Naomi Clyne

Twelve weeks of exercise training increases muscle function and walking capacity in elderly predialysis patients and healthy subjects

Muscle function declines with age and progressive uraemia. We examined whether elderly predialysis patients could improve thigh muscle function, walking capacity, and functional mobility to the same extent as elderly healthy subjects when participating in 12 weeks of individual muscle endurance exercises for the thigh as well as in a low-intensive group programme. The uraemic exercise and comparison groups comprised 16 patients (age 76 ± 7 years, glomerular filtration rate 18 ± 5 ml/min) and 9 patients (age 72 ± 6 years, glomerular filtration rate 16 ± 5 ml/min), respectively. The healthy exercise and comparison groups comprised 18 subjects (age 75 ± 7 years) and 5 subjects (age 79 ± 4 years), respectively. Muscular strength, dynamic endurance, walking capacity, and functional mobility increased significantly in both the uraemic and the healthy exercise groups after 12 weeks of regular muscle endurance exercise training, whereas there was no significant change in static muscle endurance and quality of life in either group. None of the values changed for the uraemic comparison group nor the healthy comparison group during the observation period. Elderly predialysis patients had lower muscle function and mobility as compared with elderly healthy subjects, but were able to improve both after 12 weeks of exercise training to the same extent as elderly healthy subjects.

Left Ventricular Geometry Predicts Cardiovascular Outcomes Associated with Anemia Correction in CKD

Partial correction of anemia in patients with chronic kidney disease (CKD) reduces left ventricular hypertrophy (LVH), which is a risk factor for cardiovascular (CV) morbidity, but complete correction of anemia does not improve CV outcomes. Whether LV geometry associates with CV events in patients who are treated to different hemoglobin (Hb) targets is unknown. One of the larger trials to study the effects of complete correction of anemia in stages 3 to 4 CKD was the Cardiovascular Risk Reduction by Early Anemia Treatment with Epoetin Beta (CREATE) trial. Here, we analyzed echocardiographic data from CREATE to determine the prevalence, dynamics, and prognostic implications of abnormal LV geometry in patients who were treated to different Hb targets. The prevalence of LVH at baseline was 47%, with eccentric LVH more frequent than concentric. During the study, LVH prevalence and mean left ventricular mass index did not change significantly, but LV geometry fluctuated considerably within 2 yr in both groups. CV event-free survival was significantly worse in the presence of concentric LVH and eccentric LVH compared with the absence of LVH (P = 0.0009 and P < or = 0.0001, respectively). Treatment to the higher Hb target associated with reduced event-free survival in the subgroup with eccentric LVH at baseline (P = 0.034). In conclusion, LVH is common and associates with poor outcomes among patients with stages 3 to 4 CKD, although both progression and regression of abnormal LV geometry occur. Complete anemia correction may aggravate the adverse prognosis of eccentric LVH.

Effects of exercise training in predialytic uremic patients

We examined the effects of physical training in 10 predialytic uremic patients (7 men, 3 women, mean age 47 +/- 8 years) with an average glomerular filtration (GFR) of 15 +/- 7 ml/min x 1.73 m2. All 10 patients participated in an exercise programme 3 times/week for 3 months and were compared to a control group of 9 patients with comparable baseline variables. The exercise group increased its maximal exercise capacity measured by standardized exercise test on a bicycle ergometer, from an average 159 +/- 49 to 174 +/- 57 W (p less than 0.01). They also showed a decrease in heart rate at equal load (138 +/- 29-123 +/- 18 beats/min, p less than 0.05). The control group did not change its exercise capacity (171 +/- 60 and 171 +/- 65 W, respectively, NS), nor its heart rate at equal load (124 +/- 24 and 123 +/- 24 beats/min, respectively, NS). Thigh muscular function assessed by static endurance increased from a median 77 s (range 27-197) to 113 s (range 66-201), p less than 0.002. Dynamic muscular endurance increased from a median number of 41 movements (range 28-105) to 93 movements (range 45-139), p less than 0.001. The corresponding figures for the controls were: static endurance 60 (range 20-209) and 47 s (range 9-203), respectively, NS; dynamic endurance 53 (range 19-190) and 43 movements (range 10-126), respectively, NS. Total hemoglobin, blood volume, GFR, blood pressure and echocardiographic variables remained unchanged during the observation period. We conclude that in predialytic uremic patients, physical training improves exercise capacity mainly due to an improved muscular function.

Effect of erythropoietin treatment on physical exercise capacity and on renal function in predialytic uremic patients

Anemia is already present in patients with moderate renal failure and is a major cause of the decline in exercise capacity seen in these patients. We examined the effects of erythropoietin (EPO) treatment in 12 predialytic uremic patients (EPO group: mean age 46 +/- 12 years; 6 men, 6 women) with a mean glomerular filtration rate (GFR) of 10 +/- 4 ml/min x 1.73 m2. These patients were compared to a control group of 8 patients (5 men, 3 women). The observation period was 3 months. The EPO group received 300 U/kg body weight i.v. once a week. The EPO group increased their total hemoglobin (THb) from 323 +/- 89 to 466 +/- 128 g (p less than 0.001) and their hemoglobin concentration from 86 +/- 8 to 117 +/- 11 milligrams (p less than 0.001). Their exercise capacity, measured by a standardized exercise test on a bicycle ergometer, increased from 128 +/- 45 to 147 +/- 57 W (p less than 0.01). The control group did not change their THb (349 +/- 124 and 357 +/- 131 g), hemoglobin (93 +/- 8 and 94 +/- 10 milligrams) or exercise capacity (98 +/- 49 and 101 +/- 50 W) during the observation period. There was a significant correlation between the increase in THb and the increase in exercise capacity in the EPO group (r = 0.81, p less than 0.005). The GFR was unchanged in both groups (EPO group: 10 +/- 4 and 10 +/- 6 ml/min x 1.73 m2; control group: 8 +/- 3 and 8 +/- 3 ml/min x 1.73 m2).(ABSTRACT TRUNCATED AT 250 WORDS)

Occurrence and significance of heart disease in uraemia : An autopsy study

The occurrence of heart disease in uraemic patients was evaluated from study of 94 autopsied cases of chronic renal failure. The most common autopsy-ascertained causes of death were congestive heart failure (37%), acute myocardial infarction (13%) and tamponading pericarditis (8%). Death from congestive heart failure was significantly more common among the patients aged 60 or more than in the younger group. Hypertension was recorded in 59% of the patients, including all those with fatal myocardial infarction. Coronary arteriosclerosis was graded as absent to mild in about 40% of the patients. More severe grades occurred predominantly in the older patients. Tamponading pericarditis almost exclusively affected patients in haemodialysis. The authors conclude that most deaths among patients with end-stage renal failure were due to congestive heart failure. Ischaemic heart disease did not seem to be a more common cause of death than in the general population.

Progressive decline in renal function induces a gradual decrease in total hemoglobin and exercise capacity

We examined 58 patients (38 men, 20 women; mean age: 45 +/- 12 years; body mass index: 24 +/- 4 kg/m2) with a glomerular filtration rate (GFR) ranging from 3 to 32 ml/min, in order to determine the effects of a progressive decline in renal function on total hemoglobin (THb) and exercise capacity. The THb ranged from 185 to 759 g and the hemoglobin concentration ranged from 66 to 151 g/l. Maximal exercise capacity ranged from 50 to 260 W (40-143% of the expected norm). Nearly all the patients interrupted their exercise tests due to general fatigue, leg tiredness or a combination of these factors. There was a significant partial correlation between THb and GFR after sex and age had been accounted for (r = 0.39; p < 0.005). Maximal exercise capacity and THb showed a significant partial correlation after sex, age and GFR had been accounted for (r = 0.27; p < 0.05). Maximal exercise capacity showed a significant partial correlation with GFR after sex, age and THb had been accounted for (r = 0.30; P < 0.05). In conclusion, there is a gradual decline in THb and maximal exercise capacity as uremia progresses. Anemia appears to be a contributory cause responsible for the decrease in maximal exercise capacity along with other factors pertinent to uremia per se.

Effects of regular resistance training on muscle histopathology and morphometry in elderly patients with chronic kidney disease.

Heiwe S, Clyne N, Tollbäck A, Borg K: Effects of regular resistance training on muscle histopathology and morphometry in elderly patients with chronic kidney disease. Am J Phys Med Rehabil 2005;84:865–874. Objective:To evaluate muscle histopathological outcomes, adaptation in muscle fiber area, and fiber type proportion after a resistance training program for patients with chronic kidney disease. Design:Vastus lateralis muscle biopsies before and after the study period in seven patients and six healthy subjects performing the exercise program and in five patients in a nonexercising comparison group. Results:The change in degree of histopathological abnormality did not differ between the groups after the exercise program. Muscle fiber type proportion and muscle fiber area was also the same after the observation period. Conclusions:Patients with chronic kidney disease have muscle histopathological abnormalities already in the predialysis phase. There was no indication that the exercise program had disadvantageous effects on muscle histopathology in these patients. There were no differences in muscle fiber area or in fiber type proportion after the exercise program within or between the groups. Thus, a workload of 60% of one repetition maximum was sufficient to increase muscular strength and endurance in patients with chronic kidney disease but not to increase muscle fiber area or to change muscle fiber type proportion.

Physical working capacity in uremic patients

By the time patients have reached end-stage renal failure and need dialysis, a majority are experiencing debilitating fatigue and lack of energy. Few dialysis patients are gainfully employed and many are unable to care for themselves. The pervasive feeling of fatigue among uremic patients, in conjunction with the growing proportion of elderly and very old patients on dialysis, makes it necessary for nephrologists to focus their attention on which factors actually are responsible for rendering their patients dysfunctional in their everyday lives.Predialysis patients have a reduced physical exercise capacity compared to the expected norm, with further deterioration as uremia progresses (7, Fig. 1). Subsequently, when these patients reach end-stage renal failure and need dialysis their exercise capacity is only 40-60% of the expected norm (26). The cause of this physical deterioration is multifactorial. Glomerular filtration rate (GFR) is one important determinant for maximal exercise capacity in the predial...

The effect of parathyroidectomy on patient survival in secondary hyperparathyroidism

BACKGROUND Secondary hyperparathyroidism is a common condition in patients with end-stage renal disease and is associated with osteoporosis and cardiovascular disease. Despite improved medical treatment, parathyroidectomy (PTX) is still necessary for many patients on renal replacement therapy. The aim of this study was to evaluate the effect of PTX on patient survival. METHODS A nested index-referent study was performed within the Swedish Renal Registry (SRR). Patients on maintenance dialysis and transplantation at the time of PTX were analysed separately. The PTX patients in each of these strata were matched for age, sex and underlying renal diseases with up to five referent patients who had not undergone PTX. To calculate survival time and hazard ratios, indexes and referents were assigned the calendar date (d) of the PTX of the index patient. The risk of death after PTX was calculated using crude and adjusted Cox proportional hazards regressions. RESULTS There were 20 056 patients in the SRR between 1991 and 2009. Of these, 579 (423 on dialysis and 156 with a renal transplant at d) incident patients with PTX were matched with 1234/892 non-PTX patients. The adjusted relative risk of death was a hazard ratio (HR) of 0.80 [95% confidence interval (CI) 0.65-0.99] for dialysis patients at d who had undergone PTX compared with matched patients who had not. Corresponding results for the patients with a renal allograft at d were an HR of 1.10 (95% CI 0.71-1.70). CONCLUSIONS PTX was associated with improved survival in patients on maintenance dialysis but not in patients with renal allograft.

Effects of Renal Failure on Skeletal Muscle

In this cross-sectional study, we examined biopsies from the vastus lateralis muscle of 13 predialytic uremic men (mean age 46 +/- 8 years). Their average glomerular filtration rate was 14 +/- 7 ml/min x 1.73 m2 and their maximal exercise capacity, measured by standardized exercise test on a bicycle ergometer, was 184 +/- 45 W (94% of the expected norm). The proportion of type I fibers (type I%) in the uremic group was similar to that of the reference group (42 +/- 11 vs. 41 +/- 8% NS). The proportion of type IIA fibers (type IIA%) in the uremic group was higher than in the reference group (44 +/- 10 compared to 35 +/- 9%, p < 0.05). The proportion of type IIB fibers (type IIB%) was lower than in the reference group (13 +/- 8 vs. 21 +/- 8%, p < 0.05). Type I fiber area was similar to that of the reference group (4,768 +/- 1,033 vs. 4,627 +/- 1,112 microns 2, NS). Type IIA and type IIB fiber areas tended to be smaller than those of the reference group (type IIA fiber area: 4,515 +/- 929 vs. 5,213 +/- 1,288 microns 2, NS; type IIB fiber area: 3,953 +/- 1,066 vs. 4,406 +/- 1,582 microns 2, NS) with a type IIA area/type I area ratio which was significantly lower than in the reference group. Citrate synthase activity was 0.48 +/- 0.08 mu kat/g in the uremic group and 0.50 +/- 0.08 mu kat/g in the reference group, NS.(ABSTRACT TRUNCATED AT 250 WORDS)