Physical performance and clinical outcomes in dialysis patients: a secondary analysis of the EXCITE trial.

Background/Aims: Scarce physical activity predicts shorter survival in dialysis patients. However, the relationship between physical (motor) fitness and clinical outcomes has never been tested in these patients. Methods: We tested the predictive power of an established metric of motor fitness, the Six-Minute Walking Test (6MWT), for death, cardiovascular events and hospitalization in 296 dialysis patients who took part in the trial EXCITE (ClinicalTrials.gov Identifier: NCT01255969). Results: During follow up 69 patients died, 90 had fatal and non-fatal cardiovascular events, 159 were hospitalized and 182 patients had the composite outcome. In multivariate Cox models - including the study allocation arm and classical and non-classical risk factors - an increase of 20 walked metres during the 6MWT was associated to a 6% reduction of the risk for the composite end-point (P=0.001) and a similar relationship existed between the 6MWT, mortality (P<0.001) and hospitalizations (P=0.03). A similar trend was observed for cardiovascular events but this relationship did not reach statistical significance (P=0.09). Conclusions: Poor physical performance predicts a high risk of mortality, cardiovascular events and hospitalizations in dialysis patients. Future studies, including phase-2 EXCITE, will assess whether improving motor fitness may translate into better clinical outcomes in this high risk populatio

Effect of a home based, low intensity, physical exercise program in older adults dialysis patients: A secondary analysis of the EXCITE trial

Background: Older adults dialysis patients represent the frailest subgroup of the End Stage Renal Disease (ESRD) population and physical exercise program may mitigate the age-related decline in muscle mass and function. Methods: Dialysis patients of the EXCITE trial aged > 65 years (n = 115, active arm, n = 53; control arm, n = 62) were submitted in random order to a home based, low intensity physical exercise program. At baseline and 6 months after exercise training 6-min walking distance (6MWD) and 5-time sit-to-stand test (5STS) were performed, and quality of life (QoL) was tested. Results: The training program improved both the 6MWD (6-months: 327 \ub1 86 m versus baseline: 294 \ub1 74 m; P < 0.001) and the 5STS time (6-months: 19.8 \ub1 5.6 s versus baseline: 22.5 \ub1 5.1 s; P < 0.001) in the exercise group whereas they did not change in the control group (P = 0.98 and 0.25, respectively). The between-arms differences (6 months-baseline) in the 6MWD (+ 34.0 m, 95% CI: 14.4 to 53.5 m) and in the 5STS time changes (- 1.9 s, 95% CI: -3.6 to - 0.3 s) were both statistically significant (P = 0.001 and P = 0.024, respectively). The cognitive function dimension of QoL significantly reduced in the control arm (P = 0.04) while it remained unchanged in the active arm (P = 0.78) (between groups difference P = 0.05). No patient died during the trial and the training program was well tolerated. Conclusions: This secondary analysis of the EXCITE trial shows that a home-based, exercise program improves physical performance and is well tolerated in elderly ESRD patients. Trial registration: The trial was registered in ClinicalTrials.Gov (Clinicaltrials.gov identifier: NCT01255969) on December 8, 2010

Effort-Reward Imbalance, Workabilty and Utility Estimates in Chronic Kidney Failure

In the US about 300.000 Chronic Kidney Failure (CKF) patients are of the working age. Despite longer survival and improved quality of life (QOL), the employment rate of CKF patients is low. Factors associated to job retention after disease onset are under-investigated. We examined the relationship between Effort-Reward Imbalance (ERI), Workability, and QOL in Hemodialysis (HD). Also, we examined the association of Workability and sick leave rate (SL) in the post-enrollment month. Forty employed HD patients answered a self-administered survey including the ERI, the Work Ability Index (WAI ), and the Kidney Disease QOL 36 items (KDQOL-36) questionnaires. We also computed SF-6D utility index, a tool suitable for cost-benefit analyses. We recorded 4-week SL by computer-assisted telephone interview. We tested the associations of ERI quintiles with WAI , KDQOL-36 and utility estimates with Spearman\u2019s partial correlation adjusted for age, hourly income (HI), and number of comorbidities (NoC). Patients were classified by WAI scores (Group A if WAI 6427, Group B otherwise). Differences in SL between groups were assessed by Mann-Whitney test. Sample mean age was 46.9 (SD=8.2). Almost 95% of subjects reported at least one concurrent disease and 65% reported 3 or more comorbidities. Sixteen (40%) were hand laborer. Only 3 (7%) reported ERI values indicating disequilibrium between job efforts and rewards. However, WAI (\u3c1= -0.41, p<0.012), SF-6D (\u3c1= -0.47, p<0.001) and KDQOL scale (\u3c1= -0.48, p<0.001) were negatively correlated to ERI after adjusting for age, HI and NoC. The mean SL was 5.9 days/month (SD=10.4 days/month). Subjects with poor WAI reported 11.8 sick days/month compared to 4.0 sick days/month for subjects with moderate or higher WAI (p=0.049). Our data showed that workplace psychosocial environment might have a significant effect on patients\u2019 clinical care, workability, and absenteeism rates. It provides the rational for interventional studies aimed at sustaining HD patients\u2019 job retention. Effect of Exposure in Vivo on Work Functioning: Systematic Review Erik Noordik* Academic Medical Center (Amsterdam, Netherlands) Background: Anxiety disorders are associated with functional disability, sickness absence and decreased productivity. Effective treatments of anxiety disorders result in remission of symptoms; however this does not automatically generate complete functional recovery at work. This study is a systematic review of the effect of exposure in vivo in anxiety treatment on work-related outcomes for workers. PTSD studies were excluded as a category that needs a specific approach. Method: A systematic search was conducted using text words based on bibliographic research. Inclusion and exclusion criteria were defined. After the search, we used the snowball method based on reviews, references, citations and authors of included publications. We assessed the quality of included publications by a checklist. High and low quality studies were incorporated in an evidence synthesis evaluating the level of evidence. Results: The systematic search resulted in two included publications, by snowballing we found another three. Four studies were aimed at Obsessive Compulsive Disorder (OCD), while one study included a mixed group of participants with either OCD or severe phobias. All studies were rated as being of low quality. Using the rules for evidence synthesis, we found conflicting evidence for a positive relationship between exposure in vivo in anxiety treatment and workrelated outcomes. Conclusion: We found five relevant studies. All studies concerned patients with Obsessive Compulsive Disorders (OCD). For these patients, we found conflicting evidence that exposure in vivo is effective on work-related outcomes. There is a lack of high quality intervention studies aimed at anxiety disorders, apart from PTSD, measuring work-related outcomes

Calcificazioni cardiovascolari e aterosclerosi accelerata in corso di uremia

Cardiovascular disease is the first cause of morbidity and mortality in dialysis patients. Hyperphosphatemia and elevated serum calcium-phosphate levels have recently been investigated as inducing factors on extraskeletal calcification in this population. In vitro studies demonstrated that human aortic smooth muscle cells calcify when incubated in a high phosphate medium, where calcium and calcitriol are not changed. Furthermore, the lack of inhibitory proteins, such as fetuin and matrix Gla protein, is a possible main determinant of calcium-phosphate deposition in soft tissues. The classical treatment of hyperphosphatemia and secondary hyperparathyroidism in dialysis patients consists of calcium-based phosphate binders and calcitriol administration. Unfortunately, this "first-generation" therapy is not free of dramatic side effects. New free-calcium and -aluminum phosphate binders, new vitamin D metabolites, and calcimimetics are examples of "second-generation" therapies that may prevent vascular calcification and possibly prevent some of the burden of cardiovascular disease in uremia

Nuove acquisizioni nella patogenesi dell'iperparatiroidismo secondario = New insights in the pathogenesis of secondary hyperparathyroidism

Parathyroid gland growth is a major cause of secondary hyperparathyroidism in renal failure. It is well known that high serum phosphate levels, low serum calcium levels and vitamin D deficiency are the three promoters of parathyroid hyperplasia in renal failure. Recent studies have investigated in depth the potential role of growth factors (transforming growth factor alpha) and their receptors (epidermal growth factor receptor) in the pathogenesis of parathyroid cell hyperplasia in chronic renal failure. The identification of molecular mechanisms involved in calcium, phosphate and vitamin D manipulations in an experimental renal failure model could help design more effective therapy for secondary hyperparathyroidism in uremic patient

Cardiovascular calcification and accelerated atherosclerosis in chronic kidney disease

Cardiovascular disease is the first cause of morbidity and mortality in dialysis patients. Hyperphosphatemia and elevated serum calcium-phosphate levels have recently been investigated as inducing factors on extraskeletal calcification in this population. In vitro studies demonstrated that human aortic smooth muscle cells calcify when incubated in a high phosphate medium, where calcium and calcitriol are not changed. Furthermore, the lack of inhibitory proteins, such as fetuin and matrix Gla protein, is a possible main determinant of calcium-phosphate deposition in soft tissues. The classical treatment of hyperphosphatemia and secondary hyperparathyroidism in dialysis patients consists of calcium-based phosphate binders and calcitriol administration. Unfortunately, this "first-generation" therapy is not free of dramatic side effects. New free-calcium and -aluminum phosphate binders, new vitamin D metabolites, and calcimimetics are examples of "second-generation" therapies that may prevent vascular calcification and possibly prevent some of the burden of cardiovascular disease in uremia

Work ability and health status in dialysis patients

End stage renal disease (ESRD) is a highly disabling state, conditioning not only patients' quality of life but also the maintenance of their job and social status. The access to work of ESRD patients is a problem which involves hundreds of thousand people in the industrial world and their number will increase in the next years. One of the prominent goals of medicine is to help patients to maintain their ability to participate in social life and to recover their efficiency. The beginning of dialysis seems to be a critical moment for the onset of working disability. Indeed, a fall from 42% to 6% in patients' occupational rates has been recorded, respectively 6 months before and one year after the beginning of dialysis. The variables which may affect the employability of ESRD patients can be grouped into four main categories: demographic, psychological, medical and occupational. Patients' occupational status correlates only partially to their demographic data and to the parameters normally used for the clinical-functional assessment. On the other hand, the subjective dimension plays a significant role in determining the degree of patients' working activity. Unfortunately, few data are available about work type and organization influence. We believe that this area of clinical research is crucial, despite the fact that it has received very little attention. A comprehensive understanding of those factors determining employability, and of the effects of unemployment on health status and life styles, will provide knowledge for a multidisciplinary patient-centered approach to treat and to rehabilitate patients on dialysis

Occupational stress is associated with impaired work ability and reduced quality of life in patients with chronic kidney failure

Background: about 300,000 patients in the united states with chronic Kidney Failure (cKF) are of working age, but up to 70% lose their job within the first year of renal replacement therapy. No study has examined how work ability and perceived health are influenced by the subjects’ adjustment to their job. We assessed the association of occupational stress (Effort-Reward Imbalance, ERI), work ability (WaI) and health-related quality of life (QoL) in hemodialysis. Methods: 40 employed hemodialysis patients completed a self-administered questionnaire. associations between ERI, short Form 12 (sF-12), short Form – 6 Dimensions (sF-6D), Kidney Disease QOL - 36 (KDQOL-36) and WaI were tested with partial spearman’s correlation adjusted for age, income, and comorbidity burden. results: study subjects were mainly low-income (82%), african-american (73%), men (75%); 16 were manual laborers and 9 worked in the industrial sector. study subjects reported low levels of Occupational stress: ERI scores indicated an imbalance between Job Efforts and Rewards in only 3 subjects. Nevertheless, ERI scores were inversely and strongly associated with WaI (ρ=-0.41, p<0.012) and all QoL scales even after adjustment for known confounders. conclusion: Our study suggests that psychosocial workplace factors may play a substantial role in modulating patients’ health perception and ability to continue working. the causal relationship between Occupational stress, perceived health, and work ability should be further investigated. Occupational health professionals and nephrologists should closely collaborate to meet the needs of occupationally active hemodialysis patients

Facial changes in adult uremic patients on chronic dialysis: possible role of hyperparathyroidism

BACKGROUND: Uremic patients on regular dialytic treatment (RDT) are often affected by a complex metabolic syndrome leading to osteodystrophy. Bone changes are primarily due to high bone turnover, often combined with a mineralization defect leading to increased bone fractures and bone deformities. Although rarely considered, the craniofacial skeleton represents one of the peculiar targets of this complex metabolic disease whose more dramatic pattern is a form of leontiasis ossea. This complication, although described, has never been evaluated in depth nor quantitatively assessed. In order to assess facial deformities in uremic conditions and to understand the possible relation with hyperparathyroidism, we undertook a quantitative evaluation of soft facial structures in a cohort of uremic patients undergoing RDT. METHODS: The three-dimensional coordinates of 50 soft-tissue facial landmarks were obtained by an electromagnetic digitizer in 10 male and 10 female patients with chronic renal insufficiency aged 53-81 years, and in 34 healthy individuals of the same age, ethnicity and sex. Uremic patients were enrolled according to hyperparathyroid status (PTH 500 pg/mL). From the landmarks, facial distances, angles and volumes were calculated according to a geometrical face model. RESULTS: Overall, the uremic patients had significantly larger facial volumes than the reference subjects. The effect was particularly evident in the facial middle third (maxilla), leading to an inversion of the mandibular-maxillary ratio. Facial dimensions were increased in all three spatial directions: width (skull base, mandible, nose), length (nose, mandible), and depth (mid face, mandible). The larger maxilla was accompanied by a tendency to more prominent lips (reduced interlabial angle). Some of the facial modifications (nose, lips, mandible) were significantly related to the clinical characteristics of the patients (age, duration of renal insufficiency and PTH levels). CONCLUSIONS: This report, the first in the literature, shows that facial structures of uremic patients are enlarged in comparison with matched normal subjects and that increased bone turnover could be responsible--at least in part--for facial bone changes

Obesity and cardiac risk after kidney transplantation : experience at one center and comprehensive literature review

BACKGROUND: The cardiac implications of obesity in kidney transplant recipients are not well-described. METHODS: We examined associations of body mass index (BMI) at transplant with posttransplant cardiac risk among 1102 renal allograft recipients at a single center in 1991 to 2004. Cumulative posttransplant incidences of congestive heart failure (CHF), atrial fibrillation (AF), myocardial infarction, and a composite of these cardiac diagnoses were estimated by the Kaplan-Meier method. Bivariate (hazards ratio) and covariate (adjusted hazards ratio) relationships of BMI increments with cardiac risk were modeled by Cox's regression. We also systematically reviewed the literature on BMI and cardiac events after transplant. RESULTS: In the local data, 5-year cumulative incidence of any cardiac diagnosis rose from 8.67% to 29.35% across the lowest to highest BMI quartiles (P=0.02), driven primarily by increases in CHF and AF. In contrast, the rate of myocardial infarction did not differ by BMI quartile (P=0.56). Each 5 U BMI increase predicted 25% higher risk of the cardiac composite (hazards ratio 1.25, 95% CI 1.07-1.47, P=0.005), a relationship that persisted with significance after covariate adjustment (adjusted hazards ratio 1.19, 95% CI 1.00-1.43, P=0.049). BMI independently predicted cardiac risk in subcohorts with pretransplant heart disease and with nondiabetic renal failure. Data from 26 original articles support BMI as a risk factor for posttransplant CHF and AF, whereas findings for coronary/ischemic outcomes are inconsistent and predominantly negative. CONCLUSIONS: High BMI at transplant predicts increased cardiac risk, especially of CHF and AF. Further research should examine whether obesity treatment modifies cardiac risk after kidney transplantation