obstructive sleep apnea syndrome ( osas ) affects approximately 2% to 4% of the population in developed countries and is an independent risk factor for hypertension , stroke , and myocardial infarction . continuous positive airway pressure ( cpap ) treatment has been shown to reduce sleepiness and cardiovascular risk and remains the major therapy for osas . the goal of cpap therapy is to reduce the apnea - hypopnea index ( ahi ) to < 5 events per hour during sleep . however , simple and objective indicators to monitor the physiological effects of cpap treatment are needed . albuminuria , as indexed by the urine albumin - to - creatinine ratio ( uacr ) , is a sensitive indicator of endothelial injury and is a cardiovascular risk factor in individuals with diabetes and/or hypertension , and the general population . intermittent hypoxia , a characteristic of osa patients , has been shown to be a stronger indicator of endothelial injury than even persistent hypoxemia . lowering albuminuria is associated with better health outcomes and has become an important goal in treating patients with chronic kidney disease with or without hypertension or diabetes . several studies have already demonstrated increased uacrs in osas patients . however , the effect of cpap treatment on uacr in osas patients has not been reported . the goal of this study was to demonstrate the effects of cpap treatment on uacrs in moderate - to - severe osas patients . the study protocol was approved by the research and ethics committee of the chang gung memorial hospital ( cgmh ) in taiwan ( cgmh irb no every patient gave their informed consent prior to participation in the study . between 2008 and 2012 , all adult patients ( 20 years of age ) who visited 1 of 2 sleep clinics with complaints of snoring and sleepiness were prospectively enrolled in the study . standard in - laboratory overnight polysomnography ( embla n7000 ; medcare , reykjavik , iceland ) was performed in each patient . variables recorded included 4 channels of electroencephalogram ( c3/a2 , c4/a1 , o1/a2 , o2/a1 ) ; bilateral electro - oculograms ; chin , left , and right anterior tibial electromyogram ; electrocardiogram ; airflow as measured by pressure sensors and thermistors ; chest and abdominal wall movement as measured by inductive respiratory plethysmographic bands ; snoring as confirmed by wearing a neck microphone ; and arterial oxygen saturation ( spo2 ) as measured by pulse oximetry . all measurements were collected on a computerized sleep system ( somnologica studio 3.0 ; medcare ) . apnea was defined as the cessation of airflow for at least 10 seconds and hypopnea was defined as an abnormal respiratory event with at least 30% reduction of airflow , as compared to baseline , lasting at least 10 seconds , and with at least 3% oxygen desaturation and/or an arousal . ahi was defined as the number of apnea along with hypopnea events per hour of total sleep time . patients were excluded for following reasons : ( 1 ) if they were previously diagnosed with osas , ( 2 ) had a history of diabetes mellitus ( defined as already under control using medication or a fasting blood glucose 126  mg / dl , or hba1c 6.5% at baseline screening ) , ( 3 ) abnormal renal function ( defined as serum creatinine > 1.4  mg / dl ) , ( 4 ) liver cirrhosis , ( 5 ) chronic obstructive pulmonary disease , ( 6 ) hematologic disease , ( 7 ) autoimmune disease , ( 8) cancer , or ( 9 ) recent infection . patients who were taking angiotensin - converting enzyme inhibitors , angiotensin ii receptor blockers , or diuretics were also excluded . attended cpap titration studies the compliance rate was defined as the number of nights in which cpap was used for 4 hours divided by the total number of follow - up days . morning blood and urine samples were collected from all patients at baseline and 6 months after cpap treatment . independent samples t - test analysis was used to compare measurements between patients with poor versus good cpap compliance . repeat measures analysis of variance was used to analyze baseline and follow - up uacrs within- and between - compliance groups . spearman 's correlation test was used to analyze the correlation between cpap compliance rate and changes in uacr . the effects of sex , age , ahi , oxygen desaturation index , creatinine , body mass index ( bmi ) , baseline uacr , and compliance rate on changes in uacr were analyzed by multivariate stepwise linear regression . all analyses were two - tailed , and a p - value < 0.05 was considered statistically significant . statistical analyses were performed using statistical package for social sciences 15.0 for windows ( spss inc , chicago , il ) . independent samples t - test analysis was used to compare measurements between patients with poor versus good cpap compliance . repeat measures analysis of variance was used to analyze baseline and follow - up uacrs within- and between - compliance groups . spearman 's correlation test was used to analyze the correlation between cpap compliance rate and changes in uacr . the effects of sex , age , ahi , oxygen desaturation index , creatinine , body mass index ( bmi ) , baseline uacr , and compliance rate on changes in uacr were analyzed by multivariate stepwise linear regression . all analyses were two - tailed , and a p - value < 0.05 was considered statistically significant . statistical analyses were performed using statistical package for social sciences 15.0 for windows ( spss inc , chicago , il ) . sixty - eight consecutive adult outpatients , who were diagnosed with osa and agreed to use cpap continuously , were enrolled in the study . eight subjects were excluded for taking angiotensin converting enzyme inhibitors or angiotensin receptor blockade medications during the study ( n = 5 ) or failing to comply with follow - up ( n = 3 ) . no antioxidant , such as ascorbic acid ( vitamin c ) or acetylcysteine , was used in these patients during the study period . ( 53% ) patients with cpap compliance rates higher than 50% were defined as the good compliance group . no significant differences in the demographic data were found between the poor compliance versus good compliance groups ( table 1 ) . in both groups , the blood urea nitrogen levels were < 20  mg / dl and the blood urea nitrogen - to - creatinine ratio were all < 20 . no significant change of body weight was also found in both the groups during the treatment period . the black line shows the simple linear regression between ahi and baseline uacr in moderate - to - severe osas patients . ahi = apnea - hypopnea index ; osa = obstructive sleep apnea , osas = obstructive sleep apnea syndrome , uacr = urine albumin - to - creatinine ratio . demographic data and baseline parameters of osa patients in poor compliance and good compliance groups . compared with baseline , uacr significantly improved after 6 months of cpap treatment in the good compliance group ( baseline vs 6 months of cpap : 32.0    9.5 vs 19.2    6.5  mg / g , respectively , p = 0.007 ) , whereas slight worsening in uacrs was noted in patients with poor compliance to cpap treatment ( baseline vs 6 months of cpap : 16.7    4.4 vs 19.1    6.3  mg / g , respectively , p = 0.39 ) . the changes in uacrs between the 2 groups were also significant ( poor compliance vs good compliance groups : 2.4    2.7 vs 12.8    4.4  mg / g , respectively , t = 2.9 , p = 0.005 ) ( fig . 2 ) . mean and individual uacr before and after cpap treatment in good versus poor cpap compliance groups . each dot indicates an uacr level in an osa ) patient and the black lines indicate the changes in uacr in individual patients before and after cpap treatment . the black bars indicate the mean uacr before and after cpap treatment in each group . cpap = continuous positive airway pressure , osa = obstructive sleep apnea ; uacr = urine albumin - to - creatinine ratio . there was a significant negative correlation between compliance rate and change in uacr ( spearman 's correlation coefficient : 0.38 , p = 0.003 ) ( fig . the black line shows the simple linear regression between compliance rate and change in uacr in moderate - to - severe osas patients treated with cpap . cpap = continuous positive airway pressure , osa = obstructive sleep apnea , osas = obstructive sleep apnea syndrome ; uacr = urine albumin to creatinine ratio . multivariate linear regression models were used to determine the associations between changes in uacr and the patients demographic characteristics ( including sex , age , bmi , ahi , oxygen desaturation index , creatinine , baseline uacr ) , and compliance rates . when considering compliance rate , stepwise linear regression analyses revealed that baseline uacr was the most important independent factor in predicting improvement in uacr whereas bmi also had some influence . based on a stepwise linear regression model , the compliance rate was an additional factor that predicted improvement in uacr ( table 2 ) . our study was designed to evaluate the effect of 6 months of cpap treatment on albuminuria in adults with moderate - to - severe osas . as shown in previous studies , a significant correlation between albuminuria and osa severity however , we also found a significant improvement in uacrs in patients with good cpap compliance and a slight worsening in uacrs was noted in patients with poor compliance to cpap treatment . our study also showed a dose - dependent correlation between cpap compliance rates and improvement in uacr levels . because elevated uacr is present in subjects with osas , even after excluding diabetes , hematological disorders , and other known causes of albuminuria , uacr may provide a complementary physiological index of cpap treatment efficacy . our results also showed that baseline uacr , cpap compliance , and bmi were independent predictors of changes in uacr after cpap treatment in osa patients . the higher the baseline uacr ( i.e. , the larger the difference from normal levels ) , the greater the effect of cpap treatment on uacr . improvement in uacr after weight reduction was also noted while weight gain resulted in worsening uacr . the possible mechanisms underlying obesity - induced deterioration in uacr include obesity - related structural and functional changes such as focal segmental glomerulosclerosis or glomerulomegaly with a progressive increase in renal blood flow and filtration rate in the early phase followed by a progressive reduction in filtration rate , with worsening histological lesions , in the late phase . because adiponectin is shown to have a protective effect against the development of albuminuria in the kidneys , downregulation of adiponectin in obesity patients may also play a role in limiting the improvement in uacr after cpap therapy in osa patients with higher bmi . thus , weight reduction is still needed in obese osa patients to induce a better treatment response . our most important findings were that good cpap compliance was an independent factor in improving albuminuria in osa patients and that there was a dose - dependent correlation between cpap compliance rate and improvement in uacr . osa can induce endothelial injury via intermittent hypoxia , increasing sympathetic activity , and an increasing intrathoracic pressure surge . previous studies have also shown that good cpap compliance was associated with better outcomes in osa patients when compared with poor cpap compliance . similarly , our studies showed that uacr was improved in patients with good cpap compliance , whereas uacr worsened in patients with poor cpap compliance . although cpap treatment was provided , patients were not strictly required to use it every day . several of our patients did not turn on the machine and their compliance rate was 0% . patients who had poor compliance with cpap treatment might potentially take less care of their health status and , therefore , would be at higher risk for a worse outcome . in addition , the relatively small sample size could have resulted in type ii statistical error . our results might be criticized when applying to female population due to most of our subjects were male . both epidemiological and sleep clinic - based studies indicate that sleep apnea syndromes are more common in men than in women , the sex difference in prevalence is more marked within the sleep clinic . in addition to this , no different treatment guideline for albuminuria between male and female was reported . finally , most of our patients did not have profound albuminuria ( uacr  >  30  mg / g ) . studies have shown , however , that subjects with intermediate albuminuria ( 5  mg / g    uacr <  30  mg / g ) were already at an increased risk for hypertension , heart failure , and death from cardiovascular diseases , and the risk was higher with higher levels of albuminuria . our study provides evidence that even intermediate albuminuria ( within a certain range ) could be reversed by cpap therapy . in summary , treating osas with cpap ( for 6 months ) can improve albuminuria and the improvement in albuminuria significantly correlated with cpap compliance rate . our findings suggested that measuring uacr can offer a simple screen to examine compliance to ( and effectiveness of ) cpap therapy . whether the improvement in uacr after cpap treatment in osas patients is concomitant with reductions in other comorbidities requires further investigation .
abstracta positive correlation between albuminuria and severity of obstructive sleep apnea syndrome ( osas ) has been demonstrated , as indexed by urine albumin - to - creatinine ratios ( uacrs ) . however , the effect of continuous positive airway pressure ( cpap ) treatment on albuminuria in osas patients has not been established.sixty subjects , with apnea - hypopnea indices > 15  events per hour and no other diagnoses associated with albuminuria , underwent overnight polysomnography for sleep apnea and were examined for uacr at baseline and after 6 months of cpap therapy . 
 cpap compliance rates were also recorded.significant improvement in uacr was found in osas patients with good compliance to cpap treatment after 6 months of therapy ( baseline vs 6-month follow - up , 32.0    9.5 vs 19.2    6.5  mg / g , respectively , p = 0.007 ) , whereas slight worsening in uacrs was noted in patients with poor compliance to cpap treatment ( baseline vs 6-month follow - up , respectively , 16.7    4.4 vs 19.1    6.3  mg / g , respectively , p = 0.39 ) . 
 change in uacr was significant between poor compliance versus good compliance groups ( 2.4    2.7 vs 12.8    4.4  mg / g , respectively , t = 2.9 , p = 0.005 ) . a significant correlation between improvement in uacr and cpap compliance rates 
 was also noted ( spearman 's correlation coefficient : 0.37 , p = 0.007 ) . 
 baseline uacr , good cpap compliance , and body mass index were independent predictors of changes in uacr.adequate cpap treatment improves albuminuria in osas patients . 
 in addition to monitoring cpap adherence and subjective sleepiness , uacr may offer an objective physiological index of cpap therapeutic effectiveness .