Urine biomarkers of renal renin–angiotensin system activity: Exploratory analysis in humans with and without obstructive sleep apnea

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(2)) and had severe sleep apnea (ODI 51.1 ± 26.8 vs. 4.3 ± 2/hour) and nocturnal hypoxemia (mean SaO(2) 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.