Abstract: BACKGROUND: The incidence of fractures is substantially increased in patients with chronic kidney disease (CKD) compared to the general population. The factors associated with increased bone fracture in this population are not well understood. Vitamin D deficiency has been associated with decreased bone mass and higher incidence of fractures in the general population. In this study, we aimed to assess the association between fracture and vitamin D status and other factors potentially associated with fracture in patients on maintenance hemodialysis. METHODS: One hundred and forty-four patients were assessed and interviewed about previous low-trauma fractures. Evidence of fracture was obtained from medical records and also through patient interviews. Routine laboratory results were collected from medical records. Serum intact PTH (iPTH) and 25(OH) vitamin D(3) were measured. All patients underwent bone densitometry of the lumbar spine, femoral neck and distal radius. Bone quality was also assessed with quantitative bone ultrasound (QUS). Descriptive statistics, logistic regression models were used to analyze factors associated with fractures. RESULTS: One hundred and thirty patients were included in the final analysis. Patients with fractures (n = 21) had lower 25(OH) vitamin D(3) levels (15.8 nmol/l (interquartile range, IQR: 27) vs. 30.0 nmol/l (IQR: 28.5), P = 0.029), were more likely females, had longer duration of end-stage kidney disease, and lower bone mineral density (BMD) at the distal radius. QUS parameters were not associated with fractures. Multivariate analyses revealed that serum 25(OH) vitamin D(3) concentration, BMD at the radius, iPTH less than 100 pg/ml and history of fractures were independent predictors of new bone fracture after the initiation of dialysis therapy. CONCLUSION: Increased bone fragility in dialysis patients is associated with vitamin D deficiency and relative hypoparathyroidism in addition to reduced BMD at the radius. Further studies are needed to determine whether patients with vitamin D deficiency benefit from vitamin D supplementation to reduce fracture risk.
Abstract: BACKGROUND: Depression is associated with impaired quality of life and increased morbidity and mortality in patients with end-stage renal disease. Little is known about the prevalence and correlates of depression in kidney transplant recipients. In this study, we aimed to compare depressive symptoms between kidney transplant recipients and wait-listed dialysis patients and identify the correlates of depressive symptoms in the transplant recipient population. STUDY DESIGN: Observational cross-sectional study using the Center for Epidemiologic Studies Depression Scale (CES-D) to assess the severity of depressive symptoms. A cutoff score of 18 was used to identify the presence of depression. SETTING & PARTICIPANTS: 1,067 kidney transplant recipients and 214 wait-listed dialysis patients were asked to participate; the final analysis included 854 kidney transplant and 176 wait-listed dialysis patients, respectively. PREDICTORS: Sociodemographic and clinical variables. OUTCOME: Severity of depressive symptoms and presence of depression (CES-D score > or = 18). RESULTS: The prevalence of depression was 33% versus 22% in wait-listed versus transplant patients, respectively (P = 0.002). In multivariate regression, number of comorbid conditions, estimated glomerular filtration rate, perceived financial situation, and marital status were significant and independent predictors of depression in the transplant recipient group. Treatment modality was associated significantly with the presence of depression, even after adjustment for clinical and sociodemographic variables (OR, 2.01; 95% CI, 1.25-3.23; P = 0.004). LIMITATIONS: Self-reported measurement of depressive symptoms. CONCLUSIONS: The prevalence of depression is lower in transplant recipients than in wait-listed patients. However, one-fifth of transplant patients are still at high risk of clinically significant depression. Comorbid conditions, socioeconomic status, and treatment modality predicted depressive symptoms in patients with end-stage renal disease.
Abstract: BACKGROUND: The relationship between parathyroid function, an important determinant of bone turnover, and bone mineral density (BMD) in patients with chronic kidney disease is not fully understood. We wanted to analyze the association between BMD and parathyroid function in hemodialysis patients in details. METHODS: In a cross-sectional design, data from 270 patients (age 55 +/- 15 years, 60% men, all Caucasian) on maintenance hemodialysis were analyzed. All patients underwent dual energy X-ray absorptiometry of the lumbar spine (LS), femoral neck (FN) and distal radius (DR). In addition to routine laboratory tests, blood samples were collected for iPTH, serum markers of bone metabolism (alkaline phosphatase, type I collagen crosslinked-C-telopeptide) and 25OH vitamin D. RESULTS: Based on Z-scores, bone mineral density was moderately reduced only at the femoral neck in the total cohort. The average Z-score of the "low PTH" group (iPTH < 100 pg/ml) was not different from the Z-score of patients with iPTH in the "target range" (100-300 pg/ml) at any measurement site. While iPTH was negatively correlated with BMD at all measurement sites in patients with iPTH > 100 pg/ml (rho = -0.255, -0.278 and -0.251 for LS, FN and DR, respectively, P < 0.001 for all), BMD was independent of iPTH in patients with iPTH < 100 pg/ml. Furthermore, iPTH was not associated with serum markers of bone metabolism, but these markers were negatively correlated with BMD in the "low PTH" group. CONCLUSIONS: Low PTH levels are not associated with low BMD in patients with end-stage kidney disease. Furthermore, bone metabolism seems to be independent of iPTH in patients with relative hypoparathyroidism likely reflecting skeletal resistance to PTH.
Abstract: INTRODUCTION: Impaired kidney function is common in kidney-transplanted patients and complications of chronic kidney disease (CKD), such as mineral and bone disorders (MBD) are also prevalent in this population. Similarly to other stages of CKD, increasing evidence supports the association between MBD and cardiovascular risk after kidney transplantation as well. Still, little is known about the prevalence, clinical correlates of MBD and its management in transplanted patients. In this study, we aimed to examine the characteristics of MBD and its associations with clinical parameters in a large prevalent cohort of patients after kidney transplantation. METHODS: Nine hundred and ninety stable patients followed at a single kidney transplant outpatient clinic were included in the study. Detailed medical history, demographic data and routine laboratory results, including Ca, P and intact PTH were collected. Estimated GFR was calculated using the abbreviated MDRD formula, patients were stratified into three groups based on eGFR. Target levels for Ca, P and iPTH were based on CKD stages according to the NKF-K/DOQI guidelines. Standard statistical procedures, binomial and multinomial regressions were used in the analysis. RESULTS: The mean age was 51 years, 57% were males and 21% were diabetic, with 72 months (median) post-transplantation. Most of the patients were in CKD stage 3. Serum phosphorus showed strong negative correlation with graft function in CKD stages 4-5 (r = -0.633, P < 0.001). Hyperphosphatemia was independently associated with the time spent on dialysis before transplantation, serum iPTH and CKD stages 4-5. iPTH showed negative correlation with eGFR in CKD stages 3-5 (rho = -0.289, P < 0.001) and weak positive correlation with time spent on dialysis prior to transplant (rho = 0.114, P < 0.001). Both hyperparathyroidism (42%) and relative hypoparathyroidism (15%) were frequent. The prescription of P-binders (6%) and vitamin D analogs (33%) was sporadic. CONCLUSION: Disturbances of bone and mineral metabolism after transplantation are prevalent and are strongly correlated with the kidney function, similarly to non-transplanted CKD patients. MBD in this population is not adequately managed.
Abstract: INTRODUCTION: To date, only a few, at times conflicting, reports suggested that renal function and mortality are associated in kidney-transplanted patients. In our prevalence cohort study, we tested the hypothesis that renal function is associated with mortality in transplanted patients. METHODS: Data from 985 transplanted patients were analyzed. Socio-demographic parameters, laboratory data, medical and transplant history, type of immunosuppression and estimated glomerular filtration rate were tabulated at baseline. Data on 5-year outcome were collected prospectively. RESULTS: In multivariate Cox proportional hazard models, the estimated glomerular filtration rate measured at baseline significantly predicted mortality [hazard ratio (HR)(for each 10 ml/min decrease) = 1.271; 95% confidence interval (CI): 1.121-1.440] after adjustment for several covariables. Additionally, in multivariate Cox proportional hazard models, chronic kidney disease stage 4-5 (HR = 2.678; 95% CI: 1.494-4.802) significantly increased the mortality hazard compared to chronic kidney disease stage 1-2. CONCLUSIONS: Renal function is significantly and independently associated with mortality over 5 years in kidney-transplanted patients among whom mycophenolate mofetil use was very prevalent.
Abstract: Disorders of bone and mineral metabolism affect almost all patients with advanced chronic kidney disease (CKD). High prevalence of decreased bone mineral density has been reported in this population; however, the role and diagnostic utility of bone density measurements are not well established. The incidence of bone fractures is high in patients with ESRD, but the association between fractures and bone density is not obvious. A recent meta-analysis suggested that decreased density at the radius might be associated with higher overall fracture risk. Changes in bone mineral density reflect several underlying pathological processes, such as vitamin D deficiency, estrogen deficiency and changes in bone turnover. The response of bone to these factors and processes is not uniform: it can vary in different compartments of the same bone or in different bones of the skeleton. Therefore, it is important to differentiate between the various types of bone. This may be possible by proper selection of the measurement site or using methods such as quantitative bone computed tomography. Previous studies used different methods and measured bone mineral density at diverse sites of the skeleton, which makes the comparison of their results very difficult. The association between changes in bone mineral metabolism and cardiovascular mortality is well known in ESRD patients. Studies also suggest that low bone density itself might be an indicator for high risk of cardiovascular events and poor overall outcome in this population. Some of the risk factors of low bone mineral density, such as vitamin D or estrogen deficiency, are potentially modifiable. Further studies are needed to elucidate if interventions modifying these risk factors will have an impact on clinical outcomes. In this review, we discuss the options for and problems of assessment of bone density and summarize the literature about factors associated with low bone density and its link to clinical outcomes in patients on maintenance dialysis.
Abstract: Although anemia is a known risk factor of mortality in several patient populations, no prospective study to date has demonstrated association between anemia and mortality in kidney-transplanted patients. In our prospective cohort study (TransQol-HU Study), we tested the hypothesis that anemia is associated with mortality and graft failure (return to dialysis) in transplanted patients. Data from 938 transplanted patients, followed at a single outpatient transplant center, were analyzed. Sociodemographic parameters, laboratory data, medical history and information on comorbidity were collected at baseline. Data on 4-year outcome (graft failure, mortality or combination of both) were collected prospectively from the patients' charts. Both mortality and graft failure rate during the 4-year follow-up was significantly higher in patients who were anemic at baseline (for anemic vs nonanemic patients, respectively: mortality 18% vs. 10%; p < 0.001; graft failure 17% vs 6%; p < 0.001). In multivariate Cox proportional hazard models the presence of anemia significantly predicted mortality (HR = 1.690; 95% CI: 1.115-2.560) and also graft failure (HR = 2.465; 95% CI: 1.485-4.090) after adjustment for several covariables. Anemia, which is a treatable complication, is significantly and independently associated with mortality and graft failure in kidney-transplanted patients.
Abstract: OBJECTIVE: Restless legs syndrome (RLS) is associated with insomnia and impaired quality of life (QoL) in patients on maintenance dialysis; however, no information has been published on the association of RLS and QoL in kidney-transplanted patients. In a cross-sectional study, we analyzed the complex relationship between RLS, insomnia, and health-related QoL in kidney-transplanted patients. METHODS: In a cross-sectional survey at a single transplant center, 1067 patients were invited to participate. Complete data set was available from 785 kidney-transplanted patients. The RLS Questionnaire and the Athens Insomnia Scale were used to assess the prevalence of RLS and insomnia, respectively. QoL was measured using the Kidney Disease QoL-SF Questionnaire. RESULTS: Patients with RLS were three times more likely to have insomnia than patients without RLS (29% vs. 9%, P=.001), and the presence of RLS was a significant and independent predictor of insomnia in multivariate analysis. The presence of RLS was independently associated with impaired health-related QoL along several QoL domains after statistical adjustment for clinical and sociodemographic covariables. Importantly, this association remained significant even after adjusting for insomnia for some QoL domains. CONCLUSION: RLS is associated with poor sleep, increased odds for insomnia, and impaired QoL in kidney-transplanted patients. Our results suggest that both sleep-related and sleep-independent factors may contribute to the association of RLS and QoL.
Abstract: BACKGROUND: Recent studies confirmed that sleep disorders have a significant impact on various aspects of health in patients at different stages of chronic kidney disease. At the same time, there is an almost complete lack of information on the prevalence and correlates of insomnia in kidney transplant recipients. METHODS: In a cross-sectional study, the Athens Insomnia Scale was used to assess the prevalence of insomnia in a large sample of kidney transplant recipients compared with wait-listed dialysis patients and also a matched group obtained from a nationally representative sample of the Hungarian population. RESULTS: The prevalence of insomnia was 15% in wait-listed patients, whereas it was only 8% in transplant recipients (P < 0.001), which, in turn, was not different from the prevalence of this sleep problem in the sample of the general population (8%). Prevalences of insomnia in the transplant group were 5%, 7%, and 14% for the groups with glomerular filtration rates (GFRs) greater than 60 mL/min (> 1.00 mL/s), 30 to 60 mL/min (0.50 to 1.00 mL/s), and less than 30 mL/min (< 0.5 mL/s), respectively (P < 0.01). However, estimated GFR was no longer associated significantly with insomnia in the transplant population after statistical adjustment for several covariates. In a multivariate model, insomnia was significantly and independently associated with treatment modality (transplantation versus wait listing), as well as the presence of depression, restless legs syndrome, and high risk for obstructive sleep apnea syndrome, and with self-reported comorbidity. CONCLUSION: The prevalence of insomnia was substantially less in the transplant group than in wait-listed dialysis patients and similar to that observed in the general population. Because this condition potentially is treatable, attention should be directed to the appropriate diagnosis and management of insomnia in the kidney transplant recipient population.
Abstract: BACKGROUND: In a cross-sectional study, we analysed the complex relationship between restless legs syndrome (RLS), insomnia and specific insomnia symptoms and health-related quality of life (QoL) in patients on maintenance dialysis. METHODS: Data were obtained from 333 patients on chronic maintenance dialysis. To assess the prevalence of RLS, we used the RLS Questionnaire (RLSQ). The Athens Insomnia Scale (AIS) was used to assess insomnia and QoL was measured with the Kidney Disease Quality-of-Life Questionnaire. RESULTS: The prevalence of RLS was 14%. The number of comorbid conditions was significantly higher in patients with vs without RLS (median: three vs two; P<0.05). RLS patients were twice as likely to have significant insomnia as patients without RLS (35% vs 16%; P<0.05). Furthermore, RLS was associated with impaired overall sleep quality (median AIS score: 8 vs 4; P<0.01) and poorer QoL. RLS was a significant and independent predictor of several of the QoL domains after statistical adjustment for clinical and socio-demographic covariables. Importantly, this association remained significant even after adjusting for sleep quality. CONCLUSIONS: RLS is associated with poor sleep, increased odds for insomnia and impaired QoL in patients on maintenance dialysis. Based on the present results, we suggest that both sleep-related and sleep-independent factors may confer the effect of RLS on QoL.
Abstract: BACKGROUND: There is an almost complete lack of information on the epidemiology of sleep disorders in kidney-transplanted patients. In this report the authors assess the prevalence and clinical correlates of restless legs syndrome (RLS) in kidney-transplanted (Tx) patients. They also analyze the impact of declining renal function on this condition in the Tx population. Finally, the prevalence of RLS was compared between waitlisted dialysis patients (WL), and the Tx group. METHODS: In a cross-sectional study enrolling 992 patients (816 Tx and 176 WL), the presence of RLS was assessed using the Restless Legs Syndrome Questionnaire. Clinical and sociodemographic data were collected from the patients' medical records. RESULTS: In transplanted patients, the prevalence of RLS was 4.8%. RLS was associated strongly with declining renal function. In groups formed on the basis of estimated glomerular filtration rate (eGFR), the prevalence of RLS was 1.8%, 5.1%, 6.5%, and 23.5% in patients with eGFR greater than 60 mL/min/1.73 m 2 ; eGFR 30 to 59 mL/min/1.73 m 2 ; eGFR 15 to 29 mL/min/1.73 m 2 ; and eGFR less than 15 mL/min/1.73 m 2 , respectively (P < 0.001). There was also a significant association between RLS and lower serum hemoglobin, higher number of self-reported comorbid conditions, and higher prevalence of iron deficiency. RLS was significantly less frequent in patients taking steroids than in patients not taking this medication (4% versus 9%, P < 0.05). In multivariate analysis, not taking steroids, eGFR, self-reported comorbidity, and iron deficiency were significant and independent predictors of RLS. Dialysis treatment was associated with increased odds for RLS (odds ratio 2.2; 95% confidence interval 1.11 to 4.35; P < 0.05) even after adjusting for serum hemoglobin and comorbidity. CONCLUSION: The prevalence of RLS is significantly lower in Tx patients than in patients on maintenance dialysis. Declining renal function is associated with increasing prevalence of the condition.
Abstract: AIMS: An increasing amount of evidence suggests that 25-hydroxy vitamin D3 (25(OH)D3) may contribute to the bone health of patients with chronic kidney disease (CKD). The underlying vitamin D status of these patients, however, has often been neglected. In a cross-sectional study we assessed the association between vitamin D status and parathyroid function, bone turnover, bone mass and structure in patients on maintenance hemodialysis. METHODS: 69 patients on maintenance hemodialysis were assessed by bone densitometry (DEXA) and quantitative bone ultrasound (QUS). Serum 25-hydroxy vitamin D3 levels, serum markers of bone turnover and clinical data were tabulated. RESULTS: A high prevalence of potentially significant vitamin D3 deficiency was found in this patient group: 59% of the patients had a 25(OH)D3 level below 20 nmol/l. There was a significant negative correlation between serum 25(OH)D3 levels and serum intact parathyroid hormone (iPTH) (r = -0.231, p < 0.05), and this association remained significant after controlling for potential covariables. Furthermore, we show here that serum 25(OH)D3 concentration is positively correlated with bone mineral density (BMD) measured at the radius (r = 0.424, p < 0.01). Finally, we show for the first time that 25(OH)D3 levels are significantly and independently correlated with broadband ultrasound attenuation (beta = 0.262, p < 0.05) measured with calcaneal quantitative bone ultrasound (QUS) in patients with chronic renal failure. CONCLUSION: Vitamin D3 deficiency may contribute to the impaired bone health of patients on maintenance dialysis.
Abstract: BACKGROUND: Although a known cardiovascular risk factor, anemia in the renal transplant recipients has only recently been receiving an increasing attention. METHODS: In a cross-sectional study, data was obtained from 959 patients followed at a single outpatient transplant clinic. Based on the guideline of the American Society of Transplantation, anemia was defined as hemoglobin (Hb) < or =130 g/L in males and < or =120 g/L in females. RESULTS: About one-third (34%) of the patients were anemic. The prevalence of anemia was comparable in males and females. Serum Hb concentration was significantly correlated with the estimated glomerular filtration rate (eGFR) (abbreviated modification of diet in renal disease formula) (r = 0.266, p < 0.001), serum transferrin (r = 0.268, p < 0.001) and serum albumin (r = 0.196, p < 0.001). None of the immunosuppressive medications or the use of angiotensin converting enzyme inhibitors was associated with a higher likelihood of anemia. In multivariate analysis the eGFR, serum albumin and serum transferrin, potential markers of nutritional status and/or chronic inflammation, and also iron deficiency were independently and significantly associated with anemia. Erythropoietin was administered only to 63 (19%) anemic patients. CONCLUSIONS: Post-transplant anemia is a prevalent and under-treated condition. Based on our results we suggest that, besides other factors, protein/energy malnutrition and/or chronic inflammation may be independently associated with anemia. Further studies are needed to determine whether the presence of anemia and its treatment will have an impact on long-term outcomes of this population.
Abstract: OBJECTIVES: The objectives of this study were to compare the factor structure and to assess the reliability of the Hungarian version of the Illness Intrusiveness Rating Scale (IIRS), testing internal validity and employing simultaneous confirmatory factor analysis (SCFA) in two large samples of North American versus Hungarian patients with end-stage renal disease (ESRD). METHODS: Translation was conducted according to current recommendations. Following pilot testing, 365 maintenance haemodialysis patients completed the scale. Hungarian data were compared with IIRS data from North American ESRD patients undergoing maintenance hemodialysis to evaluate item bias (Group x Item ANOVA). RESULTS: Confirmatory factor analyses indicated a good fit between the previously hypothesized three-factor model ("relationships and personal development", "intimacy", and "instrumental" life domains) of the original English version and the Hungarian translation. Although statistically significant (P<.05), the effect size for the Groups x Items interaction was not substantial. Internal consistency was very good (Cronbach's alpha=.80) for the total score, and, although somewhat lower than ideal, it was still in the acceptable range for the subscales (.64-.67). These numbers are similar to values reported for the original English version. Test-retest reliability was also acceptable. CONCLUSION: The Hungarian translation of the IIRS has the same three-dimensional factor structure as the original English-language version does. Furthermore, it is sufficiently reliable for research applications. These features satisfy important requirements of cultural equivalence.
