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

purposeObstructive 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.

methodsAdults (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.

resultsIn 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.

conclusionOSA-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. 1. 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. 2. 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.