Abstract
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/m2) and had severe sleep apnea (ODI 51.1 ± 26.8 vs. 4.3 ± 2/hour) and nocturnal hypoxemia (mean SaO2 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.
Highlights
We have shown in patients with Obstructive sleep apnea (OSA), who had normal kidney function, that nocturnal hypoxemia increases renin–angiotensin system (RAS) activity in the kidney (Zalucky et al, 2015) and that this is corrected by treatment with continuous positive airway pressure (CPAP) (Nicholl et al, 2014)
In this study of human subjects with OSA, we have shown that a broad range of urine analytes change significantly when nocturnal hypoxemia due to OSA is corrected by CPAP therapy
There is a strong trend for a similar change in a smaller number of urine analytes involved in the RAS pathway following CPAP, which may reflect the associated downregulation of renal RAS in these patients
Summary
Some patients may benefit from higher doses of these medications, independent of BP effects (Miller et al, 2006), but some still progress to end-stage kidney disease (ESKD) despite maximal therapy. This highlights the need both to identify RAS activity at the point of care and to seek additional therapeutic options for RAS inhibition. We have shown in patients with OSA, who had normal kidney function, that nocturnal hypoxemia increases RAS activity in the kidney (Zalucky et al, 2015) and that this is corrected by treatment with continuous positive airway pressure (CPAP) (Nicholl et al, 2014)
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