Elsevier

Sleep Medicine

Volume 12, Issue 3, March 2011, Pages 267-273
Sleep Medicine

Original Article
High risk of obstructive sleep apnea is a risk factor of death censored graft loss in kidney transplant recipients: An observational cohort study

https://doi.org/10.1016/j.sleep.2010.08.012Get rights and content

Abstract

Objectives

Obstructive sleep apnea (OSA) is associated with increased risk of cardiovascular morbidity in the general population. The clinical significance of OSA among kidney transplant patients is unknown. Our aim was to investigate the association of “high risk of OSA” with death-censored graft loss and mortality in a large cohort of kidney transplant recipients.

Patients and methods

Using the Berlin questionnaire 1067 prevalent kidney transplant recipients were assessed for risk of OSA. Socio-demographic variables, laboratory parameters and data about graft loss and mortality were obtained from the medical records. Multivariable-adjusted associations of OSA risk with graft loss and with all-cause mortality was assessed in competing-risks regression models.

Results

Of the 823 patients who completed the Berlin questionnaire 28% had high risk of OSA (HRO) at baseline. Patients with HRO were older (52 ± 11 vs. 47 ± 13 years, p < 0.001), had a higher prevalence of diabetes (22 vs. 15%, p = 0.018), worse baseline kidney function (estimated glomerular filtration rate: 46 ± 18 vs. 51 ± 19 ml/min/1.73m2, p = 0.001) and higher BMI (27 ± 5 vs. 24 ± 4 kg/m2, p < 0.001). In multivariate models HRO was an independent predictor of graft loss among females after adjusting for age, comorbidity, hypertension, BMI, kidney function, duration of chronic kidney disease, other laboratory parameters and transplant-related data (HR = 3.05; CI: 1.24–7.51; p = 0.015), while HRO did not predict graft survival among males. HRO at baseline was not independently associated with all-cause mortality in the sample.

Conclusion

High risk of OSA is an independent predictor of graft loss among female kidney transplant patients.

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

References (43)

  • M.Z. Molnar et al.

    Restless Legs Syndrome in patients after renal transplantation

    Am J Kidney Dis

    (2005)
  • C.D. Stehouwer et al.

    Urinary albumin excretion, cardiovascular disease, and endothelial dysfunction in non-insulin-dependent diabetes mellitus

    Lancet

    (1992)
  • R. Pedrinelli et al.

    Microalbuminuria and endothelial dysfunction in essential hypertension

    Lancet

    (1994)
  • J.M. Marin et al.

    Long-term cardiovascular outcomes in men with obstructive sleep apnoea–hypopnoea with or without treatment with continuous positive airway pressure: an observational study

    Lancet

    (2005)
  • L.F. Drager et al.

    Characteristics and predictors of obstructive sleep apnea in patients with systemic hypertension

    Am J Cardiol

    (2010)
  • K.J. Reichmuth et al.

    Association of sleep apnea and type II diabetes: a population-based study

    Am J Respir Crit Care Med

    (2005)
  • H.K. Yaggi et al.

    Obstructive sleep apnea as a risk factor for stroke and death

    N Engl J Med

    (2005)
  • A.B. Newman et al.

    Progression and regression of sleep-disordered breathing with changes in weight: the Sleep Heart Health Study

    Arch Intern Med

    (2005)
  • R. Mehra et al.

    Association of nocturnal arrhythmias with sleep-disordered breathing: the Sleep Heart Health Study

    Am J Respir Crit Care Med

    (2006)
  • A. Dunai et al.

    Cardiovascular disease and health-care utilization in snorers: a population survey

    Sleep

    (2008)
  • U. Kuhlmann et al.

    Sleep-apnea in patients with end-stage renal disease and objective results

    Clin Nephrol

    (2000)
  • Cited by (0)

    1

    These authors contributed to the paper equally.

    View full text