In this study, the proportions of patients with sleep disorders and SAS among 30 ESRD patients were 93.3% and 83.3% respectively, which were higher than those of previous studies (50-70%).2,3
Parker et al.2
showed that 23 among 46 HD patients (50%) had an AHI above 5, a result that seems to differ from ours, for they excluded those subjects with SAS, PLMS, or RLS by means of a structured interview. Kimmel et al.3
reported that the proportion of OSAHS patients among those ESRD patients with SAS was 56% (9/16), which is lower than 72% (18/25) in the present study: 60% of our ESRD patients were diagnosed with PLMS. It has been reported that the incidence of PLMS in ESRD patients is 30-70% in general.2,4
In our study, it is notable that 19 patients (50%) had diagnoses of both SAS and PLMS. Previous studies have reported either SAS or PLMS separately, except for the study of Parker et al.2
where 12 (26%) of 46 ESRD patients had both an AHI and LMI greater than 5. In our study, 5 (31%) of 16 ESRD patients who completed the SDQ complained of RLS symptoms. In previous studies, RLS has been variously reported as affecting 7-60% of ESRD patients. Rijsman et al.16
reported that 58.3% of ESRD patients had RLS, and PLMS was found in 90% of those with RLS. The RLS with PLMS seems to be clinically important in ESRD patients, since it worsens the quality of life.16
Increased UA was related to increased total sleep time (TST) and to decreased AHI and ODI in our study. Hsu et al.21
recently suggested a positive effect of UA related to its antioxidant properties, predicting higher mortality in HD patients with lower UA levels. However, UA increases in oxidative stress situations such as hypertension, cardiovascular disease, and obstructive sleep apnea (OSA).17-20
So, it remains controversial whether serum UA actually has antioxidant properties.
and ESRD have been considered as oxidative stress disorders.6
Although the mechanism related to increased oxidative stress could be explained by various factors in ESRD patients, the major cause would be the retention of oxidized solute by the loss of renal function. Supporting our result that increased UA was related to an improvement in SBD, UA has been suggested to have antioxidant properties in several studies. Hasegawa et al.9
suggested that UA plays an important role as an antioxidant in ESRD patients, and Christou et al.22
reported that UA's antioxidant capacity was significantly decreased in OSA patients with an AHI of more than 20. Our previous study also found that increased ODI in SAS was related to decreased total antioxidant status (TAS) level, reflecting the antioxidant capacity in ESRD patients.23
In ESRD patients, the association of OSA with a deficit of antioxidant capacity may imply that the oxidative stress reaction is increased due to the reduced level of cellular reductants under a hypoxemic state such as OSA, or the reduced antioxidant capacity results in the occurrence or aggravation of OSA. Our study showed that UA levels were significantly correlated with the nPCR (r=0.492), reflecting the nutritional state of proteins. Söreide et al.8
reported that the intake of branch-chain amino acids (BCAAs) in ESRD patients was associated with respiratory stimulation during sleep. Malnutrition would also be associated with increased oxidative stress, thus explaining the mechanism underlying the relationship between protein nutrition and respiration during sleep, although this explanation is not conclusive.24
Therefore, the improvement of SBD may be due to the antioxidant properties of UA, reflecting protein nutrition.
As the CRP level increased, the LMI increased in our study, and there was no sleep parameter correlated with IL-6. In ESRD patients, although it was reported that sleepiness was induced by the abnormal production of TNF, a substance with somnogenic properties,25
the relationship of the sleep variables with inflammatory markers such as CRP and IL-6 has not yet been studied. ESRD is recognized as a chronic inflammatory disease, because these inflammatory markers are higher in ESRD patients.6
On the other hand, it is known that the metabolic abnormality of dopamine can cause an inflammatory reaction,26
and impaired dopaminergic neurotransmission is a major factor in the pathogenesis of RLS,27
which is often accompanied by increased limb movement (LM) during sleep. Accordingly, increased CRP would have been correlated with increased LM. However, IL-6, another inflammatory marker, was not correlated with LM in our study. This could be explained by the instability of the measurement of IL-6, since IL-6 was not detected in 7 patients, and the IL-6 data were measured only once. Therefore, the relationship between inflammatory markers and LM in ESRD patients cannot be definitively determined from our results, and further studies will be necessary.
The limitations of our study are as follows. First, comorbid medical diseases such as hypertension and diabetes mellitus were not excluded, since these are relatively common in ESRD patients. Since it was also very difficult to exclude patients taking some form of medication (except hypnotics), these substances may have affected nocturnal sleep in our study. Second, our results are not conclusive, since confounding variables such as age, sex and BMI, which affect AHI and LMI, were not controlled. Third, we did not conduct multiple sleep studies to reduce the first-night effect and ESRD patients with possible primary sleep disorders were not excluded from our study, resulting in the presence of extreme values of the nocturnal sleep variables.
However, a limited number of studies on the relationship between sleep disorder and metabolic markers in ESRD patients have been reported. In Asian countries, there has only been one study using the sleep questionnaire without conducting NPSG. Considering the recent findings that ESRD is recognized as an oxidative stress disease or an inflammatory disease, it is meaningful that UA was significantly related to decreased severity of SBD, and CRP was related to increased severity of LM in our study. These findings suggest that UA or CRP levels reflect certain sleep disorders in ESRD patients. Further studies on the relationship of these markers to the pathophysiology of sleep disorders are necessary.