Okdeep Kaur

Predictors and consequences of fatigue in prevalent kidney transplant recipients.

Background Fatigue has been underinvestigated in stable kidney transplant recipients (KTRs). The objectives of this study were to investigate the nature, severity, prevalence, and clinical awareness of fatigue in medically stable KTRs, examine the impact of fatigue on quality of life (QoL), and explore the underlying causes of posttransplantation fatigue. Methods This single-center cross-sectional study enrolled 106 stable KTRs. Multi-dimensional Fatigue Inventory-20 was used to measure five fatigue dimensions: General Fatigue, Physical Fatigue, Reduced Activity, Reduced Motivation, and Mental Fatigue. Clinical awareness of fatigue was determined by reviewing medical records. QoL was assessed by Medical Outcomes Study Short Form-36 Questionnaire. Demographic, clinical, psychosocial, and behavioral parameters were evaluated as fatigue predictors. Results Fatigue was found in 59% of KTRs. Only 13% had this symptom documented in medical records. Fatigue in KTRs was in the same range as chronically unwell patients, with Physical Fatigue, Reduced Activity, and Reduced Motivation approached levels observed in chronic fatigue syndrome. All fatigue dimensions significantly and inversely correlated with QoL (P<0.001 for all associations). Demographic predictors were male, older age, and non-Caucasian ethnicity (P⩽0.05 for all associations). Clinical predictors included elevated highly sensitive C-reactive protein (inflammation), decreased estimated glomerular filtration rate (graft dysfunction), and reduced lean tissue index (P⩽0.05 for all associations). Psychosocial and behavioral predictors were inferior sleep quality, anxiety, and depression (P<0.01 for all associations). Conclusions Fatigue is common and pervasive in clinically stable KTRs. It is strongly associated with reduced QoL. This study identified modifiable fatigue predictors and sets the scene for future interventional studies.

Cardiovascular, Muscular and Perceptual Contributions to Physical Fatigue in Prevalent Kidney Transplant Recipients

Physical fatigue is debilitating and common among kidney transplant recipients (KTRs). This study investigated the mechanistic aetiology of physical fatigue in this setting through examinations of muscle mass, muscular and cardiovascular function, and perceived exertion. The incidence of physical fatigue, its association with quality of life (QoL), and the predictors of perceived exertion, were evaluated. This single‐centre observational cross‐sectional study enrolled 55 KTRs. Muscle mass was quantified using dual‐energy x‐ray absorptiometry. Muscular function was assessed by jumping mechanography. Cardiovascular function (maximal oxygen consumption and oxygen pulse) was estimated during submaximal exercise testing, with perceived exertion determined using age‐adjusted Borg scale‐ratings. Physical fatigue was measured using Multi‐Dimensional Fatigue Inventory‐20. QoL was assessed using Medical Outcomes Study Short Form‐36. Demographic, clinical, nutritional, psychosocial and behavioural predictors of perceived exertion were assessed. Of clinical importance, increased perceived exertion was the only independent predictor of physical fatigue (P = 0.001), with no association found between physical fatigue and muscular or cardiovascular parameters. Physical fatigue occurred in 22% of KTRs, and negatively impacted on QoL (P < 0.001). Predictors of heightened perception included anxiety (P < 0.05) and mental fatigue (P < 0.05). Perception is a key determinant of physical fatigue in KTRs, paving the way for future interventions.

Hypervolemia and blood pressure in prevalent kidney transplant recipients.

Background The prevalence and consequences of hypervolemia in kidney transplant recipients (KTRs) have not been investigated. Specifically, its impact on blood pressure (BP) and relationship with N-terminal fragment of prohormone B-type natriuretic peptide (NT-proBNP) are unknown. The objectives of this study were to establish the prevalence of hypervolemia among clinically stable KTRs, investigate the predictors of posttransplant hypervolemia, assess its impact on blood pressure, and determine its relationship with NT-proBNP. Methods This single-center cross-sectional study enrolled 123 clinically stable KTRs. Extracellular volume status was determined by multifrequency bioimpedance analysis. Mild and severe hypervolemia were defined as percentage volume expansion of greater than 7% and greater than 15%, respectively. Systolic BP (SBP) and diastolic BP (DBP) were measured, with mean arterial pressure (MAP) calculated. Serum NT-proBNP was quantified using a noncompetitive immunoluminometric assay. Potential demographic, nutritional, and clinical predictors of extracellular volume status, BP, and NT-proBNP levels were assessed. Results Hypervolemia was present in 30% of KTRs, with 5% classified as severe hypervolemia. Significant predictors of volume expansion were increased sodium intake, advancing age, and reduced fat mass (P<0.01 for all associations). Hypervolemia was the only independent predictor of elevated MAP, SBP, and DBP (P<0.001 for all associations). Raised NT-proBNP levels were independently associated with both hypervolemia (P=0.01) and allograft dysfunction (P=0.03). Conclusions Hypervolemia is unexpectedly common among clinically stable KTRs. It is closely associated with elevated BP. The relationship with increased sodium intake signals potential therapeutic focus. Further study is warranted to prospectively investigate objective measures of extracellular volume status among KTRs.

The role of hepcidin-25 in kidney transplantation

Background Hepcidin-25 is a peptide hormone involved in iron absorption and homeostasis and found at increased serum levels in conditions involving systemic inflammation, renal dysfunction, and increased adiposity. Hepcidin may play a role in the pathogenesis of anemia, but its role in kidney transplantation is undefined. Methods This study enrolled 100 stable patients beyond 12 months after transplantation, from a large single United Kingdom center. Serum hepcidin-25 level, and relevant demographic and laboratory data pertinent to posttransplantation anemia, were measured and collected. Independent predictors of serum hepcidin were evaluated, and the relationship between hepcidin and hemoglobin, assessed. Results Independent associations were seen between higher hepcidin levels and allograft dysfunction (estimated glomerular filtration rate), increased inflammation (high-sensitivity C-reactive peptide), higher transferrin saturation (a marker of iron stores), and the use of marrow-suppressive medication (P<0.05 for all). Higher fat tissue index (whole-body multifrequency bioimpedance measurement) was also associated with higher hepcidin levels, but this relationship did not persist after adjustment for inflammation (high-sensitivity C-reactive peptide). In turn, inflammation was associated with increased fat tissue index (P=0.01) and male gender (P=0.04). A nonlinear association between serum hepcidin level and hemoglobin was seen, with a progressive fall in hemoglobin as hepcidin levels rose to 100 ng/mL, but little effect thereafter (P=0.009). This association was independent of renal dysfunction and female gender, both of which were also independently associated with a lower hemoglobin level. Conclusions These results highlight possible mechanisms of hemoglobin reduction in kidney transplantation patients, and the therapeutic opportunities from understanding the role of hepcidin in this context.

The Mechanisms of Physical Fatigue in Kidney Transplant Recipients.: Abstract# D2721

D2721 The Mechanisms of Physical Fatigue in Kidney Transplant Recipients. W. Chan,1,2 D. Jones,2 J. Bosch,2 N. Crabtree,1 O. Kaur,1 A. McClean,1,2 L. Harper,1,2 A. Phillips,2 R. Borrows.1,2 1Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom; 2University of Birmingham, Birmingham, United Kingdom. PURPOSE The mechanisms of physical fatigue in kidney transplant recipients (KTRs) remained unexplored. The primary objectives were to determine the prevalence of physical fatigue in KTRs; assess its impact on quality of life (QoL); and identify the mechanisms of physical fatigue through examinations of cardiorespiratory function (VO2max), perceived exertion, as well as muscle mass, function and conditioning. The secondary objective was to investigate the predictors of raised perceived exertion, a determinant of physical fatigue in KTRs. METHODS This single-centre cross-sectional study enrolled 55 KTRs ≥1 year posttransplantation. Mean age=46±14 years; 58% male. Physical fatigue was measured by multi-dimensional fatigue inventory-20. QoL was assessed with SF-36. VO2max was estimated by sub-maximal exercise test. Rating of perceived exertion (RPE) was determined by age-adjusted Borg-ratings during exercise, with RPE index calculated. Lean body mass (LBM) was quantifi ed with dual energy x-ray absorptiometry. Muscle function was assessed by jumping mechanography (single 2-legged jump [S2LJ] and chair rise test [CRT]). Muscle conditioning was determined by changes in myokine (serum IL-6) levels, taken at rest (Trest), immediately (Timmediate) and 1-hour (T1-hour) after exercise. Demographic, clinical, psychosocial and behavioural predictors of perceived exertion were assessed. RESULTS Physical fatigue was found in 22% of KTRs, and exerted a negative impact on QoL (p<0.001). Median RPE index=1.2 (0.8-2.0). Mean values of VO2max=26.7±9.0 ml/ kg/min; LBM=50.7±11.5 kg; muscle function measured by S2LJ=4045±1136 W, and CRT=1118±268 W. No signifi cant changes of serum IL-6 levels were detected between Trest, Timmediate, and T1-hour. Independent predictors of physical fatigue were reduced VO2max in male (p=0.04) and increased perceived exertion in female (p=0.003). Independent predictors of raised perception were mental fatigue (p=0.03), anxiety (p=0.01), new-onset diabetes after transplantation (p=0.04), absence of cyclosporine (p=0.03), and low alcohol intake (p=0.03). CONCLUSION Physical fatigue in KTRs is driven by reduced VO2max in male, and increased perception in female. Predictors of raised perception were identifi ed, paving the way for future interventional studies. Further research is needed to identify causes of reduced VO2max in KTRs. Abstract# D2722 Cardiorespiratory Fitness in Kidney Transplant Recipients. W. Chan,1,2 D. Jones,2 A. Phillips,2 J. Bosch,2 O. Kaur,1 A. McClean,1,2 L. Harper,1,2 R. Borrows.1,2 1Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom; 2University of Birmingham, Birmingham, United Kingdom. PURPOSE Cardiorespiratory fi tness (VO2max) garners little attention in kidney transplant recipients (KTRs). The primary objectives were to establish the prevalence, impact and predictors of reduced VO2max. The role of VO2max assessment in potential KTRs remains controversial. The secondary objective was to evaluate the prognostic value of pre-transplant cardiorespiratory exercise test. METHODS Primary objectives were tested by a cross-sectional cohort of KTRs ≥1 year posttransplantation (n=55; mean age=46±14 years; 58% male). Secondary objectives were tested by a longitudinal cohort of living-donor KTRs within 1 month pretransplantation (n=26; mean age=41±16 years; 58% male). VO2max was estimated by submaximal exercise test. “Reduced” (≤0.81 predicted) and “severely reduced” (<0.62 predicted) VO2max were delineated. QoL was assessed with SF-36. Clinical outcome data were retrieved from medical records. Demographic, nutritional and clinical predictors of VO2max were assessed. RESULTS Mean KTRs’ VO2max=26.7±9.0 ml/kg/min. “Reduced VO2max” was found in 58% of KTRs, with 22% being “severely reduced”. Post-transplant VO2max positively correlated with QoL (p<0.001), but did not predict 2-year hospitalisation rates and days to fi rst hospitalisation. Predictors of reduced VO2max were female (p=0.004), increased fat mass (p=0.002), hypovolemia (p<0.001), and hypervolemia (p<0.001). In patients awaiting kidney transplantation, pre-transplant VO2max did not correlate with QoL up to 1 year post-transplantation, and did not predict 2-year hospitalisation rates and days to fi rst hospitalisation post-transplantation. Similarly, pre-transplant VO2max did not predict early clinical outcomes within the 1st week post-transplantation including systolic and diastolic blood pressure, lowest standardised early warning score, creatinine reduction ratio, and length of hospital stay. No patient required dialysis, inotropes, and ICU admission within the 1st week post-transplantation. There was no incidence of delayed graft function. CONCLUSION Reduced cardiorespiratory fi tness is common in KTRs, and is associated with reduced QoL. This study identifi ed potential modifi able predictors, setting the scene for interventional studies. The limited predictive value of pre-transplant cardiorespiratory exercise testing on post-transplant QoL and early clinical outcomes needs further validation. D2722 Cardiorespiratory Fitness in Kidney Transplant Recipients. W. Chan,1,2 D. Jones,2 A. Phillips,2 J. Bosch,2 O. Kaur,1 A. McClean,1,2 L. Harper,1,2 R. Borrows.1,2 1Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom; 2University of Birmingham, Birmingham, United Kingdom. PURPOSE Cardiorespiratory fi tness (VO2max) garners little attention in kidney transplant recipients (KTRs). The primary objectives were to establish the prevalence, impact and predictors of reduced VO2max. The role of VO2max assessment in potential KTRs remains controversial. The secondary objective was to evaluate the prognostic value of pre-transplant cardiorespiratory exercise test. METHODS Primary objectives were tested by a cross-sectional cohort of KTRs ≥1 year posttransplantation (n=55; mean age=46±14 years; 58% male). Secondary objectives were tested by a longitudinal cohort of living-donor KTRs within 1 month pretransplantation (n=26; mean age=41±16 years; 58% male). VO2max was estimated by submaximal exercise test. “Reduced” (≤0.81 predicted) and “severely reduced” (<0.62 predicted) VO2max were delineated. QoL was assessed with SF-36. Clinical outcome data were retrieved from medical records. Demographic, nutritional and clinical predictors of VO2max were assessed. RESULTS Mean KTRs’ VO2max=26.7±9.0 ml/kg/min. “Reduced VO2max” was found in 58% of KTRs, with 22% being “severely reduced”. Post-transplant VO2max positively correlated with QoL (p<0.001), but did not predict 2-year hospitalisation rates and days to fi rst hospitalisation. Predictors of reduced VO2max were female (p=0.004), increased fat mass (p=0.002), hypovolemia (p<0.001), and hypervolemia (p<0.001). In patients awaiting kidney transplantation, pre-transplant VO2max did not correlate with QoL up to 1 year post-transplantation, and did not predict 2-year hospitalisation rates and days to fi rst hospitalisation post-transplantation. Similarly, pre-transplant VO2max did not predict early clinical outcomes within the 1st week post-transplantation including systolic and diastolic blood pressure, lowest standardised early warning score, creatinine reduction ratio, and length of hospital stay. No patient required dialysis, inotropes, and ICU admission within the 1st week post-transplantation. There was no incidence of delayed graft function. CONCLUSION Reduced cardiorespiratory fi tness is common in KTRs, and is associated with reduced QoL. This study identifi ed potential modifi able predictors, setting the scene for interventional studies. The limited predictive value of pre-transplant cardiorespiratory exercise testing on post-transplant QoL and early clinical outcomes needs further validation. Abstract# D2723 Changes in Functional Outcomes After an Inpatient Rehabilitation Program for Solid Organ Transplant Recipients. T. Janaudis-Ferreira,1,2 B. Cheung,1 K. Uy,1 J. Chawla,1 S. Mathur,2 J. Patcai.1 1St John’s Rehab Program, Sunnybrook Research Institute, Toronto, ON, Canada; 2Department of Physical Therapy, University of Toronto, Toronto, ON, Canada. Purpose: To describe the changes in functional outcomes after an inpatient rehabilitation program for solid organ transplant (SOT) recipients and determine whether any changes in functional mobility, lower body strength and lower limb muscle strength were associated with changes in functional exercise capacity. Methods: Twenty-one SOT recipients (7 liver; 2 liver + kidney; 1 kidney + pancreas; 2 heart; 2 single lung; 7 double lung; 58±8 yrs; 62% men (n = 13)) were enrolled in the study and participated in a multidisciplinary program (total duration: 23 ± 9 days) that was comprised of occupational therapy, physical therapy, psychological and nutritional support and nursing. Functional exercise capacity (2 Minute Walk test (2MWT)), balance (Berg Balance Scale (BBS)), functional mobility (Time Up and Go (TUG)), lower body strength (30 Second Sit-To-Stand Test), functional independence (Functional Independence Measure (FIM®)), self-reported performance during activities of daily living (ADL) (Canadian Occupational Performance Measure (COPM)) and health related quality of life (Rand-36) were measured before and after the rehabilitation program. Elbow fl exion and knee extension force were measured using a hand-held dynamometer. Results: Sixteen subjects completed the study and showed signifi cant improvements D2723 Changes in Functional Outcomes After an Inpatient Rehabilitation Program for Solid Organ Transplant Recipients. T. Janaudis-Ferreira,1,2 B. Cheung,1 K. Uy,1 J. Chawla,1 S. Mathur,2 J. Patcai.1 1St John’s Rehab Pr