Andras Szentkiralyi

Sleep disorders, depressive symptoms and health-related quality of life—a cross-sectional comparison between kidney transplant recipients and waitlisted patients on maintenance dialysis

BACKGROUND Kidney transplantation is believed to improve health-related quality of life (HRQoL) of patients requiring renal replacement therapy (RRT). Recent studies suggested that the observed difference in HRQoL between kidney transplant recipients (Tx) vs patients treated with dialysis may reflect differences in patient characteristics. We tested if Tx patients have better HRQoL compared to waitlisted (WL) patients treated with dialysis after extensive adjustment for covariables. METHODS Eight hundred and eighty-eight prevalent Tx patients followed at a single outpatient transplant clinic and 187 WL patients treated with maintenance dialysis in nine dialysis centres were enrolled in this observational cross-sectional study. Data about socio-demographic and clinical parameters, self-reported depressive symptoms and the most frequent sleep disorders assessed by self-reported questionnaires were collected at enrollment. HRQoL was assessed by the Kidney Disease Quality of Life Questionnaire. RESULTS Patient characteristics were similar in the Tx vs WL groups: the proportion of males (58 vs 60%), mean ± SD age (49 ± 13 vs 49 ± 12) and proportion of diabetics (17 vs 18%), respectively, were all similar. Tx patients had significantly better HRQoL scores compared to the WL group both in generic (Physical function, General health perceptions, Energy/fatigue, Emotional well-being) and in kidney disease-specific domains (Symptoms/problems, Effect- and Burden of kidney disease and Sleep). In multivariate regression models adjusting for clinical and socio-demographic characteristics, sleep disorders and depressive symptoms, the modality of RRT (WL vs Tx) remained independently associated with three (General health perceptions, Effect- and Burden of kidney disease) out of the eight HRQoL dimensions analysed. CONCLUSIONS Kidney Tx recipients have significantly better HRQoL compared to WL dialysis patients in some, but not all, dimensions of quality of life after accounting for differences in patient characteristics. Utilizing multidimensional disease-specific questionnaires will allow better understanding of treatment, disease and patient-related factors potentially affecting quality of life in patients with chronic medical conditions.

A time sequence analysis of the relationship between cardiovascular risk factors, vascular diseases and restless legs syndrome in the general population

Previous cross‐sectional studies regarding the association of restless legs syndrome (RLS) with cardiovascular morbidity are controversial. Our aim was to evaluate prospectively the relationship of cardiovascular risk factors and vascular diseases with incident RLS in the general population. The results are from two prospective population‐based cohort studies: the Dortmund Health Study (n = 1312, median follow‐up of 2.1 years) and the Study of Health in Pomerania (n = 4308, median follow‐up of 5.0 years). RLS status was assessed twice according to the minimal criteria. Diabetes, hypertension, myocardial infarction and stroke, as well as currently taken medications, were assessed as self‐reports. Body mass index and serum total cholesterol were also measured. The independent risks associated with each outcome were estimated by multivariable logistic regression models adjusted for comorbidities and behavioural factors. Obesity was an independent risk factor of incident RLS in the Dortmund Health Study, and higher body mass index was an independent risk factor in both studies. Diabetes, hypertension and hypercholesterolaemia were independent predictors of incident RLS in the Study of Health in Pomerania. The vascular comorbidity index, defined by the number of concurrent cardiovascular risk factors and vascular diseases, showed a positive association with incident RLS in both studies. RLS at baseline was not a significant predictor of any subsequent cardiovascular risk factors and/or vascular diseases in any of the studies. Cardiovascular risk factors and diseases predict the subsequent development of RLS in the general population. The presence of RLS is not a significant risk factor of cardiovascular morbidity.

Association between restless legs syndrome and depression in patients with chronic kidney disease.

Restless legs syndrome (RLS) is reportedly associated with depression. This association may be mediated by both sleep-dependent and sleep-independent mechanisms. Here we analyze the association between RLS and depressive symptoms in patients with chronic kidney disease (CKD). We also assessed whether the relationship is independent of insomnia. In a cross-sectional study, socio-demographic parameters, laboratory data, and medical history were collected from 788 kidney transplant patients and 161 dialyzed patients. Insomnia, depression, and the presence of RLS symptoms were assessed with standard questionnaires. Patients with probable RLS had a higher prevalence of depressive symptoms than those without RLS (56% vs. 22% with vs. without RLS, respectively; P<.001). Patients presenting RLS symptoms had higher Athens Insomnia Scale (AIS) scores than patients without RLS [median AIS score (interquartile range): 7 (6) vs. 3 (4) with vs. without RLS, respectively; P<.001]. The AIS score correlated with the CES-D score (Spearmans rho=0.54, P<.001). In multivariate analysis, the presence of RLS symptoms was independently associated with depressive symptoms (OR=3.96, 95% CI 2.21-7.1, P<.001). This relationship remained significant even after including insomnia in the model (OR=2.9, CI 1.55-5.43, P<.001). The presence of RLS symptoms is associated with depression in patients with CKD. This relationship remained significant even after accounting for insomnia. Sleep-independent mechanisms may also contribute to the association between RLS and depression in patients with CKD.

Health-related quality of life and clinical outcomes in kidney transplant recipients.

BACKGROUND Health-related quality of life (HRQoL) is an important outcome measure in patients with chronic kidney disease. It also has been shown repeatedly to predict mortality in various patient populations. In a prospective cohort study, we assessed the association between HRQoL and long-term clinical outcome in kidney transplant recipients. STUDY DESIGN Prospective prevalent cohort study. SETTING & PARTICIPANTS We collected sociodemographic parameters, medical and transplant history, and laboratory data at baseline from 879 prevalent kidney transplant recipients (mean age, 49 ± 13 [standard deviation] years; 58% men; and 17% with diabetes mellitus). PREDICTOR We assessed HRQoL using the KDQoL-SF (Kidney Disease Quality of Life Short Form) questionnaire and assessed depressive symptoms using the Center for Epidemiologic Studies-Depression Scale. OUTCOMES All-cause mortality and death-censored transplant loss or death with functioning transplant. Cox regression models and semiparametric competing-risks regression analyses were used to measure associations between HRQoL scores and outcomes. RESULTS Most examined HRQoL domains were associated with clinical outcome in unadjusted models. After adjusting for several important confounders, the 36-Item Short Form Health Survey (SF-36) Physical Composite Score and Physical Functioning and General Health Perception subscale scores remained independently associated with clinical outcomes. Every 10-point increase in SF-36 Physical Composite Score and Physical Functioning and General Health Perception scores was associated with 18% (HR, 0.82; 95% CI, 0.71-0.95), 11% (HR, 0.89; 95% CI, 0.84-0.94), and 7% lower risks of mortality (HR, 0.93; 95% CI, 0.88-1.00), respectively. LIMITATIONS Single-center study. CONCLUSIONS We showed that the SF-36 Physical Composite Score and Physical Functioning and General Health Perception KDQoL-SF domain scores are associated independently with increased risk of mortality in kidney transplant patients. Regular assessment of HRQoL may be a useful tool to inform health care providers about the prognosis of kidney transplant recipients. Additional studies are needed to assess whether interventions aimed at improving HRQoL would improve clinical outcomes in this patient population.

Periodic limb movements in sleep are associated with stroke and cardiovascular risk factors in patients with renal failure

Periodic limb movements in sleep (PLMS) is prevalent among dialysed patients and is associated with increased risk of mortality. Our study aimed to determine the prevalence of this disease in a sample of transplanted and waiting‐list haemodialysed patients. One hundred transplanted and 50 waiting‐list patients underwent polysomnography. Moderate and severe diseases were defined as periodic limb movements in sleep index (PLMSI) higher than 15 and 25 events h−1, respectively. The 10‐year coronary heart disease risk was estimated for all patients using the Framingham Score. Moreover, the 10‐year estimated risk of stroke was calculated according to the modified version of the Framingham Stroke Risk Profile. PLMS was present in 27% of the transplanted and 42% of the waiting‐list group (P = 0.094); the proportion of severe disease was twice as high in waiting‐list versus transplanted patients (32 versus 16%, P = 0.024). Patients with severe disease had a higher 10‐year estimated risk of stroke in the transplanted group [10 (7–17) versus 5 (4–10); P = 0.002] and a higher 10‐year coronary heart disease risk in both the transplanted [18 (8–22) versus 7 (4–14); P = 0.002], and the waiting‐list groups [11 (5–18) versus 4 (1–9); P = 0.032]. In multivariable linear regression models the PLMSI was associated independently with the Framingham cardiovascular and cerebrovascular scores after adjusting for important covariables. Higher PLMSI is an independent predictor of higher cardiovascular and cerebrovascular risk score in patients with chronic kidney disease. Severe PLMS is less frequent in kidney transplant recipients compared to waiting‐list dialysis patients.

Multimorbidity and the risk of restless legs syndrome in 2 prospective cohort studies

Objective: Our aim was to evaluate the association between the cumulative effect of comorbidity and the risk of restless legs syndrome (RLS) in 2 population-based German cohort studies. Methods: The Dortmund Health Study (DHS) (n = 1,312; median follow-up time: 2.1 years) and the Study of Health in Pomerania (SHIP) (n = 4,308; median follow-up time: 5.0 years) were used for the analyses. RLS was assessed at baseline and follow-up according to the RLS minimal criteria. A comorbidity index was calculated as a sum of the following conditions: diabetes, hypertension, myocardial infarction, obesity, stroke, cancer, renal disease, anemia, depression, thyroid disease, and migraine. The relationship between comorbidity and incident RLS was analyzed with multivariate logistic regression models. Results: An increase in the number of comorbid conditions at baseline predicted prevalent RLS (DHS: trend odds ratio [OR] = 1.24, 95% confidence interval [CI] 0.99–1.56; SHIP: trend OR = 1.34, 95% CI 1.18–1.52) and incident RLS (DHS: trend OR = 1.32, 95% CI 1.04–1.68; SHIP: trend OR = 1.59, 95% CI 1.37–1.85) after adjustment for several covariates. The ORs for incident RLS associated with 3 or more comorbid diseases (DHS: OR = 2.51, 95% CI 1.18–5.34; SHIP: OR = 4.30, 95% CI 2.60–7.11) were higher than the ORs for any single disease. Conclusions: Multimorbidity was a strong risk factor for RLS in these 2 population-based cohort studies. The results support the hypothesis that cumulative disease burden is more important than the presence of a specific single disease in the pathophysiology of RLS.

Incidence of restless legs syndrome in two population-based cohort studies in Germany

OBJECTIVES Prospective data about the new-onset of restless legs syndrome (RLS) are lacking. Our aim was to assess the incidence rate of RLS in the general population. METHODS RLS, defined by the minimal diagnostic criteria, was assessed twice in two independently conducted prospective population-based cohort studies in Germany. The Dortmund Health Study (DHS) had a mean follow-up of 2.2 years, and included 1312 participants, and the Study of Health in Pomerania (SHIP) followed 4308 participants for, on average, 5.2 years. RLS was assessed during face-to-face interviews in both studies at baseline and at follow-up in SHIP, and with mailed questionnaires at follow-up in DHS. RESULTS The age-standardized incidence rate of RLS was 22/1000 person-years (p-y) (cumulative incidence over the follow-up: 9.1%) in DHS and 9/1000 p-y (cumulative incidence: 7.0%) in SHIP. Women had a higher incidence rate than men (DHS: 27/1000 p-y vs. 17/1000 p-y, p=0.28; SHIP: 12/1000 p-y vs. 7/1000 p-y, p<0.001). There was a linear increase in RLS incidence rate with age in both studies. The persistence of RLS symptoms from baseline to follow-up was 47.4% in DHS and 41.5% in SHIP. CONCLUSION The incidence rate of RLS is high, while the persistence of RLS over time is low, suggesting that RLS symptoms vary considerably. The increased RLS incidence rate among women and the elderly is consistent with previous prevalence data.

Sleep disorders: impact on daytime functioning and quality of life

This article provides an overview of the daytime symptoms associated with the most common sleep disorders, namely insomnia, restless legs syndrome, obstructive sleep apnea syndrome and shift wake–sleep disorder. Psychological and social dysfunction resulting from these sleep disturbances are explained and discussed in detail. Health-related quality of life is a concept that reflects the changes in diverse aspects of subjective wellbeing of the patients due to an illness. Therefore, studies reporting quality-of-life issues associated with the aforementioned sleep disorders will also be presented. Finally, we review the limited data regarding the effects of treatment on quality-of-life outcomes.

The relationship between depressive symptoms and restless legs syndrome in two prospective cohort studies

Objective Cross-sectional studies suggest a strong association between depression and restless legs syndrome (RLS); however, the temporal relationship between the two disorders remains unknown. We tested whether the presence of clinically relevant depressive symptoms (CRDS) is a risk factor for subsequent RLS in the general population. The relationship between prevalent RLS and incident CRDS was also examined. Methods Two independent, prospective cohort studies with representative, age-stratified random samples, the Dortmund Health Study (DHS; n = 1312/1122 [baseline/follow-up], median follow-up time = 2.1 years) and the Study of Health in Pomerania (SHIP; n = 4308/3300, median follow-up time = 5.0 years) were analyzed. RLS was assessed in both studies according to the RLS minimal criteria, at baseline and at follow-up. CRDS were assessed by the Center for Epidemiologic Studies–Depression scale (a score of ≥16) in DHS only at baseline and by the Munich-Composite International Diagnostic-Screener in SHIP at baseline and at follow-up. Results Clinically relevant depressive symptoms at baseline were associated new-onset RLS in both studies (DHS: odds ratio [OR] = 1.94, 95% confidence interval [CI] = 1.09–3.44; SHIP: OR = 2.37, 95% CI = 1.65–3.40) after adjustment for age, sex, education, body mass index, smoking, physical activity, and the presence of various comorbidities. RLS at baseline was an independent risk factor of incident CRDS in SHIP (OR = 1.82, 95% CI = 1.10–3.00). Conclusions The presence of CRDS may be a risk factor for subsequent RLS. The relationship between the two disorders might be bidirectional because RLS also predicts incident depressive symptoms.

Sleep apnea is associated with cardiovascular risk factors among kidney transplant patients.

BACKGROUND AND OBJECTIVES We assessed the prevalence of obstructive sleep apnea (OSA) and its clinical correlates in a large sample of patients who received a kidney transplant (Tx). We also compared the prevalence of the disorder between dialysis patients who were on the waiting list for a Tx (WL) and Tx patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This was a cross-sectional study of 100 Tx and 50 WL patients who underwent one-night polysomnography (SLeep disorders Evaluation in Patients after kidney Transplantation [SLEPT] Study). Sociodemographic information and data about medication, comorbidity, and laboratory parameters were collected. RESULTS The prevalence of mild (apnea-hypopnea index [AHI] > or =5/h and <15/h), moderate (AHI > or =15/h and <30/h), and severe OSA (AHI > or =30/h) was 18, 11, and 14% in the Tx group and 28, 16, and 10% in the WL group, respectively. The AHI was significantly correlated with age (rho = 0.34), body mass index (rho = 0.45), neck circumference (rho = 0.4), abdominal circumference (rho = 0.51), and hemoglobin (rho = 0.24) in the Tx group. The proportion of Tx patients who were treated with three or more antihypertensive drugs was significantly higher in the OSA group (56 versus 31%; P = 0.022). Despite taking significantly more antihypertensive drugs, the average systolic BP was still higher in patients with versus without OSA (147 +/- 21 versus 139 +/- 18 mmHg; P = 0.059). CONCLUSIONS The prevalence of OSA is similar in Tx and WL patients and it may contribute to presence of hypertension in patients who receive a Tx.