In this study, we confirmed a notable correlation between the TyG index and the risk of RFD. The results indicate that individuals exhibiting a high TyG index are at an increased risk of experiencing future RFD, in contrast to those with a low TyG index. Additionally, the relationship between the TyG index and renal events suggests that IR could play a pivotal role in the onset of RFD. In line with our result, Yoshida et al. conducted an analysis involving data from 10,758 Japanese individuals. Future RFD was characterized as a decrease of ≥ 25% in eGFR from the baseline measurement. Throughout the follow-up duration (37.8 ± 23.6 months), the incidence rates of RFD were recorded at 0.31 and 0.69 per 100 person-years for the low and high TyG index groups, respectively. Furthermore, a high TyG index was found to be significantly correlated with future RFD, with a HR of 2.25 and a 95% CI of 1.40–3.6013. Chen et al. examined data from 548 Taiwanese participants with hypertension. RFD was defined as a decline of > 25% in eGFR. Over an average follow-up period of 4.7 ± 3.1 years, 97 patients experienced a decline of > 25% in eGFR. The findings indicated that the TyG index (HR = 1.490; 95% CI = 1.016–2.185, P = 0.041), office SBP (HR = 1.013; 95% CI = 1.000–1.026, P = 0.047), diabetes mellitus (HR = 1.797, 95% CI = 1.026–3.147, P = 0.040), and baseline eGFR (HR = 1.015; 95% CI = 1.002–1.028, P = 0.025) were all significantly associated with RFD. In addition, patients with eGFR decline (> 25%) exhibited remarked elevated levels of the TyG index compared with patients who did not experience eGFR decline (P = 0.014)12. Lei et al. explored the association between the TyG index and eGFR in a cohort study including 7,822 elderly adults from South China. Their results showed that the TyG index is significantly associated with 30% decline of eGFR (HR per SD increase:1.38; 95% CI: 1.26–1.50), or 40% decline of eGFR (HR per SD increase: 1.42; 95% CI: 1.24–1.63)16. Liu et al. conducted an analysis involving data from 3,899 participants in the China Health and Retirement Longitudinal Study. The main outcome measured was rapid kidney function decline (RKFD), which is characterized as an annualized decrease in eGFRcr-cys of 5 ml/min per 1.73 m2 or greater. Over a follow-up period of 3.99 years, 191 instances of RKFD were documented. The TyG index and its related two indices (triglyceride-glucose × BMI (TyGBMI), and triglyceride-glucose × waist circumference (TyGWC)) showed significant associations with the occurrence of RKFD, with TyGWC demonstrating the highest predictive capability for RKFD17. CKD is the primary cause of sustained, pathological eGFR decline. A sustained decrease (especially below 60 mL/min/1.73 m2 for more than 3 months) is the defining feature of CKD18. Numerous studies have shown that a high TyG index is associated with the risk of CKD. Regarding this, Ren et al. investigated the relationship between the TyG index and CKD in a cohort study including 10,498 subjects, their results showed that the HR (95% CI) for the highest quartile compared to the lowest quartile of TyG index was 1.30 (1.08–1.57). Furthermore, each SD increase in the TyG index was linked to an 11% higher risk of new-onset CKD (HR: 1.11, 95% CI: 1.03–1.19)19. Okamura et al. studied the association between the TyG index and incident CKD in a cohort study including 11,712 participants in Japan, they demonstrated that a higher TyG index was significantly associated with risk for incident CKD in both men (HR: 1.32, 95% CI 1.02–1.70, P = 0.036) and women (HR: 1.50, 95% CI: 1.05–2.13, P = 0.024)20. Liu et al. conducted an analysis involving data from 4361 participants who were part of the National Health and Nutrition Examination Survey conducted between 2015 and 2018. The average TyG index recorded was 8.60 ± 0.68, while the prevalence of CKD was found to be 13.35%. It was observed that participants exhibiting a higher TyG index were linked to an increased risk of CKD (OR = 1.34, 95% CI: 1.13, 1.59, P = 0.0006)21.

Furthermore, our results also identified that a stronger association between the TyG index and the risk of RFD in individuals aged less than 60 years compared to those above, in women compared to men. Considering age as a significant risk factor for RFD22, the influence of TyG index appeared to diminish in the ≥ 60 years cohort after stratification and adjustment for age-related covariates. This reduction may be due to the prevalence of comorbidities, including cardiovascular diseases. An increasing amount of evidence suggests that IR plays a role in RFD23. IR is highly prevalent in CKD due to chronic inflammation, where increased proinflammatory cytokines impair insulin signalling24. In cases of IR, a low-grade inflammatory response is triggered, leading to heightened macrophage infiltration in both adipose tissue and the kidney. This macrophage infiltration results in the generation of various pro-inflammatory cytokines and subsequent elements. Elevated pro-inflammatory cytokines, particularly interleukin-6, and activation of the NFκB pathway drive renal injury, metabolic dysfunction, and cardiovascular complications25. Moreover, recent findings have provided substantial evidence to support the significant involvement of insulin in the function of the glomerular filtration barrier26. Additionally, insulin could play a role in the progression of microalbuminuria and CKD by impacting the production of transforming growth factor β in mesangial and proximal tubule cells27. Studies have indicated that transforming growth factor β production leads to heightened fibrosis in the interstitium and podocyte remodeling, ultimately leading to increased extracellular matrix production and damage to the filtration barrier, which are factors potentially involved in the development of microalbuminuria28. Therefore, it is crucial to aggressively manage metabolic abnormalities including IR/hyperinsulinemia to prevent or delay the progression of renal function loss and the development of CKD7.

Our study has some limitations. First, the study endpoint was a future RFD, which was defined as a 25% decrease in eGFR from baseline to below 60 ml/min/1.73 m2. CKD is the primary cause of sustained, pathological eGFR decline18. However, with a biennial examination schedule, it is impossible to distinguish between CKD and acute kidney injury (AKI). CKD is defined as the existence of kidney impairment or an eGFR below 60 ml/min/1.73 m2, enduring for a period exceeding 3 months. In CKD, the body undergoes gradual adaptations to sustain GFR and achieve a balance of creatinine and various electrolytes. Conversely, AKI represents a sudden deterioration in kidney function, typically occurring within a matter of hours or days, characterized by increased serum creatinine levels and diminished urine output. During AKI, these adaptive mechanisms frequently fail to take place, leading to a swift advancement towards renal failure5. In addition, the existence of albuminuria or proteinuria indicates kidney damage and, when combined with the assessment of GFR, forms the basis for evaluating CKD. Unfortunately, proteinuria/albuminuria data were not incorporated in the current study. While the supplementary sensitivity analysis, involved excluding all-cause death during the follow-up period, was performed, it does not entirely alleviate the concern that death could serve as a competing event in the analysis of long-term renal outcomes. The primary time-to-event analyses consider death as a form of censoring, which may consequently lead to an overestimation of the cumulative incidence of RFD. Lastly, given that our study population is 80.38% male, which substantially differs from typical community-based populations, the results could not be generalized to the general population of North China.