Chronic kidney disease (CKD) has emerged as a major global public health challenge, primarily driven by its steadily rising prevalence, high rates of disability and mortality, and strong association with cardiovascular events (1, 2). Concurrently, the global obesity epidemic has intensified markedly over the past two decades (3). Notably the parallel trends in prevalence of CKD and obesity have prompted in-depth investigation into their potential interconnection.

Substantial evidence confirms the obesity as a major risk factor for the development and deterioration of CKD (4). A meta-analysis encompassing over 630,000 participants demonstrated that obesity elevates the risks of albuminuria and renal function decline by 51 and 28%, respectively (5); Furthermore, another meta-analysis further revealed that obese individuals face an 83% higher risk of developing kidney disease compared to those with normal weight (95% CI: 1.57–2.13) (6). The association between obesity and CKD is largely mediated by hypertension: research has shown that obesity as a significant risk factor for hypertension (7, 8), which involves mechanisms such as sympathetic nervous system (SNS) activation, renin-angiotensin-aldosterone system (RAAS) overactivity, and induction of insulin resistance. These alterations not only directly promote the development of hypertension but also lead to glomerular hypertension, hyperfiltration, and microvascular damage, accelerating the onset and progression of CKD (9). More pivotally, systolic blood pressure (SBP) has been demonstrated to exert independent and cumulative adverse effects on both microvascular and macrovascular complications in CKD (10), further establishing the critical mediating role hypertension of in the obesity–CKD relationship.

However, current understanding of the “obesity–hypertension–CKD” pathway remains limited both in practical application and mechanistic insight. On the practical level, direct measurement of visceral adipose tissue (VAT) through gold-standard methods such as computed tomography or magnetic resonance imaging remains costly and technically complex, which significantly limits its applicability for large-scale population screening. Furthermore, traditional anthropometric measurements [e.g., body mass index (BMI), waist circumference (WC)] for detecting visceral obesity remains limited, highlighting the need to incorporate additional parameters to strengthen their practical utility. On the mechanistic level, although existing evidence suggests a mediating role of blood pressure in the VAT–CKD association (11), direct evidence regarding its mediation in relationships involving novel adiposity indices remains scant. These critical limitations have stimulated the development of novel adiposity indices for early identification of individuals at high-risk of CKD, with the Visceral Adiposity Index (VAI) and Body Roundness Index (BRI).

Specifically, VAI is a functional composite measure that integrates WC, BMI, triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C). This multi-parameter integration enables VAI to not only reflect the accumulation of VAT but also accurately to assess the metabolic activity and functional status (12). Evidence indicates that the VAI is an independent risk marker for CKD (13). It also shows potential in predicting CKD pathogenesis and is negatively associated with estimated glomerular filtration rate (eGFR) (14). And BRI is an anthropometric index derived from height and WC measurements. It estimates body fat distribution, has been validated as a reliable surrogate marker of visceral fat accumulation and central obesity (15). BRI is an independent marker of CKD risk in individuals with diabetes and may reflect contributions from glycaemic control, kidney function, and nutritional status (16). These two indicators are also significantly associated with the risk of various diseases, including cardiovascular disease (CVD), hypertension, type 2 diabetes, and metabolic syndrome, exhibiting superior performance in risk prediction compared to traditional anthropometric measures such as BMI and WC (17–21). A key advantage of these two indices lies in their practicality: they can be calculated directly from standard clinical measurements, without necessitating any specialized assessments, making them straightforward to implement and standardize, and making them well-suited for implementation in primary healthcare settings and large-scale epidemiological studies. While the associations of VAI and BRI with CKD have been established in other populations (e.g., the US), evidence from Chinese cohorts, particularly southern Chinese populations, remains scarce. Moreover, the potential mediating role of blood pressure, in the VAI/BRI–CKD association has yet to be quantified.

Therefore, this study aims to address these gaps by leveraging cross-sectional survey data from the Hakka population in Bobai County, Guangxi, which is an ethnic subgroup of the Han ethnicity. Specifically, the study will investigate the prevalence and distribution characteristics of CKD in this population, examine the associations between VAI/BRI and CKD. Furthermore, we will quantitatively assess the mediating effects of blood pressure indicators in these associations and systematically compare potential differences in the mediating pathways between the two adiposity indices. We hope that our research can provide new insights into the treatment and prevention of CKD and offer theoretical support for clinical decision-making.

This cross-sectional study investigated the prevalence of CKD among adult population in Bobai County, Guangxi. The results revealed the prevalence of CKD in this population was 12.62% (95% CI: 11.94–13.33%), exceeding the 8.2% prevalence reported by Wang et al. (23) in the general Chinese adult population. This discrepancy may be attributed to regional differences in lifestyle (e.g., dietary patterns, physical activity levels), socioeconomic factors, or the high prevalence of metabolic comorbidities (e.g., obesity, hypertension) in the study population, underscoring the urgent need to identifying high-risk subgroups and implement precision prevention strategies for CKD in this region.

Within this epidemiological context, we identified significant positive associations between both VAI and BRI with CKD risk, demonstrating clear dose–response relationships. These findings are consistent with the growing body of evidence linking visceral adiposity to renal injury. For instance, a large retrospective cohort study confirmed that various visceral adiposity indices, including VAI and BRI, were significantly associated with both CKD risk and rapid kidney function decline (24). Zheng et al. (13) reported that higher VAI quartiles were associated with progressively elevated CKD: compared to the lowest quartile (reference), the relative risks for Q2, Q3, and Q4 were 2.24 (95%Cl: 1.70–2.95), 2.36 (95%Cl: 1.54–3.61), and 2.57 (95%Cl: 1.57–4.22), respectively. Furthermore, Fei et al. (24) demonstrated that each unit increase in BRI was associated with 10.5% higher odds of CKD (OR: 1.109; 95% CI: 1.040–1.183).

Collectively, these data support the notion visceral fat accumulation is a critical driver in CKD development and progression. For instance, visceral obesity has been established as a key risk factor for both CKD development and progression to end-stage renal disease (ESRD) (4). Notably, Peng et al. (25) innovatively proposed that the central obesity index Metabolic Score for Visceral Fat (METS-VF) is an independent risk factor for CKD, with CKD prevalence increasing significantly across METS-VF tertiles. On the contrary, lifestyle interventions targeting visceral obesity, such as dietary modification and increased physical activity, have been shown to slow CKD progression (26, 27). Our study extends these findings by validating the utility of VAI and BRI in southern Chinese adults, offering localized evidence to guide population-specific kidney disease prevention protocols.

The glomerulus is the primary early site of injury in obesity-related kidney disease, where mechanisms including insulin resistance, chronic inflammation, lipotoxicity, and hemodynamic alterations (28, 29). These mechanisms induce intraglomerular hypertension and hyperfiltration, leading to direct podocyte injury and disruption of the filtration barrier (30). This results in increased glomerular permeability, which is clinically detected as albuminuria (elevated UACR). A pivotal renal biopsy study of 95 severely obese patients with normal renal function undergoing bariatric surgery substantiates this mechanism, revealing characteristic early lesions (glomerulomegaly, podocyte hypertrophy, and mesangial cell proliferation) (31). During this stage, nephron compensation maintains normal eGFR, whereas UACR can sensitively detect such subclinical renal injury. In contrast, from a diagnostic standpoint, a marked decline in eGFR typically indicates more advanced structural damage (extensive glomerulosclerosis and interstitial fibrosis). However, that in a minority of conditions where the primary pathology targets the renal tubulointerstitium, a decline in eGFR can be the initial and predominant clinical manifestation, independent of significant albuminuria. Consistent with this pathological framework, our results demonstrated a more pronounced association between VAI/BRI and CKD defined by UACR≥30. Taken together, increased glomerular permeability is an early, pivotal event in obesity-related nephropathy that precedes and is partly independent of later GFR decline. This highlights the importance of prioritizing UACR screening in obese populations for the early intervention of CKD.

Among these, hypertension as a key manifestation of hemodynamic dysfunction, serves as a critical mediator linking visceral adiposity to renal injury. Experimental studies confirm that early-stage intra-glomerular hypertension and hyperfiltration are observable in obese animal models (32), validating the central role of blood pressure mechanisms. Our mediation analysis provides critical quantitative evidence and novel mechanistic insights into the blood pressure pathway. Our findings not only confirm the crucial mediating role of blood pressure indicators in the pathways connecting VAI/BRI to CKD, but also reveal differences between distinct adiposity indices.

For BRI (a purely morphological index reflecting trunk fat accumulation), the mediation proportions of blood pressure were substantially higher: 42.7% (SBP), 51.2% (DBP), and 53.4% (MAP). BRI’s focus on trunk fat likely explains this: trunk fat accumulation directly impacts blood pressure via mechanical compression (e.g., perirenal fat compression) and neuroendocrine activation (e.g., SNS/RAAS stimulation), making MAP (a marker of renal perfusion pressure) the strongest mediator (53.4%). Research has demonstrated that a high BRI is closely associated with hypertension (18). On one hand, substantial visceral and perirenal fat accumulation directly compresses renal parenchyma, increasing renal pressure and inducing medullary hypoxia (33, 34). In the Framingham Heart Study, individuals with high perirenal fat (“fatty kidney”) demonstrated over a two-fold higher risk of hypertension (35). Concurrently, increased intra-abdominal pressure further alters renal hemodynamics and promotes sodium retention (36). On the other hand, adipose tissue, particularly visceral fat, autonomously produces angiotensinogen (37), triggering RAAS overactivation. Increased angiotensin II levels induce vasoconstriction and promote sodium and water retention, raising blood pressure. Experimental models substantiate this pathway: fasting suppresses angiotensinogen expression in rat VAT, while refeeding markedly upregulates its production and elevates blood pressure (38). Similarly, mice with VAT-specific angiotensinogen overexpressing develop hypertension (39). Furthermore, adipocyte-derived mediators such as leptin act on the hypothalamus to induce SNS overactivation, increasing renal vascular resistance and enhancing sodium reabsorption (40). Notably, leptin neutralization or inhibition of hypothalamic leptin receptors normalizes blood pressure in obese rodents. Conversely, leptin-deficient mice and humans with leptin or leptin receptor mutations exhibit lower blood pressure despite severe obesity (41, 42).

In contrast, VAI is a functional composite measure that focuses more on assessing the metabolic activity of VAT. Its relatively lower mediation proportion in the blood pressure pathway (21.4% for SBP, 28.2% for DBP, 28.4% for MAP) suggests that VAI-associated renal injury primarily occurs via non-hypertensive pathways, including more pronounced insulin resistance, direct lipotoxic effects, and chronic inflammatory states. Elevated levels of insulin resistance surrogates (e.g., TYG) are significantly correlated with a higher probability of uncontrolled, resistant, and refractory hypertension and with increased disease severity (43). Additionally, adipose tissue dysfunction induces chronic low-grade inflammation and oxidative stress impairing vascular endothelial function and reducing nitric oxide bioavailability, disrupting blood pressure homeostasis. Several studies have indicated that VAI is more strongly associated with cardiovascular risk and MetS than other anthropometric indices (e.g., WC, BMI, BRI, and WHR) (44–46). Notably, PP (a marker of arterial stiffness) exhibited a significant mediation effect only in the BRI-CKD pathway (12.2%), indicating that BRI-defined central obesity may be closely linked to arteriosclerosis. This association may involve multiple signaling pathways, such as integrin-mediated signal transduction, promoting phenotypic switching of vascular smooth muscle cells phenotypic switching and extracellular matrix remodeling, ultimately leading to vascular wall thickening and reduced elasticity (47).

The observed differences indicate that BRI and VAI may reflect obesity-associated health risks from distinct dimensions. This understanding provides a basis for selecting appropriate risk assessment tools in different practical scenarios. Notably, BRI requires only height and waist circumference, enabling rapid, low-cost, and highly reproducible assessment without laboratory tests. This makes BRI a particularly cost-effective tool for early CKD risk identification in resource-limited or large-scale screening settings (e.g., primary care, epidemiological surveys). In contrast, VAI incorporates lipid parameters, providing additional information on metabolic status. In clinical settings where blood testing is available, it can be used for more comprehensive metabolic risk assessment in high-risk individuals. The two measures are complementary and can serve different stages of prevention and management.

This study has several limitations. First, due to the cross-sectional observational study design, the causal relationships between VAI/BRI, and CKD cannot be fully determined, prospective cohort studies are needed to confirm temporal associations. Second, although multiple confounding factors were adjusted for in our analyses, the potential influence of residual confounding cannot be entirely excluded. Finally, the study did not extensively explore other potential mediators (e.g., inflammatory cytokines, insulin levels, or lipotoxicity-related biomarkers), which may contribute to obesity-related kidney injury. Future research should involve prospective cohort studies or Mendelian randomization analyses to conduct comprehensive multi-mediator analyses, elucidating the full mechanistic spectrum.

In conclusion, our study demonstrates that the novel adiposity indices VAI and BRI are independently associated with CKD risk in southern Chinese adults, even after adjusting for potential confounders. Moreover, mediation analysis further confirms that blood pressure plays a significant mediating role in these associations—with stronger effects observed for BRI than VAI. These findings establish a foundation for the development of targeted CKD prevention and management strategies, can identify high-risk individuals, while blood pressure control may mitigate CKD risk in those with elevated adiposity. Ultimately, this work provides valuable tools to address the growing global burden of CKD.