Original ArticleHigh risk of obstructive sleep apnea is a risk factor of death censored graft loss in kidney transplant recipients: An observational cohort study
Introduction
Obstructive sleep apnea (OSA) is characterized by intermittent hypoxia and fragmented, shallow sleep often followed by excessive daytime sleepiness, fatigue, morning headache and impaired daytime functioning [1]. OSA is a well-established risk factor of hypertension, stroke and cardiovascular (CV) events in the general population [2], [3], [4], [5], [6], [7]. Epidemiologic data also suggest that the prevalence of adverse CV conditions associated with loud snoring and sleep disordered breathing (SDB) may be different in women versus men [8].
Several studies showed an increased prevalence of SDB among patients with different stages of chronic kidney disease (CKD) [9], [10], [11], [12]. Nocturnal hypoxemia predicted CV events among dialyzed patients [13]. OSA was also associated with the Framingham coronary risk score in kidney transplant recipients (TX) [14].
Despite the potential clinical relevance, OSA has only rarely been investigated among TX patients. We recently reported that the prevalence of high risk for obstructive sleep apnea (HRO) was 27% in a sample of 841 unselected TX patients, similar to that seen in dialyzed patients [15]. Subsequently we confirmed these findings using overnight polysomnography [14]. High prevalence of OSA among TX patients was also found in two recent studies [16], [17], although others reported that the prevalence was similar to what was observed in control individuals [18].
The association between OSA and hypertension, accelerated atherosclerosis and vascular damage was confirmed in patients with chronic kidney disease (CKD) [19], [20]. The complex pathomechanism that links OSA to CV risk may also have a detrimental effect on renal function. Indeed, Kinebuchi et al. documented glomerular hyperfiltration in patients with OSA, which was alleviated by short-term continuous positive airway pressure (CPAP) treatment suggesting that OSA may be a risk factor of progressive renal dysfunction [21].
Based on these data we hypothesized that OSA may contribute to graft loss and mortality following renal transplantation. We therefore assessed if high risk of OSA as measured with the Berlin Questionnaire is an independent predictor of death censored graft loss or mortality in kidney transplant patients. The potential interaction between gender and OSA was also considered.
Section snippets
Patient sample and data collection
All stable kidney transplant recipients 18 years of age or older (n = 1067) who were regularly followed at a single kidney transplant outpatient clinic at the Department of Transplantation and Surgery at Semmelweis University, Budapest, were invited to participate in this prospective prevalent cohort study. The baseline assessment was conducted between August 2002 and February 2003 (Transplantation and Quality of Life-Hungary Study [TransQoL-HU Study]) [15], [22], [23], [24].
Demographic data and
Demographics and baseline characteristics
Of the 1067 eligible patients, 108 (10%) refused to participate in the study and 118 (11%) did not complete the Berlin questionnaire. Of the remaining patients 18 (1.6%) were lost to follow up. The study population therefore included 823 patients. There were no significant differences in demographic characteristics and clinical parameters between those who did not complete the Berlin questionnaire or were lost during the follow-up vs. the participating group (data not shown).
Baseline
Discussion
This is the first longitudinal study to show that HRO is an independent risk factor of graft loss in female kidney transplant recipients. Mortality was higher in male TX patients with HRO, but this association was not significant any more after age was introduced into the model.
Several studies reported a strong association between CKD and OSA [9], [10], [11], [12]. The association between OSA and CKD is probably bidirectional. Potential consequences of sleep apnea, such as increased renal
Conflict of Interest
None to declare.
Acknowledgements
The authors thank the patients and the staff in the Department of Transplantation and Surgery, Semmelweis University Budapest. This study was supported by grants from the National Research Fund (OTKA) (F-68841; HUMAN-MB08-A-81231), ETT (206/09), the Hungarian Kidney Foundation, Hungarian Society of Hypertension, Hungarian Society of Nephrology and the Foundation for Prevention in Medicine. This paper was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences
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These authors contributed to the paper equally.