Impact of nephrotic leg edema on OSA: gathering a unifying concept for the pathogenetic role of nocturnal rostral fluid shift

Abstract

RATIONALE: Nocturnal rostral fluid shift has been suggested to be a risk factor for obstructive sleep apnea (OSA) in healthy subjects after lower body positive pressurization and in heart failure subjects. Here, we tested whether this may apply to nephrotic lower limb edema and whether remission of the nephrotic syndrome may reverse OSA. METHODS: In subjects with primary steroid-responsive nephrotic syndrome presenting with bilateral lower limb edema, we examined the prevalence and severity of sleep apnea and related parameters before and after the induction of disease remission. MEASUREMENTS AND MAIN RESULTS: Among 16 nephrotic subjects, 7 (43.7%) had sleep apnea (apnea-hypopnea index [AHI]>5) upon presentation. Overall AHI was 14.8±5.0 and was predominantly obstructive in nature. After steroid-based treatment, there was remission of proteinuria associated with complete disappearance of lower limb edema, significant reduction of body mass index, waist, hip and calf circumferences, and total body water mainly in the extracellular compartment. Polysomnographic analyses, performed 8.3±2.8 months after initial presentation, showed improvement in sleep efficiency (P=0.036), mean nocturnal oxygen saturation (P=0.005), shorter duration with oxygen saturation <95% (P=0.044) and <90% (P=0.02), and reduced desaturation index (P=0.011). AHI reduction was close to statistical significance, particularly when confined to subjects with baseline AHI> 5 (P=0.075). There was subjective improvement in self-reported daytime sleepiness (P=0.03). CONCLUSIONS: Nephrotic lower limb edema is a risk factor for nocturnal hypoxemia and possibly also for OSA. This gathers a unifying concept for the pathogenetic role of nocturnal rostral fluid shift in OSA.