case ascertainment and the severity mix, potentially changing the shape of the association. A second contributor is exposure distribution. Our cohort’s median TyG was 8.61, whereas adult cohorts typically centered higher (about 9.15), so prior analyses likely operated in a range where risk appears more monotonic. Consistent with a nonlinear framework, three studies of atrial fibrillation, all-cause mortality, and incident diabetes reported lowest risk at intermediate TyG, with higher risks at both tails (18, 39, 40); their TyG ranges were similar to or lower than ours. Taken together, differences in AKI definitions and TyG distributions across settings likely underlie the discrepant association shapes.

We propose several mechanisms that may underlie the U-shaped relationship between the TyG index and AKI. The TyG index is a composite measure derived from TG and FPG, has been proven to be a reliable indicator for evaluating IR (41). When the TyG index exceeds 8.602, higher TyG may be associated with greater AKI risk through IR-related pathways, including: (1) induction of glomerular hyperfiltration, where abnormal hemodynamic changes may aggravate tubular dysfunction (42); (2) activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS), which, when excessively activated, not only induces vasoconstriction and reduces renal blood flow but also increases renal pressure, further impairing renal perfusion and function (43, 44); (3) oxidative stress triggered by IR, resulting in excessive production of reactive oxygen species (ROS), which damage renal cells, particularly mitochondria, resulting in cellular dysfunction (45, 46); and (4) IR-induced inflammatory responses that promote the release of inflammatory cells and cytokines, creating a chronic inflammatory environment that accelerates renal deterioration (47). When TyG < 8.602, the inverse association may be associated with a hypoglycemic metabolic state. The mathematical composition of the TyG index suggests that low FPG (<4.0 mmol/L) is a likely driver of this pattern. Systematic reviews indicate that decreased FPG contributes to both a higher incidence of all-cause mortality and an increased likelihood of cardiac events (48). Furthermore, studies examining different metabolic patterns have confirmed a significant association between AKI and the low glucose/high lactate metabolism pattern (49). We speculate that hypoglycemia may impair insulin sensitivity and energy metabolism (50, 51), ultimately adversely affecting renal function and contributing to the development of AKI.

For subgroups with a TyG index ≥ 8.602, the within-subgroup association between TyG and AKI risk was attenuated without vasopressor or insulin therapy (HR 1.24, 0.91–1.68; HR 1.33, 0.97–1.81, respectively) but was markedly steeper among those receiving vasopressor therapy (HR 3.88, 1.60–9.43) or insulin therapy (HR 4.06, 1.69–9.77). This discrepancy may be attributed to the differing pathophysiological states of the two groups. Patients not receiving vasopressors typically exhibit better circulatory stability, suggesting less severe underlying disease and relatively intact compensatory hemodynamic mechanisms, which may mitigate the metabolic damage to the kidneys associated with an elevated TyG index. Additionally, patients receiving insulin therapy inherently display more pronounced metabolic disturbances, particularly in the context of poor FPG control. IR and inadequate FPG control may lead to a series of metabolic issues that can increase renal burden, thereby escalating the AKI incidence. However, these treatment-stratified findings should be interpreted with caution given the small number of events and wide confidence intervals in treated subgroups and the potential for confounding by indication.

This study, utilizing a long-term cohort dataset from PIC database (2010–2019, n=2298), strengthens the reliability of its findings through a large sample size and multidimensional sensitivity analyses, including an E-value analysis. The decade-long time frame may aid generalizability; nevertheless, several limitations warrant caution. First, due to the study’s retrospective and observational design, it cannot confirm clear causal links, although it identifies the relationship between the TyG index and AKI. Second, relying on data from a single research facility may introduce selection bias, limiting the applicability of the conclusions to populations from other institutions or adult patients. Third, despite E-value analyses, residual confounding may persist and could affect effect estimates. Fourth, the precision of the severe AKI estimate was limited (HR 2.75; 95% CI 1.18–6.42), due to the lower event count. therefore, this finding should be interpreted with caution. Finally, the absence of longitudinal data on long-term renal outcomes precluded evaluating the TyG index’s prognostic value for chronic kidney dysfunction. These limitations highlight the need for multicenter prospective cohorts with serial metabolomic profiling and extended follow-up to clarify mechanisms linking the TyG index to AKI.

This study shows a nonlinear, U-shaped association between the TyG index and AKI in children with cardiac disease, with an inflection point at 8.602. This finding supports the potential use of TyG for bedside risk stratification in pediatric cardiac care and may provide a simple, actionable indicator to identify children at increased risk of AKI.