Influence of acute moderate- to high-intensity aerobic exercise on markers of immune function and microparticles in renal transplant recipients.

Renal transplant recipients (RTRs) and patients with nondialysis chronic kidney disease display elevated circulating microparticle (MP) counts, while RTRs display immunosuppression-induced infection susceptibility. The impact of aerobic exercise on circulating immune cells and MPs is unknown in RTRs. Fifteen RTRs [age: 52.8 ± 14.5 yr, estimated glomerular filtration rate (eGFR): 51.7 ± 19.8 mL·min-1·1.73 m-2 (mean ± SD)] and 16 patients with nondialysis chronic kidney disease (age: 54.8 ± 16.3 yr, eGFR: 61.9 ± 21.0 mL·min-1·1.73 m-2, acting as a uremic control group), and 16 healthy control participants (age: 52.2 ± 16.2 yr, eGFR: 85.6 ± 6.1 mL·min-1·1.73 m-2) completed 20 min of walking at 60-70% peak O2 consumption. Venous blood samples were taken preexercise, postexercise, and 1 h postexercise. Leukocytes and MPs were assessed using flow cytometry. Exercise increased classical (P = 0.001) and nonclassical (P = 0.002) monocyte subset proportions but decreased the intermediate subset (P < 0.001) in all groups. Exercise also decreased the percentage of platelet-derived MPs that expressed tissue factor in all groups (P = 0.01), although no other exercise-dependent effects were observed. The exercise-induced reduction in intermediate monocyte percentage suggests an anti-inflammatory effect, although this requires further investigation. The reduction in the percentage of tissue factor-positive platelet-derived MPs suggests reduced prothrombotic potential, although further functional assays are required. Exercise did not cause aberrant immune cell activation, suggesting its safety from an immunological standpoint (ISRCTN38935454).

Identification of the most clinically useful skeletal muscle mass indices pertinent to sarcopenia and physical performance in chronic kidney disease.

AIM: Patients with chronic kidney disease (CKD) are characterised by low skeletal muscle mass that negatively impacts physical performance. Operational definitions of 'low muscle mass' are inconsistent, and it is unknown how different skeletal muscle mass indices affect the relationship between muscle mass and physical function. METHODS: Appendicular skeletal muscle mass (ASM) was measured by dual-energy X-ray absorptiometry in 72 CKD patients. Along with crude ASM, alternative muscle indices were calculated adjusting for height, height-squared, body mass, and BMI. Physical performance was assessed by handgrip strength, sit-to-stand tests, gait speed, the incremental shuttle walk test and 'Short Physical Performance Battery'. RESULTS: Prevalence of 'low muscle mass' ranged from 26% to 35% of patients depending on the criteria used. The relationship between muscle mass indices and physical function differed for each criteria. Using average coefficients, the association with overall physical function and muscle indices were as follows: crude ASM (r = .258), ASM/height (r = .249), ASM/height-squared (r = .332), ASM/body mass (r = .249) and ASM/BMI (r = .206). Muscle adjusted for markers of adiposity (ASM/body fat %, r = .266; ASM/fat mass, r = .338) provided the best overall associations with physical function. CONCLUSION: The use of alternative muscle mass indices provide different estimates of 'low muscle mass' prevalence, and the strongest (and most useful definition in regard to functional status) involves adjustment for either total or relative body fat. ASM adjusted for adiposity may be physiologically and clinically more relevant in patients with renal disease.

Anthropometry-based Equations to Estimate Body Composition: A Suitable Alternative in Renal Transplant Recipients and Patients With Nondialysis Dependent Kidney Disease?

OBJECTIVE: Chronic kidney disease (CKD) patients and renal transplant recipients (RTRs) are characterized by aberrant body composition such as muscle wasting and obesity. It is still unknown which is the most accurate method to estimate body composition in CKD. We investigated the validity of the Hume equation and bioelectrical impedance analysis (BIA) as an estimate of body composition against dual-energy X-ray absorptiometry (DXA) in a cohort of nondialysis dependent (NDD)-CKD and RTRs. DESIGN AND METHODS: This was a cross-sectional study with agreement analysis of different assessments of body composition conducted in 61 patients (35 RTRs and 26 NDD-CKD) in a secondary care hospital setting in the UK. Body composition (lean mass [LM], fat mass [FM], and body fat% [BF%]) was assessed using multifrequency BIA and DXA, and estimated using the Hume formula. Method agreement was assessed by intraclass correlation coefficient (ICC), regression, and plotted by Bland and Altman analysis. RESULTS: Both BIA and the Hume formula were able to accurately estimate body composition against DXA. In both groups, the BIA overestimated LM (1.7-2.1 kg, ICC .980-.984) and underestimated FM (1.3-2.1 kg, ICC .967-.972) and BF% (3.1-3.8%, ICC .927-.954). The Hume formula also overestimated LM (3.5-3.6 kg, ICC .950-.960) and underestimated BF% (1.9-2.1%, ICC .808-.859). Hume-derived FM was almost identical to DXA in both groups (-0.3 to 0.1 kg, ICC .947-.960). CONCLUSION: Our results demonstrate, in RTR and NDD-CKD patients, that the Hume formula, whose estimation of body composition is based only upon height, body mass, age, and sex, may reliably predict the same parameters obtained by DXA. In addition, BIA also provided similar estimates versus DXA. Thus, the Hume formula and BIA could provide simple and inexpensive means to estimate body composition in renal disease.

Are Outcomes of Acute Meniscus Root Tear Repair Better Than Debridement or Nonoperative Management? A Systematic Review.

BACKGROUND: Meniscus root tears (MRTs) are defined as radial tears within 1 cm of the meniscus root insertion or an avulsion of the meniscus root itself. They lead to altered joint loading because of the failure to convert axial (compressive) loads into hoop stresses. Untreated MRTs can result in altered joint biomechanics and accelerated articular cartilage degeneration and the development of osteoarthritis (OA), yet optimal management remains unclear. PURPOSE: To review treatment outcomes after acute MRTs by surgical repair, debridement, meniscectomy, or nonoperative treatment. DESIGN: Systematic review; Level of evidence, 4. METHODS: A systematic review of the evidence from human clinical studies was conducted with electronic searches of the PUBMED, Medline, EMBASE, and the Cochrane Library databases. One reviewer extracted the data and 2 reviewers assessed the risk of bias and performed synthesis of the evidence. RESULTS: Eleven studies of low to moderate methodological quality were identified. All treatment options improved functional scores after >12 months. Arthroscopic repair may be associated with better functional outcomes when compared with partial meniscectomy and nonoperative management at 12-month follow-up. Radiographic progression of OA occurred in all treatment groups; there was some evidence that this was delayed after repair when compared with other treatments. Baseline severity of meniscal extrusion, varus malalignment, and pretreatment degeneration were predictors of poor functional outcomes. Age was not found to be an independent predictor of functional outcome. CONCLUSION: The current level 3 and 4 evidence suggests that arthroscopic repair may result in slower progression of radiological deterioration compared with meniscectomy and nonoperative management. The current literature does not support the exclusion of patients from MRT repair on the basis of age. Patients undergoing acute MRT treatments (repair, debridement, or nonoperative) can be expected to experience improvement in functional outcomes after >12 months. The strength of conclusions are limited because of the paucity of high-quality studies on this subject. Further studies, preferably randomized sham controlled trials with function-oriented rehabilitation programs, are needed to compare treatment strategies and stratification of care based on the risk of meniscal extrusion. REGISTRATION: CRD42018085092 (PROSPERO).

Effects of Exercise and Sport in Solid Organ Transplant Recipients: A Review.

Solid organ transplantation is the criterion standard treatment for many with end-organ failure and can offer a new independence from the burden of disease. However solid organ transplant recipients (SOTRs) remain at high risk of cardiovascular (CV) disease, and poor quality of life and physical functioning. Increasing physical activity and exercise can improve the health of the general population; however, the effects on those with a transplant remain unclear. Intensive exercise and sporting activity has the potential to be beneficial, although there remain concerns particularly around the effects on immune function and the CV system. This review summarizes what is known about the effects of exercise on determinants of health in SOTRs and then collates the available literature investigating the consequences of intensive exercise and sport on the health of SOTR. There is a paucity of high-quality research, with most evidence being case studies or anecdotal; this is understandable given the relatively few numbers of SOTRs who are performing sport and exercise at a high level. However, if suitable evidence-based guidelines are to be formed and SOTRs are to be given reassurances that their activity levels are not detrimental to their transplanted organ and overall health, then more high-quality studies are required.

Physical activity, immune function and inflammation in kidney patients (the PINK study): a feasibility trial protocol.

INTRODUCTION: Patients with chronic kidney disease (CKD) display increased infection-related mortality and elevated cardiovascular risk only partly attributed to traditional risk factors. Patients with CKD also exhibit a pro-inflammatory environment and impaired immune function. Aerobic exercise has the potential to positively impact these detriments, but is under-researched in this patient population. This feasibility study will investigate the effects of acute aerobic exercise on inflammation and immune function in patients with CKD to inform the design of larger studies intended to ultimately influence current exercise recommendations. METHODS AND ANALYSIS: Patients with CKD, including renal transplant recipients, will visit the laboratory on two occasions, both preceded by appropriate exercise, alcohol and caffeine restrictions. On visit 1, baseline assessments will be completed, comprising anthropometrics, body composition, cardiovascular function and fatigue and leisure time exercise questionnaires. Participants will then undertake an incremental shuttle walk test to estimate predicted peak O2 consumption (VO2peak). On visit 2, participants will complete a 20 min shuttle walk at a constant speed to achieve 85% estimated VO2peak. Blood and saliva samples will be taken before, immediately after and 1 hour after this exercise bout. Muscle O2 saturation will be monitored throughout exercise and recovery. Age and sex-matched non-CKD 'healthy control' participants will complete an identical protocol. Blood and saliva samples will be analysed for markers of inflammation and immune function, using cytometric bead array and flow cytometry techniques. Appropriate statistical tests will be used to analyse the data. ETHICS AND DISSEMINATION: A favourable opinion was granted by the East Midlands-Derby Research Ethics Committee on 18 September 2015 (ref 15/EM/0391), and the study was approved and sponsored by University Hospitals of Leicester Research and Innovation (ref 11444). The study was registered with ISRCTN (ref 38935454). The results will be presented at relevant conferences, and it is anticipated that the reports will be published in appropriate journals in 2018.

Cardiovascular risk factors following renal transplant.

Kidney transplantation is the gold-standard treatment for many patients with end-stage renal disease. Renal transplant recipients (RTRs) remain at an increased risk of fatal and non-fatal cardiovascular (CV) events compared to the general population, although rates are lower than those patients on maintenance haemodialysis. Death with a functioning graft is most commonly due to cardiovascular disease (CVD) and therefore this remains an important therapeutic target to prevent graft failure. Conventional CV risk factors such as diabetes, hypertension and renal dysfunction remain a major influence on CVD in RTRs. However it is now recognised that the morbidity and mortality from CVD are not entirely accounted for by these traditional risk-factors. Immunosuppression medications exert a deleterious effect on many of these well-recognised contributors to CVD and are known to exacerbate the probability of developing diabetes, graft dysfunction and hypertension which can all lead on to CVD. Non-traditional CV risk factors such as inflammation and anaemia have been strongly linked to increased CV events in RTRs and should be considered alongside those which are classified as conventional. This review summarises what is known about risk-factors for CVD in RTRs and how, through identification of those which are modifiable, outcomes can be improved. The overall CV risk in RTRs is likely to be multifactorial and a complex interaction between the multiple traditional and non-traditional factors; further studies are required to determine how these may be modified to enhance survival and quality of life in this unique population.