Sleep Apnea Tied to Early Kidney Stress Even Without Chronic Kidney Disease

Obstructive sleep apnea (OSA) may contribute to early kidney injury, even among adults with no diagnosed chronic kidney disease (CKD), according to a new meta-analysis of 26 studies involving 4302 participants.¹ The findings, published in Sleep Medicine, suggest that OSA is associated with elevations in multiple biomarkers of subclinical renal damage and that the severity of sleep apnea may directly influence the degree of kidney stress.

An estimated 936 million adults aged 30 to 69 years are affected by OSA globally,² and only 8% of high-risk individuals in a 2018 survey had been tested for OSA.³ The condition is increasingly recognized as a potential contributor to early renal injury.¹ However, the authors noted that the effect on kidney function from OSA in individuals without known kidney disease remains uncertain.

They conducted a comprehensive search of PubMed, Embase, MEDLINE, Web of Science, Scopus, and the Cochrane Library through July 7, 2025. Of 2123 records initially identified, 26 studies met inclusion criteria after screening and full-text review. Eligible studies included adults without known CKD who reported at least one biomarker of early renal injury. Standardized mean differences (SMDs) and 95% CIs were pooled, and correlation coefficients were converted to Fisher z-scores.

Across the included studies, 6 primary biomarkers were quantitatively analyzed: urinary microalbumin (UmAlb), cystatin C (CysC), urine albumin-to-creatinine ratio (uACR), neutrophil gelatinase–associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and IL-18. Two additional markers, β2-microglobulin (β2-MG) and liver-type fatty acid–binding protein (L-FABP), were described qualitatively due to limited data.

Compared with non-OSA controls, patients with OSA had significantly higher levels of several biomarkers linked to glomerular dysfunction, tubular injury, and inflammation. UmAlb levels were significantly elevated (SMD = 0.79; 95% CI, 0.18-1.41), although heterogeneity was high. CysC, evaluated in 11 studies, was also significantly increased (SMD = 0.47; 95% CI, 0.34-0.60; P < .001). Similarly, uACR levels were higher in individuals with OSA (SMD = 0.49; 95% CI, 0.15-0.82). NGAL levels were modestly but significantly elevated (SMD = 0.36; 95% CI, 0.12-0.60), while IL-18 showed a particularly large pooled effect size (SMD = 2.27; 95% CI, 0.93-3.60). In contrast, KIM-1 did not differ significantly between OSA and non-OSA groups.

Subgroup analyses revealed a clear dose-response pattern. Biomarker elevations generally intensified with increasing OSA severity. For example, CysC levels rose progressively from mild (SMD = 0.25) to moderate (SMD = 0.41) to severe OSA (SMD = 1.01). UmAlb and uACR showed significant increases primarily in moderate and severe OSA, while NGAL and IL-18 were markedly elevated in severe disease but not consistently in mild cases. These findings suggest that more severe nocturnal hypoxia may exert greater renal stress.

Hypertension emerged as an important effect modifier. In hypertensive populations, OSA was significantly associated with higher UmAlb (SMD = 0.23) and uACR (SMD = 0.61), with more consistent results and lower heterogeneity in some analyses. In normotensive subgroups, associations were not statistically significant. Meta-regression further identified hypertension and smaller sample size as significant contributors to effect size variability, whereas age, body mass index (BMI), ethnicity, and diabetes were not independently associated with effect size.

Polysomnography parameters also correlated with biomarker levels. The apnea-hypopnea index (AHI) was positively associated with CysC, uACR, NGAL, and IL-18. CysC was significantly correlated with markers of nocturnal hypoxia, including oxygen desaturation index and time spent with oxygen saturation below 90%, and inversely correlated with minimum and average oxygen saturation. Higher BMI and poor blood pressure control were independently linked to microalbuminuria, and older age was associated with elevated CysC.

The authors acknowledged that most included studies were cross-sectional, limiting causal inference, and that unadjusted pooled estimates may reflect residual confounding. Nonetheless, the results suggest that OSA is associated with early markers of kidney injury even in the absence of overt nephropathy. Readily available markers such as CysC and UmAlb may help identify high-risk patients, particularly those with severe OSA or hypertension, who could benefit from closer renal monitoring and earlier intervention.

References

1. Xia M, Liu T, Chang F, Salanitro M, Wessel N, Penzel T. Impact of obstructive sleep apnea on early renal injury biomarkers: a systematic review and meta-analysis. Sleep Med. 2026;138:108688. doi:10.1016/j.sleep.2025.108688
2. Benjafield AV, Ayas NT, Eastwood PR, et al. Estimation of the global prevalence and burden of obstructive sleep apnoea: a literature-based analysis. Lancet Respir Med. 2019;7(8):687-698. doi:10.1016/S2213-2600(19)30198-5
3. Braley TJ, Dunietz GL, Chervin RD, Lisabeth LD, Skolarus LE, Burke JF. Recognition and diagnosis of obstructive sleep apnea in older Americans. J Am Geriatr Soc. 2018;66(7):1296-1302. doi: 10.1111/jgs.15372