Department of Medicine, University of Calgary, Calgary, AB, Canada.
Sleep Centre, Foothills Medical Centre, Calgary, AB, Canada.
Physiol Rep. 2020 Mar;8(6):e14376. doi: 10.14814/phy2.14376.
Obstructive sleep apnea (OSA) may contribute to kidney injury by activation of the renin-angiotensin system (RAS), which is reduced by continuous positive airway pressure (CPAP) therapy. A biomarker in the urine that reflects renal RAS activity could identify patients at risk of kidney injury and monitor their response to CPAP therapy. Nine patients with OSA and six matched control subjects without OSA were recruited. Renal RAS activity was measured by the renovasoconstrictor response to Angiotensin II challenge, a validated marker of RAS activity, and urine samples were collected in all subjects at baseline and repeated in those with OSA following treatment with CPAP. A broad range (1,310) of urine analytes was measured including 26 associated with the RAS signaling pathway. The OSA group was a similar age and weight as the control group (48.7 ± 10.4 vs. 47.7 ± 9.3 yrs; BMI 36.9 ± 7.2 vs. 34.7 ± 2.5 kg/m ) and had severe sleep apnea (ODI 51.1 ± 26.8 vs. 4.3 ± 2/hour) and nocturnal hypoxemia (mean SaO 87 ± 5.2 vs. 92.6 ± 1.1%). CPAP corrected OSA associated with a return of the renovasocontrictor response to Angiotensin II to control levels. Partial least squares (PLS) logistic regression analysis showed significant separation between pre- and post-CPAP levels (p < .002) when all analytes were used, and a strong trend when only RAS-associated analytes were used (p = .05). These findings support the concept that urine analytes may be used to identify OSA patients who are susceptible to kidney injury from OSA before renal function deteriorates and to monitor the impact of CPAP therapy on renal RAS activity.
阻塞性睡眠呼吸暂停（OSA）可通过肾素-血管紧张素系统（RAS）的激活导致肾脏损伤，而持续气道正压通气（CPAP）治疗可降低 RAS。尿液中的生物标志物可反映肾脏 RAS 活性，有助于识别易发生 OSA 相关肾脏损伤的患者，并监测 CPAP 治疗对其的影响。本研究纳入了 9 名 OSA 患者和 6 名匹配的无 OSA 对照者。通过血管紧张素 II 刺激试验评估肾血管收缩反应，这是 RAS 活性的验证性标志物，来测量肾脏 RAS 活性，所有受试者在基线时采集尿液样本，在 OSA 患者接受 CPAP 治疗后重复采集。共检测了包括 26 种与 RAS 信号通路相关的尿液分析物，其范围很广（1310 种）。OSA 组的年龄和体重与对照组相似（48.7 ± 10.4 比 47.7 ± 9.3 岁；BMI 36.9 ± 7.2 比 34.7 ± 2.5 kg/m ），且患有严重的睡眠呼吸暂停（ODI 51.1 ± 26.8 比 4.3 ± 2 小时/小时）和夜间低氧血症（平均 SaO 87 ± 5.2 比 92.6 ± 1.1%）。CPAP 纠正 OSA 可使血管紧张素 II 引起的肾血管收缩反应恢复至对照水平。当使用所有分析物时，偏最小二乘（PLS）逻辑回归分析显示 CPAP 治疗前后的水平存在显著差异（p <.002），而当仅使用与 RAS 相关的分析物时，这种差异呈强烈趋势（p =.05）。这些发现支持这样一种观点，即尿液分析物可用于识别在肾功能恶化之前易发生 OSA 相关肾脏损伤的 OSA 患者，并监测 CPAP 治疗对肾脏 RAS 活性的影响。
