It has been recognized that there is an association between the ear and the kidney16,17. However, most studies have concentrated on individuals with genetic abnormalities to explore this relationship6,17. Studies investigating the link between moderate CKD and presbycusis are notably scarce. This study primarily aimed to assess how moderate CKD correlates with low-frequency HI, high-frequency HI, and HI grades. Additionally, it aimed to investigate how the inflammatory biomarker NPAR mediates the link between moderate CKD and presbycusis for the first time.
We observed that out of 939 participants, 263 (27%) exhibited moderate CKD, while 676 (73%) demonstrated an eGFR ≥ 60 mL/min/1.73 m2. For low-frequency PTA, 52.61% of the participants exhibited normal hearing, 33.17% demonstrated slight HI, and 14.27% experienced moderate and severe HI. In contrast, for high-frequency PTA, only 7.99% of the participants exhibited normal hearing, 26.09% experienced slight HI, and the majority (65.92%) demonstrated moderate and severe HI. These findings were consistent with previous studies reporting that HI is generally more severe in the high-frequency range, especially in elderly populations18. This disparity further underscores the significance of high-frequency HI as a marker of presbycusis, especially in individuals with CKD.
To address the issue of uneven sample sizes across different frequency HI categories, we conducted a power analysis for both low- and high-frequency HI categories. For low-frequency PTA, the power was 0.996 for a medium effect size (f = 0.25) and 0.956 for a small effect size (f = 0.20), indicating that even small effects can be detected with high probability. This suggests that the low-frequency analysis is robust in detecting differences across the HI categories. For high-frequency PTA, the power for a medium effect size (f = 0.25) was 0.926, which is sufficient to detect moderate effects. However, for a small effect size (f = 0.20), the power was 0.765. Although this is lower, it still provides reasonable power to detect small effects. It is important to note that the sample size for normal-hearing participants in the high-frequency PTA was considerably smaller, which may have contributed to the lower power for detecting small effects.
The relationship between kidney function and HI has been a subject of growing interest, particularly in understanding how CKD affects auditory health. When examining the relationship between kidney function and HI in the context of low-frequency PTA, we observed that participants with an eGFR ≥ 60 mL/min/1.73 m2 and moderate CKD predominantly exhibited normal hearing. Conversely, in the high-frequency PTA, individuals with eGFR ≥ 60 mL/min/1.73 m2 and moderate CKD tended to experience moderate and severe HI. Furthermore, the prevalence of moderate CKD patients with moderate and severe HI increased progressively with age. These findings suggest that high-frequency hearing may be more sensitive to the underlying pathophysiological processes associated with CKD, consistent with previous studies linking renal dysfunction to the auditory system19.
A key finding in our study was that the association between moderate CKD and low-frequency HI was confounded by age, gender, and race. In our initial model, a significant relationship between CKD and low-frequency HI was observed, but after adjusting for these demographic factors, the association lost significance. This implies that factors such as age and gender may play a more substantial role in low-frequency HI than previously understood. In contrast, the association between moderate CKD and high-frequency HI remained significant after adjusting for all covariates. Moreover, among high-frequency PTA participants, moderate CKD increased the risk of slight HI (OR = 5.13, 95% CI = 1.48–17.86, and P = 0.01) and moderate and severe HI (OR = 4.68, 95% CI = 1.29–17.04, and P = 0.02). This suggests that high-frequency HI is more directly and robustly related to the pathophysiology of moderate CKD. These findings were consistent with the results reported by Vilayur et al.19, where they found that after adjusting for all covariates, moderate CKD was significantly associated with moderate HI (OR = 1.46, 95% CI: 1.11–1.92, and P = 0.007) and increased the risk of severe HI (OR = 1.50, 95% CI: 1.04–2.18, and P = 0.03).
Furthermore, a longitudinal population-based study by Schubert et al.20 revealed a close association between eGFRCysC (an indicator of renal function) and HI in the elderly. Participants with eGFRCysC < 60 mL/min/1.73 m2 exhibited a potentially higher 20-year cumulative incidence of HI compared with those with eGFRCysC ≥ 60 mL/min/1.73 m2 (HR = 1.50 and 95% CI: 1.02–2.22). Although previous research has shown that CKD is associated with high-frequency HI, and its severity is closely related to age21, the relationship between eGFR and HI remains a topic of debate. A study on the Chinese population by Yang et al.22 found that higher eGFR levels increase the risk of HI and HI grades in individuals aged 45–65. However, no association was found between eGFR and HI in women and individuals aged ≥ 65, which contradicts our findings. Meanwhile, Gupta et al.23 also found no significant association between CKD and the risk of incident HI. This disparity may be attributed to factors such as race, dietary habits, geographical region, and others. Consequently, these differences suggest that the relationship between CKD and HI may vary across different populations or regions. Therefore, future studies should validate these hypotheses and take into account factors such as race, lifestyle, and geographical differences.
To our understanding, systemic inflammatory cells such as neutrophils and albumin have been linked not only to presbycusis15,24 but also to moderate CKD14. Elevated levels of neutrophils promote free radical aggregation, intensifying inflammatory responses and oxidative stress25, which exacerbate the progression of presbycusis. Conversely, albumin is believed to exhibit a negative correlation with inflammatory responses and oxidative stress, potentially slowing down the advancement of presbycusis24,26,27.
In addition, neutrophils can cause irreversible kidney damage by inducing the secretion of various inflammatory mediators, thereby further reducing and worsening kidney function. Hypoalbuminemia may accelerate renal endothelial cell damage by altering microcirculatory blood flow and increasing blood viscosity, potentially increasing morbidity and mortality in CKD patients14,28. Moreover, eGFR was found to decrease with increasing neutrophil levels and increase with increasing albumin levels29. NPAR is a new systemic inflammation marker, calculated from the neutrophil-to-albumin ratio, useful for predicting outcomes in various inflammation-related diseases. It has notably demonstrated a significant association with coronary atherosclerosis in older adults with CKD patients aged ≥ 65 years30.
However, no study has yet explored the relationship between the NPAR in moderate CKD and presbycusis. Based on previous studies, we investigated whether the inflammation index NPAR contributes to the association between moderate CKD and presbycusis. In this study, we confirmed a significant linear positive correlation between NPAR and high-frequency PTA (R = 0.19, P < 0.001), as well as a significant linear negative correlation between NPAR and eGFR of moderate CKD (R = –0.12, P < 0.044). When NPAR was divided into quartiles, participants in the highest quartile (Q4) exhibited a higher risk of high-frequency HI (OR = 1.42, 95% CI: 1.06–1.91, and P = 0.018) and moderate CKD (OR = 2.73, 95% CI: 1.09–6.86, and P = 0.03). We further evaluated the mediating role of NPAR between moderate CKD and high-frequency HI. Notably, through mediation analysis, NPAR was found to significantly mediate the association between moderate CKD and presbycusis, with a mediation ratio of 17.85%.
The strength of this study lies in its examination of the relationship between HI grades and both low-frequency PTA (0.5, 1, and 2 kHz) and high-frequency PTA (3, 4, 6, and 8 kHz). Unlike most previous studies that analyzed this relationship using only the average audiometric thresholds at 0.5, 1, 2, and 4 kHz19,20,22, this study provided a more comprehensive assessment. A key innovation of this study is its potential to be the first to assess how NPAR mediates the link between moderate CKD and presbycusis risk.
Our study has several limitations. First, the complex pathogenesis of presbycusis induced by moderate CKD involves multiple pathways, including inflammation, apoptosis, autophagy, and oxidative stress. This study exclusively focused on the role of the inflammation-related indicator NPAR in the correlation between moderate CKD and presbycusis. In the future, the specificity of NPAR should be validated through multiple biomarker analyses, such as simultaneous binding of NPAR, CRP, and fibrinogen, to enhance the understanding of its role and to refine the diagnostic and therapeutic implications of NPAR in this context. Meanwhile, future research should explore additional mechanisms linking moderate CKD to presbycusis. Second, potential confounding variables were not fully controlled for, and the generalizability of the findings may be affected by factors such as regional, lifestyle, or demographic differences. While we conducted rigorous statistical analyses to minimize the influence of known confounders, we acknowledge that unmeasured confounders may still be at play. In future research, a more robust multivariate model controlling for a wider range of confounders, including lifestyle factors and comorbidities, should be employed to better understand the generalizability of our findings across different populations. Finally, the retrospective and cross-sectional design of this study limits our ability to establish causality. Given that the data were collected at a single point in time, it is difficult to determine whether moderate CKD causes presbycusis or if there are other underlying factors contributing to both conditions. To overcome this limitation, we propose that future studies adopt longitudinal or prospective cohort designs. These designs would allow for the tracking of CKD progression and its association with changes in auditory function over time, providing stronger evidence for a causal relationship.
Despite these limitations, this study provides important insights into the relationship between moderate CKD and presbycusis. By identifying inflammation-related markers like NPAR, we highlight potential targets for early diagnostics and interventions to prevent or mitigate HI in CKD patients. Further validation in larger, diverse populations is needed, and prospective studies will be essential to confirm the clinical relevance of these findings.