https://orcid.org/0000-0001-9923-5747
Dear Editor,
We read with great interest the study by Azegami et al. [1], which elucidates the association between decreased estimated glomerular filtration rate (eGFR) and the incidence of obstructive sleep apnea (OSA). This large-scale retrospective cohort study, analyzing over 1.58 million individuals in Japan, provided robust evidence demonstrating a dose-dependent relationship between eGFR reduction and increased OSA risk. The study highlights the need for enhanced screening of OSA in chronic kidney disease (CKD) patients to improve clinical outcomes.
While we appreciate the insights from this research, we believe the relationship between CKD and OSA is likely bidirectional rather than unidirectional. Numerous studies suggest that OSA, through mechanisms such as intermittent hypoxia and sympathetic activation, may accelerate CKD progression. Notably, CPAP (continuous positive airway pressure) therapy has been shown to mitigate CKD progression in OSA patients [2]. In addition, OSA and nocturia interact dynamically, often exacerbating each other. OSA disrupts sleep and alters the secretion of ADH (antidiuretic hormone) and ANP (atrial natriuretic peptide), leading to nocturnal polyuria and increased nocturia frequency [3, 4].
Figure 1 provides a visual representation of these intricate relationships, emphasizing the multifactorial interplay between CKD and OSA. The figure highlights how these conditions are interconnected through pathways such as hormonal imbalances, mitochondrial dysfunction, and circadian rhythm disruption.
Bidirectional pathways linking CKD and OSA. This figure illustrates the bidirectional relationship between CKD and OSA. CKD and reduced eGFR exacerbate OSA through mechanisms such as fluid overload and impaired metabolic regulation. In contrast, OSA accelerates CKD progression via intermittent hypoxia, sympathetic activation, and nocturia mediated by hormonal imbalances, including ANP and ADH dysregulation. The resulting nocturia disrupts the circadian rhythm, influencing the hypothalamic–pituitary axes (HPA, HPG, HPT), and contributes to hormonal dysregulation (e.g. glucocorticoid, testosterone, thyroid hormones). These disturbances impair mitochondrial function, further compromising renal energy metabolism and function.
For middle-aged and older men, benign prostatic hyperplasia further compounds nocturia, creating a vicious cycle of worsening nocturia and impaired circadian rhythm [5]. This disruption of the central circadian clock in the hypothalamus (specifically the suprachiasmatic nucleus, SCN) may dysregulate hormonal axes, including the hypothalamic–pituitary–adrenal (HPA), hypothalamic–pituitary–gonadal (HPG), and hypothalamic–pituitary–thyroid (HPT) axes [5, 6]. Dysregulation of glucocorticoid, testosterone, and thyroid hormones may contribute to mitochondrial dysfunction, a common underlying factor in both CKD and OSA [7–9].
Mitochondrial dysfunction in the kidneys, a high-energy-demand organ, is particularly detrimental. The kidneys rely heavily on ATP generated by mitochondria to sustain active transport processes critical for reabsorption and excretion. Impaired mitochondrial function disrupts renal energy metabolism, exacerbating renal function decline [10].
Azegami et al. [1] have provided important evidence linking CKD and OSA. However, we propose a bidirectional model where OSA exacerbates CKD progression via pathways involving nocturia, circadian rhythm disruption, and mitochondrial dysfunction. We recommend future studies explore targeted interventions, such as CPAP therapy and pharmacological approaches, to further elucidate and mitigate these interactions. Understanding this complex interplay requires a multidisciplinary approach that integrates nephrology, sleep medicine, and endocrinology. We hope this discussion contributes to the ongoing exploration of CKD and OSA and fosters new avenues for research and clinical interventions.
Author Contributions
Yu-Hsiang Lin: Conceptualization, Writing—Original Draft, Writing—Review & Editing. Kuo-Jen Lin: Conceptualization. Jau-Yuan Chen: Conceptualization.
Disclosure Statements
Financial disclosure: none. Nonfinancial disclosure: none.
Funding
None declared.
Data Sharing Statement
This Letter to the Editor is based on previously published literature and does not involve any new data collected by the authors. All analyses and discussions are derived from publicly available sources, which are cited within the manuscript. Therefore, there are no data sets generated or analyzed during the current study.
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