Obstructive sleep apnea (OSA) affects approximately 34% of middle-aged men and 17% of women, representing a major public health concern (1). This highly prevalent disorder is characterized by recurrent episodes of upper airway obstruction during sleep, leading to intermittent hypoxia, sleep fragmentation, and sympathetic activation (2, 3). These pathophysiological disturbances contribute to a wide range of adverse health outcomes, including hypertension, arrhythmia, coronary artery disease, stroke, insulin resistance, and dyslipidemia (4–7). Beyond its well-established effects on cardiovascular health, emerging evidence links OSA to progressive kidney disease through mechanisms such as chronic intermittent hypoxia, sympathetic activation, and systemic inflammation (8–11). Population-based studies have demonstrated that patients with OSA face an increased risk of incident chronic kidney disease (CKD) and accelerated decline in renal function independent of traditional risk factors such as hypertension and diabetes mellitus (12–15).

Iron deficiency anemia (IDA) is among the most common nutritional disorders globally and disproportionately affects women owing to menstruation, pregnancy, and dietary factors (16). Disruptions in iron homeostasis can contribute to renal injury through mitochondrial dysfunction, oxidative stress, and endothelial impairment (17, 18). Experimental studies further demonstrated that iron deficiency amplifies kidney damage by enhancing oxidative injury and ferroptosis, thereby accelerating tubular and vascular injury (19). Clinically, reduced hemoglobin levels or anemia have been identified as independent predictors of rapid renal function decline in patients with type 2 diabetes, underscoring the importance of adequate oxygen delivery and mitochondrial efficiency for kidney health (20, 21). Despite this growing evidence, most investigations have focused on the general or diabetic population, while limited research has explored these associations in individuals with OSA. Given that OSA induces chronic intermittent hypoxia, sympathetic activation, and systemic inflammation, the coexistence of IDA may synergistically worsen renal vulnerability by overlapping the hypoxic and oxidative pathways. Accordingly, this study aimed to examine the association between IDA and renal function decline in a large, multi-institutional cohort of adults with a first diagnosis of OSA.

This multi-institutional cohort study demonstrated a significant association between IDA and adverse renal outcomes in adults with OSA. After propensity score matching of 38,064 paired patients, IDA was associated with a 23% higher cumulative incidence of composite renal function decline at both 5-year and 7-year follow-ups. These associations persisted across multiple sensitivity analyses and remained consistent in patients with preserved baseline renal function. Secondary outcomes, including AKI, pulmonary hypertension, all-cause mortality, and ICU admission, were all significantly associated with IDA. Subgroup analyses revealed uniform associations across demographic and clinical characteristics, with no significant effect modification detected by sex, age, hypertension status, obesity, cardiovascular disease, or diabetes mellitus.

Current evidence has consistently demonstrated that OSA is linked to an elevated risk of developing CKD. Lee et al. (14) observed a 1.94-fold higher incidence of CKD among patients with sleep apnea. Similarly, a systematic review and meta-analysis encompassing 18 studies reported a pooled odds ratio of 1.77, confirming a robust association between OSA and CKD (25). However, the present study represents the first large-scale investigation to specifically examine the relationship between preexisting IDA and subsequent renal function decline in patients with OSA. In this study, patients with IDA exhibited a 23% higher risk of composite renal function decline, indicating that IDA may be associated with an additional risk of kidney disease progression beyond the known effects of OSA. This finding extends the current understanding by identifying a potentially modifiable nutritional factor that may influence renal outcomes in this vulnerable population. The persistence of these associations in sensitivity analyses strengthens the robustness of these observations and suggests that IDA may be associated with renal injury, even in individuals with preserved baseline kidney function.

The observed association between IDA and AKI in our cohort provides additional evidence linking IDA to renal injury in patients with OSA. Prior studies have established that OSA may predispose individuals to AKI through intermittent hypoxia, sympathetic activation, and endothelial injury. For example, Chuang et al. (26) reported that OSA severity correlated positively with multiple serum markers of AKI, including cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), and interleukin-18, whereas continuous positive airway pressure therapy reduced albuminuria and IL-18 levels. Similarly, Nowicki et al. (27) demonstrated overnight elevations in urinary NGAL and kidney injury molecule-1 following apneic episodes, suggesting subclinical renal injury. Furthermore, Dou et al. (28) identified OSA as an independent risk factor for AKI among critically ill patients. Building on this evidence, the present study extends our understanding by examining the association between pre-existing IDA and subsequent AKI within an OSA population. The finding that IDA in patients with OSA is associated with both chronic renal function decline and AKI strengthens the hypothesis that IDA may be associated with multiple forms of kidney injury in this population. While previous studies have primarily focused on anemia as a predictor of AKI in surgical populations (29–31), the present study demonstrates this association specifically in the OSA population.

Iron deficiency commonly coexists with pulmonary hypertension, with a high prevalence reported across various subtypes of pulmonary hypertension (32). Experimental studies have shown that iron deficiency can promote pulmonary vascular remodeling and elevate pulmonary arterial pressure, suggesting a mechanistic link between disrupted iron homeostasis and the development of pulmonary hypertension (33, 34). However, despite these preclinical findings, clinical evidence directly confirming a causal relationship between iron deficiency and pulmonary hypertension remains limited (35, 36). Our study appears to be the first large-scale analysis to specifically evaluate the association between pre-existing IDA and incident pulmonary hypertension within the OSA population. The clinical importance of this finding is underscored by the serious nature of pulmonary hypertension as a complication. Pulmonary hypertension is characterized by elevated pulmonary artery pressure and progressive pulmonary vascular remodeling, which can lead to right ventricular dysfunction and heart failure if left untreated (37, 38). In patients with OSA who already face increased cardiovascular risks, the development of pulmonary hypertension represents a particularly concerning complication that may substantially impact prognosis. These findings broaden the current understanding of pulmonary vascular disease in OSA and highlight IDA as a potential modifiable risk factor.

These findings have important implications for the management of patients with OSA. IDA may serve as a marker identifying individuals at heightened risk for renal function decline and pulmonary vascular complications, warranting closer monitoring of the kidney and cardiovascular status. The observed associations with both chronic and AKI suggest that evaluation of IDA may be valuable across the continuum of OSA care, including during acute illnesses or perioperative periods. Although the current OSA guidelines rarely address nutritional deficiencies, these results support the incorporation of routine iron assessment into clinical practice. Whether correcting iron deficiency through supplementation or treatment of the underlying causes can improve renal or pulmonary outcomes remains to be determined in future prospective studies. The additional associations between all-cause mortality and ICU admission highlight the broader clinical relevance of IDA and the need for comprehensive risk management in this population.

In the current study, several limitations warrant consideration. First, the retrospective observational design precludes definitive conclusions regarding causality, and residual confounding from unmeasured variables remains possible. Although a broad range of demographic and clinical variables were included in the propensity score matching model, specific autoimmune and systemic inflammatory diseases could not be comprehensively ascertained or modeled in the TriNetX database. Residual confounding related to these immune-mediated conditions, which may influence both anemia and renal outcomes, therefore cannot be excluded. Second, information regarding iron supplementation during follow-up was not systematically captured, potentially attenuating the observed associations if some patients received treatment. Detailed iron parameters, including serum ferritin, transferrin saturation, and markers distinguishing absolute from functional iron deficiency, were not systematically available. Third, both OSA and IDA were identified using ICD-10 diagnostic codes without direct clinical validation; the lack of polysomnography data for OSA and laboratory confirmation of iron indices or hemoglobin levels for IDA introduces a risk of diagnostic misclassification, including miscoding of anemia subtypes and inter-institutional variability in coding practices, which may bias exposure and outcome ascertainment and attenuate the observed associations. In addition, disease severity could not be assessed, as information on OSA severity (e.g., apnea–hypopnea index) and treatment adherence (e.g., continuous positive airway pressure use) was unavailable, precluding evaluation of dose–response relationships despite the known link between OSA severity and renal outcomes. As a result, we were unable to incorporate these factors into adjustment, stratified, or sensitivity analyses, and potential effect modification by OSA severity cannot be excluded. These limitations are inherent to large-scale electronic health record–based studies and highlight the need for prospective investigations incorporating polysomnography, detailed iron parameters, and longitudinal renal biomarkers to validate and extend these findings. Fourth, serial kidney function measurements were not systematically obtained, which precluded detailed trajectory analyses. Finally, mechanistic biomarkers, including inflammatory markers and oxidative stress parameters, were not consistently available.

This study demonstrated significant associations between IDA and increased risk of renal function decline, AKI, and pulmonary hypertension development in patients with OSA. These relationships persist across multiple analytical approaches. Future prospective investigations incorporating serial measurements of iron status, mechanistic biomarkers, and treatment adherence assessment are needed to clarify the temporal relationships. Randomized controlled trials evaluating whether interventions targeting iron deficiency favorably influence renal and pulmonary vascular outcomes in patients with OSA would provide evidence for potential therapeutic strategies.