The deleterious effects of added sugars have been established for multiple health outcomes, and recognized as major risk factors by several health authorities, such as World Health Organization (WHO) (1). As the main source of added sugars in the diet, sugar- sweetened beverages (SSBs) have been linked to with several chronic diseases, such as obesity, type 2 diabetes, certain cancers, cardiovascular disease, and mortality (2–5). A recent study based on the Global Burden of Disease (GBD) 2019 showed that the number of deaths for chronic non-communicable diseases attributed to high SSBs increased from 149,988 in 1990 to 242,218 in 2019, representing a 61% increase (6). Artificially sweetened beverages (ASBs) and natural juices (NJs, 100% pure fruit or vegetable juices) are considered alternatives to SSBs, but their long-term effects on human health are still controversial (7–12). Evidence from systematic reviews and meta-analyses has suggested that higher consumption of ASBs was associated with risk of obesity, hypertension, type 2 diabetes, and all-cause mortality (10–12).

Chronic Kidney Disease (CKD) is a major global public health concern with an increasing prevalence and massive socio-economic impact (13). The study based on GBD data showed that the global prevalence of CKD was 9.1% in 2017, causing 35.8 million disability-adjusted life years and 1.2 million deaths (13). CKD is a complex condition that results from various genetic, environmental, and behavioral factors, such as unhealthy lifestyles, hypertension, obesity, and diabetes mellitus (14). Although higher consumption SSBs and ASB have been linked to CKD risk factors (i.e., obesity, hypertension, and diabetes), their prospective associations with CKD have not yet been well-established due to inconsistent findings of previous studies (15–17).

Previous studies examining the associations of the consumption SSBs and ASBs with CKD risk have yielded contradictory and inconsistent findings (15–19). For example, two prospective studies in the US and Iran found positive associations between higher consumption SSBs and the risk of incident CKD (19, 20), while other studies based on the Atherosclerosis Risk in Communities and Nurses' Health Study in U.S. showed no significant association of SSBs with CKD risk (21, 22). A meta-analysis in 2021 indicated that higher consumption SSBs or ASBs was associated with a non-significant increased risk of CKD (SSBs, RR 1.30, 95% CI 0.88–1.94, n = 6 studies; ASBs, RR 1.40, 95% 0.65–3.02, n = 3 studies) (15). However, the studies found that the risk of CKD significantly increased if the SSBs or ASBs intake exceeded seven servings per week (15). Differences in study design and participants, sample sizes, definitions and measurements of exposure might explain the inconsistent findings, making it difficult to draw definitive conclusions regarding beverages consumption and CKD risk.

Furthermore, the biological pathway underlying the association between beverage consumption and CKD risk remains unclear. Given the causal role of metabolic risk factors such as obesity and hypertension in the CKD development, and the well-established association of SSBs or ASBs intake with these metabolic risk factors, the substantial mediation of the SSBs or ASBs effect through the metabolic risk factors seems biologically plausible. However, no study to date has examined the potential mediation effect of metabolic risk.

In the present study, we conducted a prospective analysis of the UK Biobank cohort to evaluate the long-term association of SSBs, ASBs, and NJs with incident CKD. We further estimated to what extent the metabolic syndrome (MetS) and its individual components mediated the observed associations of different types beverages with CKD risk.

Among 191,956 participants included in the analysis, 62,453 (32.6%) drank SSBs, 22,790 (11.9%) drank ASBs, and 63,318 (33.0%) drank NJs. Participants who consumed more SSBs were more likely to be younger, male, deprived, smokers, had a higher daily total energy and sugar intake, and a higher prevalence of MetS (Table 1). Meanwhile, those who consumed more ASBs tended to be younger, female, deprived, more highly educated, with a higher prevalence of medication use (e.g., aspirin, proton pump inhibitors) and MetS (Supplementary Table 2). Additionally, NJs consumers tended to be male, more educated, have higher income, be non-smokers, and have higher daily total energy and sugar intakes (Supplementary Table 3).

During a median follow-up of 10.63 years, we documented 4,983 incident CKD cases. Table 2 presents associations of SSBs, ASBs, and NJs with the risk of CKD. After adjusting for sociodemographic factors, lifestyle behaviors, medication use, total sugar and energy intake, and two other beverages, all three types of beverages were associated with the risk of CKD. In the fully adjusted model, participants consuming >1 units/d of SSBs had a 45% higher risk of CKD compared with non-consumers (HR 1.45; 95% CI 1.30–1.61, P-trend < 0.001). Higher ASBs intake was also associated with a higher CKD risk (P-trend < 0.001), with HRs of 1.14 (95% CI 1.05–1.23) for >0–1 unit/d and 1.52 (95% CI 1.36–1.70) for over 1 unit/d compared to non-consumers. In contrast, participants with moderate NJ intake (>0–1 unit/d) had a 14% reduced CKD risk (HR 0.86, 95% CI 0.81–0.91) compared with non-consumers. We did not observe sufficient evidence of associations for consuming SSBs 0–1 unit/day or NJs >1 units/day compared to none (Table 2). We also found that participants consuming 0.5–1 unit/day of SSBs or ASBs were at a higher risk of CKD (HR 1.09, 95% CI 0.99–1.19 for SSBs; HR 1.31, 95% CI 1.18–1.46 for ASBs), while those consuming 0–0.5 unit/day of SSBs or ASBs did not show an increased risk compared to non-consumers (Supplementary Table 4). In substitution analyses, replacing 1 unit/d of SSBs or ASBs with an equivalent consumption of NJs was associated with a nearly 20% lower risk of CKD (HR 0.82, 95% CI 0.77–0.87 for SSBs; HR 0.80, 95% CI 0.75–0.85 for ASBs). However, substituting SSBs with ASBs did not reduce the risk of CKD (HR 1.02, 95% CI 0.97–1.08).

In the restricted cubic splines, we observed a significant non-linear relationship between SSBs and NJs to CKD risk, but not for ASBs (P-non-linearity = 0.005 for SSBs, <0.001 for NJs, and 0.989 for ASBs, Figure 1 and Supplementary Figure 2). Higher SSBs intake was associated with a substantially increased CKD risk, but only if SSBs intake was above >0.5 units/day. In addition, we observed a J-shaped association between NJs and CKD risk, with the lowest risk at 0.5 unit/day.

In this prospective analysis of over 0.19 million participants, we found that SSB intake of >1 units/day or ASB intake of >0 units/day was each associated with a higher risk of CKD, whereas moderate NJs consumption (0–1 unit/day) was associated with a lower risk. These associations were robust across major subgroups and in sensitivity analyses. Moreover, we found that over 10% of the total association of CKD with SSBs or ASBs consumption was partly mediated through MetS. Regarding individual components of MetS, central obesity mediated the highest proportion of the observed associations of CKD with SSBs or ASBs consumption. These findings highlight the importance of controlling excessive SSB or ASB consumption for CKD prevention. Furthermore, the findings identified the MetS processes as a potentially influential pathway linking SSBs or ASBs consumption to CKD risk.

Previous studies regarding the associations between sugary beverages and CKD have yielded inconsistent results (15–22). Consistent with our findings, a prospective cohort study based on Jackson Heart Study found that higher consumption of SSBs was associated with an increased risk of CKD (OR 1.18, 95% CI, 1.00–1.39) (19). Another study based on the Nurses' Health Study (NHS) indicated that consuming artificially sweetened soda was associated with nearly a 2-fold higher risk of eGFR decline ≥30% compared with consuming <1 servings per month over the 11 years of follow-up (OR 2.02, 95% CI 1.36–3.01), but whereas the association was non-significant for sugar soda (OR for ≥ 1 servings per day vs. <1 servings per month = 1.56, 95% CI 1.84–1.91) (21). In contrast, a cohort study based on the Atherosclerosis Risk in Communities (ARIC) Study showed no association between sweetened beverages and CKD risk (P-trend = 0.30) (22), while a prospective analysis based on the Tehran Lipid and Glucose Study (TLGS) showed a negative association (quintile 5 vs. quintile 1, OR 0.54, 95% CI 0.32–0.94) (18). A recent meta-analysis revealed no association between higher consumption SSBs or ASBs and CKD risk, but reported a higher CKD risk in participants consuming SSBs or ASBs over seven servings per week (15). Given the differences in measurements of beverages, sample size, and cultural background across studies, our findings not only contribute to the current literature in a UK context but also provide further evidence supporting the potential association of SSBs and ASBs with a higher risk of CKD.

As a potential alternative drink for SSBs and ASBs, we found that moderate intake of NJs was associated with a lower risk of CKD, which was in contrast with a previous study that found no association between NJs and CKD risk (19). Furthermore, our substitution analyses showed replacing 1 unit/d of SSBs or ASB with an equivalent consumption of NJs was associated with a nearly 20% lower risk of CKD. Given that the moderate intake of NJs has been linked to a lower risk of central obesity (33), cardiometabolic multimorbidity (34, 35), and dementia (24), our findings suggest that moderate consumption of pure fruit/vegetable juices may be a healthier alternative to SSBs and ASBs for CKD prevention. However, the results from restricted cubic splines suggested participants taking NJ >6 units/d had a higher CKD risk compared those who did not drink any. Since excessive NJs consumption has been linked to a higher risk of weight gain, type 2 diabetes, and increased all-cause mortality (12, 36, 37), further research on fruit juice is warranted to define the optimal intake level.

To our knowledge, this is the first study to investigate that the association between sugar beverages and increased CKD risk may be partly mediated via MetS. Previous studies focused predominantly on the main effect of sugar beverages on CKD risk, neglecting the possibility of multiple pathways and processes (e.g., MetS) linking them (18–22). Our findings, indicating that MetS and its components partially mediate the associations of sugary beverages with CKD risk, offer insights into the mechanisms linking these beverages to CKD development. Notably, higher consumption of SSBs and ASBs has consistently been associated with an elevated risk of obesity, hypertension, diabetes, and MetS (12, 38–40), and MetS and its components were well-established risk factors for CKD (41). This confirmed the observed associations in the study were biologically plausible. Moreover, our findings extend previous research on individual MetS components, such as obesity, which has been shown to mediate the association between sugary beverages and diabetes and cardiovascular disease (42–44). However, given the relatively small mediation proportion of MetS and its individual components, the effect of SSBs and ASBs on CKD is likely explained largely through mechanisms other than MetS, such as chronic low-grade inflammation (20, 45). Further research is needed to explore these mechanisms comprehensively.

The strengths of the present study included data from a well-characterized prospective cohort with large sample size and long-term follow-up, as well as detailed information on sugar beverages, MetS and incident of CKD. The sensitivity and subgroup analyses have confirmed the validity of the findings. In addition, our mediation analyses based on the counterfactual framework provided clues for the underlying mechanisms connecting sugar beverage consumption to CKD risk.

This research has certain limitations. Firstly, sugar beverage consumption was assessed through 24-h diet recall questionnaires, which might be susceptible to recall or reporting biases. Secondly, despite adjusting for several potential confounding factors, the potential for residual confounding from unknown or unmeasured factors cannot be completely ruled out. Thirdly, while efforts were made to minimize reverse causality by lagging the exposure for 2 years, its possibility still exists. Fourthly, as the study participants were primarily from the UK Biobank, and the majority were of white ethnicity, the generalizability of the findings to other racial groups requires further investigation. Fifthly, the observational nature of this study limited our ability to establish causal relationships. Lastly, mediation analysis assumes temporal causation between sugary beverage intake and MetS development, despite both the sugary beverages intake and MetS development were measured at the same time in the UK Biobank. More research with longitudinal data is needed to validated our findings.

This large cohort study found that higher intake of SSBs and ASBs was associated with an increased CKD risk, whereas moderate intake of NJs have protective effect on CKD development. The observed associations partially mediated by MetS. Although the causal relationship cannot be established, our results emphasize the critical importance of limiting the consumption of SSBs or ASBs for CKD prevention. Further research is needed to confirm our findings and explore the optimal intake level for the natural juices.