Sleep quality in renal transplant patients: a never investigated problem
Massimo Sabbatini1,
Anna Crispo2,
Antonio Pisani1,
Riccardo Gallo1,
Bruno Cianciaruso1,
Giorgio Fuiano3,
Stefano Federico1 and
Vittorio E. Andreucci1
1 Division of Nephrology, University Federico II, Naples, Italy, 2 Department of Epidemiology, Fondazione Pascale, Naples, Italy and 3 Division of Nephrology, University of Catanzaro, Italy
Correspondence and offprint requests to: Massimo Sabbatini, MD, PhD, Università Federico II, Via A. Manzoni 50, 80123 Naples, Italy. Email: sabbatin{at}unina.it
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Abstract
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Background. Despite the great prevalence of sleep disorders and the low quality of sleep in patients with renal diseases, to date no study has evaluated these problems in renal transplant patients.
Methods. The aim of the study was to assess sleep quality (SQ) in 301 kidney graft recipients by the Pittsburgh Sleep Quality Index (PSQI, range 021, with higher scores indicating worse SQ), in comparison with PSQI of both patients on haemodialysis (HD) (n = 245) and normal control subjects (n = 169).
Results. PSQI of renal transplant patients averaged 6.46±3.71, a value significantly lower than in HD patients (8.52±3.81, P<0.001), but higher than in control subjects (3.54±1.61, P<0.0001 vs both transplant and dialysis patients). No correlation was found between PSQI and the main biochemical parameters of transplant patients. When the patients were divided into good (PSQI<5) or poor (PSQI>5) sleepers, a significant risk of psychological problems was associated with the condition of poor sleeper (OR: 2.3; P<0.02), with no further correlation detected in either of the two groups.
Conclusions. These data demonstrate that SQ in renal transplant patients is surprisingly low, despite a well preserved renal function, and that poor sleep in these patients is also secondary to psychological problems. The use of PSQI in such patients represents a useful tool for the investigation of SQ and quality of life.
Keywords: renal transplantation; restless legs syndrome; sleep apnea; sleep quality
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Introduction
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Several studies have recently reported the impressive prevalence of sleep disturbances in uraemic patients, both in dialysis and under conservative treatment [14], focusing on how both psychological and organic factors play well defined roles in determining bad quality of sleep. The relevant interest in this topic mostly derives from the clinical association between some disturbances which fragment sleep and the increased risk of cardiovascular events or disturbances in immune function [57], which represent the leading causes of death in patients with renal diseases, including renal transplanted (TX) patients. Surprisingly, to date no clinical study has investigated the quality of sleep in TX patients. Presumably, the better quality of life (QOL) of TX patients compared to haemodialysis (HD) patients [8], and the clinical improvement of some dangerous sleep-related problems, like sleep apnoea (SA) [9] or restless legs syndrome (RLS) [10], may erroneously suggest that sleep problems vanish after a successful transplantation.
Therefore, on the basis of our previous studies, we have assessed the quality of sleep in a large cohort of renal TX patients, in the attempt to find any relationship with their demographic and biochemical data, and to verify whether renal transplantation may substantially improve the sleep-related problems observed in HD patients.
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Subjects and methods
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The quality of sleep was measured in 301 consecutive renal TX out-patients attending our Department during their periodic follow-up through a cross-sectional analysis. All patients were older than 18, and had had a functioning transplanted kidney for at least 6 months. Patients unable to give their informed consent were excluded from the study as were patients with neoplasia or with diagnoses of psychiatric disease (n = 11). Only 17 patients refused to participate in the study because of no interest in it. The immunosuppressive regimen included cyclosporin (n = 236), tacrolimus (n = 53), and mycophenolate or azathioprine (n = 155); 255 patients consumed steroids. Sleep quality was determined by the Pittsburgh Sleep Quality Index (PSQI), a score derived by a self-rated questionnaire, consisting of 19 questions which assess a wide variety of factors related to sleep quality in the previous month; these included estimates of sleep duration and latency, as well as frequency and severity of specific sleep-related problems [11]. The 19 questions are grouped into seven components scores, each weighted equally on a 03 scale. The seven components are then summed to yield a global PSQI score (range: 021): higher scores indicate worse sleep quality. The seven components of the PSQI are: (i) subjective sleep quality, (ii) sleep latency, (iii) sleep duration, (iv) habitual sleep efficiency, (v) sleep disturbances, (vi) use of sleeping medications, and (vii) daytime dysfunction. According to Buysse et al. [11], patients with a PSQI score > 5 are conventionally defined poor sleepers, whereas those with a score
5 are considered good sleepers [11]. Further questions, not included in the Pittsburgh questionnaire, investigated the identification of possible causes of sleep disorders (emotional or organic), as well as the subjective presence of stop-breathing episodes or RLS symptoms, as previously defined [1] (Table 1).
The PSQI of TX patients was compared with the PSQI of 169 normal subjects (NOR), representative of a normal population without known disease, randomly selected by in-person interview among the general population on the basis of their age (mean age of TX patients±5 years), and the PSQI of 245 patients on maintenance HD [4]. HD patients were surveyed during their HD session; patients who had been on dialysis < 6 months or were in critical clinical conditions were excluded [4].
Data were analysed using the Statistical Package for Social Sciences (SPSS) for Windows, version 8.0 software (SPSS Inc., IL, USA). Since the distribution of variables was not known, non-parametric tests were used. The Spearman correlation coefficient was used to examine associations between continuous variables and the PSQI. The prevalence of poor sleepers was then determined by the proportion of subjects with a global PSQI > 5; a multiple logistic regression was then performed in transplanted patients, to evaluate the relationship between some selected variables and the risk of being poor sleepers. The regression equations included terms for age, body mass index (BMI), and time on dialysis and transplantation. A P-value < 0.05 was considered statistically significant. The data are expressed as means±1 SD.
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Results
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The PSQI of normal subjects averaged 3.54±1.61; this value was greatly increased in transplanted patients (6.46±3.71, P<0.0001 vs NOR), even resulting significantly lower than in HD patients (8.52±3.81, P<0.001 vs TX and P<0.0001 vs NOR). Since HD patients were older than TX patients, all HD patients on an active waiting list for transplantation were separated (n = 90) and considered as a further subgroup (HD-WL); despite their age was similar to TX patients (45.6±9.1 vs 44.8±11.5, NS), their PSQI remained significantly higher than in TX patients (7.93±4.17, P<0.001 vs TX); a further difference among the groups was detected in BMI, it being higher in TX patients (P<0.001 vs other groups, ANOVA). The score of the single components of sleep quality in TX patients were all significantly higher than in NOR and lower than in HD patients, with the only exceptions being sleeping pills intake, similar to NOR subjects, and daytime dysfunction, comparable to HD patients. Considering only HD-WL patients, these differences still persisted, with the exception of sleep duration and sleep disturbances, which were similar between TX and HD-WL patients.
With bivariate analysis, a significant correlation was detected between total score of PSQI in TX patients and their age (r = 0.2, P<0.002), but no further relationship existed with cumulative time on dialysis, after transplantation, haemoglobin, C-reactive protein, and calculated creatinine clearance, nor with doses or blood levels of cyclosporin, tacrolimus and steroids (Table 2).
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Table 2. Demographic data of total transplanted patients (TX), and good sleepers and poor sleepers patients (with PSQI < 5, and > 5, respectively)
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The percentages of good and poor sleepers (i.e. patients with a PSQI < 5 and > 5, respectively) were 47.5 and 52.5, respectively; these subgroups only differed in age, it being higher in poor sleepers (P<0.007). Once again, bivariate analysis showed no correlation in the two separate subgroups between PSQI and all the parameters reported in Table 2. In poor sleepers (n = 158), the multivariate logistic regression, corrected by time after transplantation and BMI, could not evidence any risk-factor among all the variables considered in the study.
An interesting finding came from the analysis of the subjective causes negatively influencing the quality of sleep (Table 3). These causes were empirically divided into two categories: psychological (anxiety, fear and depression) and organic (pruritus, digestive symptoms, pain and RLS symptoms). Only 174 patients out of 301 answered these questions, since the remainder reported having good quality sleep; a statistical difference between the two groups was detected in the subjective causes of bad quality of sleep (
2 = 43.94, P<0.001 poor vs good sleepers). In particular, poor sleepers described a great prevalence of emotional disorders accounting for 70.5% of reported causes, with anxiety playing a prominent role (52.4%), while good sleepers reported these factors as responsible for their sleep quality only in 55.7% of cases (anxiety: 44.2%). The multiple regression analysis, adjusted for sex and age, showed a significant risk of psychological problems in poor sleepers (OR = 2.3, 95% CI = 1.24.8, P<0.02, n = 174), whereas there was no additional risk with the organic causes.
Lastly, 52 patients (36 were poor sleepers) complained of subjective problems of stop-breathing episodes, and 114 patients (43 poor sleepers) referred to RLS symptoms, as previously defined [1]; both symptoms, however, occurred with no significant difference between good and poor sleepers.
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Discussion
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These results clearly demonstrate that the quality of sleep of renal transplanted patients is dramatically compromised in the absence of definite relationships with any specific demographic or biochemical parameter, with the exception of age. This conclusion is quite surprising, considering that TX patients certainly benefit from a better QOL than HD patients [8], and that important changes occur in sleep disturbances after transplantation, like the reported disappearance of SA [9] and the recovery from RLS [10]. Moreover, these data demonstrate that a bad sleep quality is not exclusive to HD patients, but the process of dialysis represents an adjunctive disruptive process [12], since HD patients on a waiting list, despite a comaparable age with TX patients, have a worse PSQI.
In their apparent simplicity, these data deserve attention for their possible clinical implications. Evidence is emerging of well defined relationships between some disorders influencing sleep quality, like SA, with cardiovascular consequences (disruption of circadian rhythm, increased hypertensive burden and left ventricular hypertrophy) [5,6], or periodic limb movements with increased mortality in HD patients [12]. Sleep deprivation, on the other hand, even in normal subjects, results in elevated levels of C-reactive protein plasma levels, a stable marker of inflammation that has been shown to be predictive of cardiovascular morbidity [13], following its association with elevated blood pressure and heart rate.
Sleep deprivation has also been implicated as a source of impaired immune function: differently from a previous study showing no effect of sleep on immune function [14], it has been recently demonstrated that even a modest disturbance of sleep produces a reduction of natural immune responses and of T-cell cytokine production [15].
Further clinical considerations can be drawn from our results. Our study suggests that stop-breathing episodes still persist in 18% of our TX patients (69% in poor sleepers): the presence of this disorder in a good percentage of patients allows one to suspect that some of these patients may still be affected by sleep apnea (SA), despite a functioning allograft; no relationship, however, was detected between C-reactive protein levels and these symptoms in both poor and good sleepers. Similarly, RLS is reported to recover after transplantation and to appear again when a kidney fails [10]; however, 37% of our TX patients (38% are poor sleepers) are still affected by RLS symptoms, and both these disturbances are sufficient to fragment their sleep, with any possible consequence. The presence of these non-specific symptoms should alert us and compel us to perform a more complex examination in order to ascertain a correct diagnosis of the disorder [16,17].
The impressive prevalence of psychological factors reported as subjective causes of bad quality of sleep was not unexpected. In a large cohort of renal TX patients, Matas et al. [18] have recently shown that, among many covariates influencing the QOL in renal transplanted patients, emotional and psychological problems had the greatest impact, followed by eye diseases, even a long time after transplantation: in 10 year transplanted patients, the QOL was worse in renal TX patients than in patients with heart or liver transplantation, and the highest differences were detected in their psychological status [19].
Our study did not evaluate the prevalence of co-morbid medical conditions linked to dialysis and further enhanced by transplantation, like hypertension, cardiovascular and bone diseases or diabetes, all negatively influencing sleep. It may be hypothesized, however, that the high PSQI of TX patients could be in part secondary, given the long time spent on dialysis (on average 50 months) and then with the transplant (64 months). On the other hand, HD patients on a waiting list for renal transplantation (HD-WL), who should have the lowest prevalence of these co-morbidities, have average scores of PSQI higher than TX patients: this witnesses that sleep quality is also influenced by conditions different from medical co-morbidities.
The risk of psychological problems in poor sleepers could suggest that emotional factors are involved in determining the quality of sleep, but, unfortunately, our analysis does not allow us to ascertain whether these may worsen sleep quality or, conversely, that poor sleep is mainly responsible for them. Similarly, we did not perform specific questionnaires to assess the exact prevalence of depression, commonly involved in sleep disorders.
The low quality of sleep observed in TX patients, who maintain a preserved renal function, definitely rules out the possibility that the retention of middle molecules or, conversely, the loss of some hypno-inducing endogenous substance by dialysis, may determine sleep disorders in HD patients. Finally, it must be acknowledged that sleep quality could have been influenced by a broad range of negative health behaviours, not captured by our questionnaire, like alcohol and coffee intake or smoking, but potentially associated with decreased sleep efficiency, and that, due to the large number of patients, polysomnography could not be performed.
In conclusion, our study shows that sleep quality in renal transplanted patients is unexpectedly low, and demonstrates that poor sleep is not specific to dialysis but may be secondary to different factors, like co-morbidities linked to renal diseases or psychological factors. The PSQI represents an easy and feasible tool to investigate the quality of sleep and indirectly the QOL of renal transplanted patients, and is a useful initial step before submitting patients to more complex procedures.
Conflict of interest statement. None declared.
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Received for publication: 30. 6.04
Accepted in revised form: 20.10.04