Original Article Urinary protein expression patterns in children with sleep-disordered breathing: Preliminary findings Jyoti Krishna a,1 , Zahoor A. Shah a,1 , Michael Merchant b , Jon B. Klein b , David Gozal a, * a Division of Pediatric Sleep Medicine and Kosair Children’s Hospital Research Institute, Department of Pediatrics, University of Louisville School of Medicine, 571 S. Preston Street, Suite 321, Louisville, KY 40202, USA b Proteomics Core Laboratory and Kidney Disease Program, Department of Medicine, University of Louisville, Louisville, KY 40202, USA Received 15 August 2005; received in revised form 6 September 2005; accepted 20 September 2005 Abstract Background: Obstructive sleep apnea (OSA) is the most common form of sleep-disordered breathing, with almost 15 million Americans affected and many more at risk. Current diagnostic approach to OSA requires polysomnography, which is laborious, onerous, and time- consuming. There is ample evidence that inflammatory responses to the perturbations associated with OSA trigger a variety of genes and signaling cascades that ultimately lead to end-organ injury and changes in kidney function and protein expression. The aim of this study was therefore to analyze proteins in human urine and assess whether differential expression of particular proteins is associated with the presence of OSA. Methods: Eleven OSA and 11 control children between the ages of three and 14 (malesZ17; femalesZ5) underwent overnight sleep studies followed by a first-morning urine sample. Proteomic analysis of urine samples yielded a unique map of proteins, of which, five spots were selected for further analysis due to their significant intensity differences between OSA and control groups. Results: Mass spectrometry followed by peptide mass fingerprinting conclusively identified four of the five spots as gelsolin, perlecan (a heparan sulfate proteoglycan), albumin, and immunoglobulin (P!0.05 and protein scoresO67). Conclusions: Overall, increased expression of gelsolin and perlecan in the urinary proteome of children with OSA suggests that the episodic hypoxia associated with OSA may lead to changes in protein permeability or alternatively to increased catabolism of these proteins and their excretion in urine. q 2005 Elsevier B.V. All rights reserved. 1. Introduction Obstructive sleep apnea (OSA) is a frequent condition affecting up to 3% of all children and is associated with substantial neurobehavioral and cardiovascular morbidities [1–3]. In America alone, it is estimated that more than two million children suffer from OSA. However, many more children (estimated at 11–12% of all children ages 2–12) snore habitually and are therefore at risk for OSA. To differentiate between primary snoring and OSA, overnight polysomnography is required, which is both time-consuming, labor intensive, expensive, and relatively inconvenient to the child and his or her family. Pediatric patients with sleep-disordered breathing (SDB) are at risk for cardiovascular morbidity, particularly hypertension and left ventricular hypertrophy. Experiments using rodent models of SDB have further revealed that the episodic hypoxia and sleep fragmentation that characterize SDB induce broad inflammatory responses and trigger a variety of genes and signaling cascades, ultimately leading to end-organ injury [4,5]. The close association between inflammation (defined here in its broadest sense) and end- organ injury in the context of SDB further suggests that the magnitude of the inflammatory response may be a major determinant of morbidity. We have recently reported that the hypertension of OSA is also linked to changes in kidney function and protein expression in a rodent model [6], suggesting that urinary proteins may reveal specific alterations induced by the Sleep Medicine 7 (2006) 221–227 www.elsevier.com/locate/sleep 1389-9457/$ - see front matter q 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.sleep.2005.09.010 * Corresponding author. Tel.: C1 502 852 2323; fax: C1 502 852 2215. E-mail address: david.gozal@louisville.edu (D. Gozal). 1 These authors contributed equally to the work.