Exercise in Patients on Dialysis: A Multicenter, Randomized Clinical Trial.

Previous studies have suggested the benefits of physical exercise for patients on dialysis. We conducted the Exercise Introduction to Enhance Performance in Dialysis trial, a 6-month randomized, multicenter trial to test whether a simple, personalized walking exercise program at home, managed by dialysis staff, improves functional status in adult patients on dialysis. The main study outcomes included change in physical performance at 6 months, assessed by the 6-minute walking test and the five times sit-to-stand test, and in quality of life, assessed by the Kidney Disease Quality of Life Short Form (KDQOL-SF) questionnaire. We randomized 296 patients to normal physical activity (control; n=145) or walking exercise (n=151); 227 patients (exercise n=104; control n=123) repeated the 6-month evaluations. The distance covered during the 6-minute walking test improved in the exercise group (mean distance±SD: baseline, 328±96 m; 6 months, 367±113 m) but not in the control group (baseline, 321±107 m; 6 months, 324±116 m; P<0.001 between groups). Similarly, the five times sit-to-stand test time improved in the exercise group (mean time±SD: baseline, 20.5±6.0 seconds; 6 months, 18.2±5.7 seconds) but not in the control group (baseline, 20.9±5.8 seconds; 6 months, 20.2±6.4 seconds; P=0.001 between groups). The cognitive function score (P=0.04) and quality of social interaction score (P=0.01) in the kidney disease component of the KDQOL-SF improved significantly in the exercise arm compared with the control arm. Hence, a simple, personalized, home-based, low-intensity exercise program managed by dialysis staff may improve physical performance and quality of life in patients on dialysis.

The role of deconditioning in the end-stage renal disease myopathy: physical exercise improves altered resting muscle oxygen consumption.

BACKGROUND: Skeletal muscle dysfunction and poor exercise tolerance are hallmarks of end-stage renal disease (ESRD). Noninvasively measured (near-infrared spectroscopy, NIRS) resting muscle oxygen consumption (rmVO2) is a biomarker of muscle dysfunction, which can be applied to study the severity and the reversibility of ESRD myopathy. We tested the hypothesis that deconditioning is a relevant factor in ESRD myopathy. METHODS: The whole dialysis population (n = 59) of two of the eight centers participating into the EXCITE study (ClinicalTrials.gov NCT01255969), a randomized trial evaluating the effect of a home-based exercise program on the functional capacity of these patients was studied. Thirty-one patients were in the active arm (exercise group) and 28 in the control arm (no intervention). Normative data for rmVO2 were obtained from a group of 19 healthy subjects. RESULTS: rmVO2 was twice higher (p < 0.001) in ESRDs patients (0.083 ± 0.034 ml/100 g/min) than in healthy subjects (0.041 ± 0.020 ml/100 g/min) indicating substantial skeletal muscle dysfunction in ESRD. rmVO2 correlated with resting heart rate (r = 0.34, p = 0.009) but was independent of age, dialysis vintage, biochemical, vascular and nutrition parameters. After the 6-month exercise program, rmVO2 reduced to 0.064 ± 0.024 ml/100 g/min (-23%, p < 0.001) in the exercise group indicating that skeletal muscle dysfunction is largely reversible but remained identical in the control group (0.082 ± 0.032 to 0.082 ± 0.031 ml/100 g/min). CONCLUSION: Deconditioning has a major role in ESRD myopathy. rmVO2 is a marker of physical deconditioning and has the potential for monitoring re-conditioning programs based on physical exercise in the ESRD population.

A clinical stratification tool for chronic kidney disease progression rate based on classification tree analysis.

BACKGROUND: Registry-based studies have identified risk factors for chronic kidney disease (CKD) and for progression to end-stage renal disease. However, usually, these studies do not incorporate sequential measurements of kidney function and provide little information on the prognosis of individual patients. The aim of this study is to identify which combinations of demographic and clinical characteristics are useful to discriminate patients with a differential annual decline in glomerular filtration rate (GFR). METHODS: This observational retrospective study includes patients enlisted in the registry of the Prevention of Progressive Renal Insufficiency Project of Emilia-Romagna region (Italy) from July 2004 to June 2010, with at least four serum creatinine measurements. Classification tree analysis (CTA) was used to identify subgroups of patients with a different annual GFR decline using demographic and laboratory data collected at study entry. RESULTS: The CTA procedure generated seven mutually exclusive groups. Among patients with proteinuria, those with a baseline estimated GFR (eGFR) of >33 mL/min/1.73 m(2) exhibited the fastest illness progression in the study population (-3.655 mL/min/1.73 m(2)), followed by patients with a baseline eGFR of <33 mL/min/1.73 m(2) and a baseline serum phosphorus of >4.3 mg/dL (-2.833 mL/min/1.73 m(2)). Among patients without proteinuria, those aged <67 years exhibited a significantly faster progression, which was even faster for the subgroup with diabetes. Among patients aged >67 years, females had on average a stable eGFR over time, with a large variability. CONCLUSIONS: It is possible to rely on a few variables typically accessible in routine clinical practice to stratify patients with a different CKD progression rate. Stratification can be used to guide decisions about the follow-up schedule, treatments to slow progression of kidney disease, prevent its complications and to begin planning for dialysis and transplantation.

Fitness for entering a simple exercise program and mortality: a study corollary to the exercise introduction to enhance performance in dialysis (EXCITE) trial.

BACKGROUND/AIMS: In this corollary analysis of the EXCITE study, we looked at possible differences in baseline risk factors and mortality between subjects excluded from the trial because non-eligible (n=216) or because eligible but refusing to participate (n=116). METHODS: Baseline characteristics and mortality data were recorded. Survival and independent predictors of mortality were assessed by Kaplan-Meier and Cox regression analyses. RESULTS: The incidence rate of mortality was higher in non-eligible vs. eligible non-randomized patients (21.0 vs. 10.9 deaths/100 persons-year; P<0.001). The crude excess risk of death in non-eligible patients (HR 1.96; 95% CI 1.36 to 2.77; P<0.001) was reduced after adjustment for risk factors which differed in the two cohorts including age, blood pressure, phosphate, CRP, smoking, diabetes, triglycerides, cardiovascular comorbidities and history of neoplasia (HR 1.60; 95% CI 1.10 to 2.35; P=0.017) and almost nullified after including in the same model also information on deambulation impairment (HR 1.16; 95% CI 0.75 to 1.80; P=0.513). CONCLUSIONS: Deambulation ability mostly explains the difference in survival rate in non-eligible and eligible non-randomized patients in the EXCITE trial. Extending data analyses and outcome reporting also to subjects not taking part in a trial may be helpful to assess the representability of the study population.

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 population.

Respiratory muscle impairment in dialysis patients: can minimal dose of exercise limit the damage? A Preliminary study in a sample of patients enrolled in the EXCITE trial.

AIM: Skeletal muscle atrophy and dysfunction with associated weakness may involve the respiratory muscles of dialysis patients. We evaluated the effect of moderate-intensity exercise on lung function and respiratory muscle strength. METHODS: Fifty-nine patients (25 F, aged 65 ± 13 years) from two centers participating in the multicenter randomized clinical trial EXerCise Introduction To Enhance Performance in Dialysis (EXCITE) were studied. Subjects were randomized into a prescribed exercise group (E), wherein subjects performed two 10-min walking sessions every second day at an intensity below the self-selected speed, or a control group (C) with usual care. Physical performance was assessed by the 6-min walk test (6MWT). Patient lung function and respiratory muscle strength were evaluated by spirometry and maximal inspiratory pressure (MIP), respectively. RESULTS: Forty-two patients (14 F) completed the study. At baseline, the groups did not differ in any parameters. In total, 7 patients (4 in E; 3 in C) showed an obstructive pattern. The pulmonary function parameters were significantly correlated with 6MWT but not with any biochemical measurements. Group E safely performed the exercise program. At follow-up, the spirometry parameters did not change in either group. A deterioration of MIP (-7 %; p = 0.008) was observed in group C, but not in group E (+3.3 %, p = ns). In E, an increase of 6MWT was also found (+12 vs. 0 % in C; p = 0.038). CONCLUSION: In dialysis patients, a minimal dose of structured exercise improved physical capacity and maintained a stable respiratory muscle function, in contrast to the control group where it worsened.

[Organizational models in the Italian nephrology, dialysis and transplantation network]. / Modelli organizzativi della rete nefrologica, dialitica e trapiantologica Italiana.

In this article, the Italian Society of Nephrology discusses the recent statement of the Italian National Government regarding the 'The definition of the structure and technological standards of hospital health care' and suggests a new model of organization of the Italian Nephrology, Dialysis and Transplantation Network. In particular, the Italian Society of Nephrology proposes the presence of a nephrologist as part of the Emergency Hospital Network, to oversee all extracorporeal replacement treatments taking place in Intensive Care Units. Finally, this article recommends the cooperation of the nephrologist with primary health care teams and general practitioners as a move to prevent the complications of chronic kidney disease, thus improving short-term and long-term survival outcomes and reducing the costs to the National Health System.

Have we new therapeutic strategies in the treatment of renovascular nephropathy?

Renal artery stenosis (RAS) is a cause of hypertension and ischemic nephropathy. The incidence of this disorder is probably less than 1% in patients with mild hypertension, but rises to as high as 10 to 40% in patients with acute, severe or refractory hypertension. Significant RAS can be caused by atheromatous plaques, or due to fibromuscular dysplasia (FMD). Atherosclerotic lesions are present in almost 7% of adults older than 65 years and up to 50% of patients presenting with diffuse atherosclerotic disease. In contrast to atherosclerosis, FMD most often affects women under the age of 50 and typically involves the distal main renal artery or the intrarenal branches. The optimal treatment for RAS is not yet established. Based on recent trials, we reviewed the literature on pharmacological and endovascular treatment of atherosclerotic RAS and ischemic nephropathy.

Nephroangiosclerosis and its pharmacological approach.

Nephroangiosclerosis (NAS) is a major cause of progressive renal insufficiency. Hypertension is very important in the causation of NAS but other factors such as race, age, metabolic variables, and genetics play a pathogenic and prognostic role. A multifactorial treatment strategy, including antihypertensive, lipid-lowering and anti-platelet agents, could improve cardiovascular and renal outcomes in patients with vascular nephropathy.