Purpose Obstructive sleep apnea (OSA) increases the risk of chronic kidney disease (CKD) through exposure to nocturnal hypoxemia. Elevated urine Kidney Injury Molecule-1 (KIM-1) can reflect kidney injury before conventional measures of CKD [estimated glomerular filtration rate (eGFR) and urine albumin: creatinine ratio (ACR)] become abnormal. We investigated if urine KIM-1 is elevated in patients with OSA and if this is associated with an increased estimated risk of CKD progression. Methods Adults (n = 1271) completed diagnostic OSA testing and quantification of eGFR, ACR and KIM-1. OSA severity and nocturnal hypoxemia were quantified using the oxygen desaturation index (ODI, 4%), mean oxygen saturation (SpO2), and the duration of SpO2 < 90% (T90). Mean KIM-1 concentrations were compared between patients with no/mild (ODI < 15), moderate (15 ≤ ODI ≤ 30) and severe OSA (ODI > 30) and the associations between urine KIM-1 and nocturnal hypoxemia with the estimated risk of CKD progression were assessed. Results In the entire cohort, participants with severe OSA (n = 411) had higher KIM-1 than the no/mild (n = 545) and moderate OSA (n = 315) groups (all comparisons, p ≤ 0.047). KIM-1 was positively associated (standardized β; 95% CI) with ODI (0.11; 0.05–0.17) and T90 (0.12; 0.06–0.18) and negatively associated with mean SpO2 (-0.14; -0.21- -0.08). Similar relationships were found in a sub-group of participants (n = 976) with normal eGFR and ACR. Higher KIM-1 was also associated with an increased estimated risk of CKD progression. Conclusion OSA-related hypoxemia is associated with increased urine KIM-1, reflecting kidney injury, both after and, more importantly, before eGFR and ACR become abnormal. Furthermore, elevated KIM-1 is associated with an increased estimated risk of CKD progression. Brief summary <OrderedList> <ListItem> <ItemNumber>1.</ItemNumber> <ItemContent> Current knowledge/study rationale: The association between obstructive sleep apnea (OSA) and chronic kidney disease (CKD) is based on conventional measures of kidney function [estimated glomerular filtration rate (eGFR) and albumin: creatinine ratio (ACR)] which are relatively late indicators of kidney damage. Kidney Injury Molecule-1 (KIM-1) is a sensitive urine biomarker that reflects early kidney injury. </ItemContent> </ListItem> <ListItem> <ItemNumber>2.</ItemNumber> <ItemContent> Study impact: We found that urine KIM-1 is increased in patients with severe OSA both before and after eGFR and ACR become abnormal, and that elevated KIM-1 is associated with increased estimated risk of CKD progression. These findings highlight that OSA likely contributes to kidney injury before it becomes clinically or biochemically apparent and sensitive biomarkers, like KIM-1, may help identify patients at increased estimated risk of CKD progression. </ItemContent> </ListItem> </OrderedList>

Nocturnal hypoxemia is associated with increased urine Kidney Injury Molecule-1 (KIM-1) in patients with obstructive sleep apnea

期刊论文
发表日期：

2025年12月29日

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Andrew E. Beaudin,
Jill K. Raneri,
Sofia B. Ahmed,
AJ Marcus Hirsch Allen,
Andrhea Nocon,
Teresa Gomes,
Simon Gakwaya,
Frédéric Sériès,
R. John Kimoff,
Robert P. Skomro,
Najib T. Ayas,
Patrick J. Hanly

摘要

Purpose

Obstructive sleep apnea (OSA) increases the risk of chronic kidney disease (CKD) through exposure to nocturnal hypoxemia. Elevated urine Kidney Injury Molecule-1 (KIM-1) can reflect kidney injury before conventional measures of CKD [estimated glomerular filtration rate (eGFR) and urine albumin: creatinine ratio (ACR)] become abnormal. We investigated if urine KIM-1 is elevated in patients with OSA and if this is associated with an increased estimated risk of CKD progression.

Methods

Adults (n = 1271) completed diagnostic OSA testing and quantification of eGFR, ACR and KIM-1. OSA severity and nocturnal hypoxemia were quantified using the oxygen desaturation index (ODI, 4%), mean oxygen saturation (SpO₂), and the duration of SpO₂ < 90% (T90). Mean KIM-1 concentrations were compared between patients with no/mild (ODI < 15), moderate (15 ≤ ODI ≤ 30) and severe OSA (ODI > 30) and the associations between urine KIM-1 and nocturnal hypoxemia with the estimated risk of CKD progression were assessed.

Results

In the entire cohort, participants with severe OSA (n = 411) had higher KIM-1 than the no/mild (n = 545) and moderate OSA (n = 315) groups (all comparisons, p ≤ 0.047). KIM-1 was positively associated (standardized β; 95% CI) with ODI (0.11; 0.05–0.17) and T90 (0.12; 0.06–0.18) and negatively associated with mean SpO₂ (-0.14; -0.21- -0.08). Similar relationships were found in a sub-group of participants (n = 976) with normal eGFR and ACR. Higher KIM-1 was also associated with an increased estimated risk of CKD progression.

Conclusion

OSA-related hypoxemia is associated with increased urine KIM-1, reflecting kidney injury, both after and, more importantly, before eGFR and ACR become abnormal. Furthermore, elevated KIM-1 is associated with an increased estimated risk of CKD progression.

Brief summary

Current knowledge/study rationale:

The association between obstructive sleep apnea (OSA) and chronic kidney disease (CKD) is based on conventional measures of kidney function [estimated glomerular filtration rate (eGFR) and albumin: creatinine ratio (ACR)] which are relatively late indicators of kidney damage. Kidney Injury Molecule-1 (KIM-1) is a sensitive urine biomarker that reflects early kidney injury.

Study impact:

We found that urine KIM-1 is increased in patients with severe OSA both before and after eGFR and ACR become abnormal, and that elevated KIM-1 is associated with increased estimated risk of CKD progression. These findings highlight that OSA likely contributes to kidney injury before it becomes clinically or biochemically apparent and sensitive biomarkers, like KIM-1, may help identify patients at increased estimated risk of CKD progression.