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

Erythrocyte calpain activity and left ventricular mass in essential hypertension

BACKGROUND: Calpains are cytoplasmic proteases widely distributed among eucaryotic cells. Low levels of calpain activity were found in hypertrophic hearts from hypertensive rats, but its role in hypertrophic hearts from human hypertensives is unknown. Therefore, calpain activity was investigated in erythrocytes from essential hypertensive patients in relation to their left ventricular mass. OBJECTIVE: To study the role of calpain activity in the development of left ventricular hypertrophy (LVH) in human essential hypertension. METHODS: A total of 115 hypertensives (72 untreated and 43 with treatment interrupted for at least 4 months) were included in the study. Calpain I activity was measured in human erythrocytes and LVH was measured as left ventricular mass index (LVMI) by M-mode echocardiography. RESULTS: Values are given as mean+/-SEM. The hypertensives (97 men and 18 women) were 43.5+/-0.9 years old with mild to moderate levels of hypertension (systolic/diastolic blood pressure of 147.9+/-1.4/98.7+/-0.9 mmHg) and relatively recent LVH onset (3.5+/-0.5 years). An inverse relation between LVMI and erythrocytic calpain activity was present in all (P = 0.0023, R2 = 7.9%). This relation was still present considering only untreated hypertensives (P = 0.008; R2 = 9.7%), but was lost in the 43 previously treated hypertensives. Moreover, in the untreated hypertensives, after excluding the possible confounding effects of sex, age, body mass index, blood pressure and duration of hypertension, a stepwise regression showed that only two variables remained significantly related to LVMI: calpain (F = 6.23) and mean arterial pressure (F = 4.689). No relations were found between LVMI and calpastatin activity either in the whole population, or in treated or untreated hypertensives. CONCLUSIONS: If we assume that the level of erythrocyte calpain activity mirrors the level in cardiomyocytes, these data seem to suggest that increased protein degradation by calpain may prevent the development of LVH in hypertensive patients. This effect is independent of the duration and severity of hypertension

Oxidative stress in elderly chronic renal failure patients : effects of renal replacement therapies on cell membrane fluidity

Abstract BACKGROUND: Renal replacement therapies (RRTs) produce a partial loss of antioxidants and formation of reactive oxygen species (ROS), which are a major factor involved in alterations of plasma membrane fluidity and endothelial activation, but their role on plasma membrane fluidity in vivo is still unclear. We compared erythrocyte plasma membrane fluidity, ROS and total plasma antioxidant defenses (Lagtime) in aged patients with chronic renal failure (CRF) on conservative treatment, peritoneal dialysis (PD) and hemodialysis (HD) before (HD-pre) and after (HD-post) a treatment, to evaluate the role of different RRTs on oxidative stress and plasma membrane fluidity in aged patients. METHODS: We assessed erythrocyte plasma membrane fluidity, plasma lipid hydroperoxide levels and Lag-Time in 11 CRF patients on conservative treatment, 15 on PD, 12 on HD and 30 healthy controls. RESULTS: Hydroperoxides were higher in CRF, PD and HD-post, whereas Lag-time was significantly lower in PD, CRF and in HD-post. CRF, PD and HD-pre also had higher membrane fluidity (rsDPH), compared with HD-post and controls. CONCLUSION: These findings are in keeping with the hypothesis that the Lag-time decrease is due not only to the effect of the RRT but also to the uremic state, and that PD patients undergo a chronic, greater oxidative stress. Contrary to expectations, all patients showed greater erythrocyte membrane fluidity, which can be attributed to uremic toxicity. These observations reinforce the hypothesis that oxidative stress is an intrinsic component of this disease state and indeed is already present also in CRF not yet requiring RRT

Erythrocyte calcium influx is related to severity of ventricular arrhythmias in uremic patients

BACKGROUND: Myocardial disorders are a remarkable cause of morbidity and mortality in chronic haemodialysed patients (HD). They could be favoured by alteration of cell Ca(2+) handling. In previous studies we characterized an erythrocyte Ca(2+) influx, sensitive to membrane potential and inhibited by Ca(2+) antagonists. Since its maximal influx rate was decreased in HD patients, this study investigates if Ca(2+) influx alterations are related to myocardial disorders in HD patients. METHODS: Voltage-sensitive erythrocyte Ca(2+) influx was measured in 30 healthy controls and in 53 patients (47 HD patients and six patients with left ventricular hypertrophy and normal kidney function), using fura 2. In 29 HD patients and in six healthy subjects Ca(2+) influx was also determined in the presence of parathyroid hormone (PTH) in vitro. Patients were classified according to Lown's ventricular arrhythmias classification after 24-h Holter electrocardiograph (ECG) monitoring. Forty-six patients underwent echocardiography. RESULTS: Voltage-sensitive erythrocyte Ca(2+) influx was significantly reduced in HD patients. Maximal influx rate was significantly higher in HD patients of Lown's classes 3 and 4 (0.789 +/- 0.156 nmol/s, n = 8; P < 0.01) than in patients of classes 1 and 2 (0.499 +/- 0.055 nmol/s, n=15), or without ventricular arrhythmias (0.400 +/- 0.041 nmol/s, n = 24). Maximal influx rate was directly correlated to left ventricular mass index (LVM) (r = 0.353, P < 0.05). Subjects with left ventricular hypertrophy and normal kidney function displayed erythrocyte Ca(2+) influx similar to that of normal subjects. Multiple regression indicates that LVM and Ca(2+) influx were independently related to severity of arrhythmias. When added to the influx assay, PTH increased the maximal influx rate only in patients with ventricular arrhythmias. CONCLUSION: Myocardial dysfunction and altered ventricular excitability could be related in uraemic HD patients to alterations of calcium transport, as found in the erythrocyte model. Reduced resistance to PTH could contribute to this phenomenon

Acute effect of a peritoneal dialysis exchange on electrolyte concentration and QT interval in uraemic patients

Background: Hemodialysis (HD) sessions induce changes in plasma electrolytes that lead to modifications of QT interval, virtually associated with dangerous arrhythmias. It is not known whether such a phenomenon occurs even during peritoneal dialysis (PD). The aim of the study is to analyze the relationship between dialysate and plasma electrolyte modifications and QT interval during a PD exchange. Methods: In 15 patients, two manual PD 4-h exchanges were performed, using two isotonic solutions with different calcium concentration (Ca++1.25 and Ca1.75++&nbsp;mmol/L). Dialysate and plasma electrolyte concentration and QT interval (ECG Holter recording) were monitored hourly. A computational model simulating the ventricular action potential during the exchange was also performed. Results: Dialysis exchange induced a significant plasma alkalizing effect (p &lt; 0.001). Plasma K+ significantly decreased at the third hour (p &lt; 0.05). Plasma Na+ significantly decreased (p &lt; 0.001), while plasma Ca++ slightly increased only when using the Ca 1.75++&nbsp;mmol/L solution (p &lt; 0.01). The PD exchange did not induce modifications of clinical relevance in the QT interval, while a significant decrease in heart rate (p &lt; 0.001) was observed. The changes in plasma K+ values were significantly inversely correlated to QT interval modifications (p &lt; 0.001), indicating that even small decreases of K+ were consistently paralleled by small QT prolongations. These results were perfectly confirmed by the computational model. Conclusions: The PD exchange guarantees a greater cardiac electrical stability compared to the HD session and should be preferred in patients with a higher arrhythmic risk. Moreover, our study shows that ventricular repolarization is extremely sensitive to plasma K+ changes, also in normal range

High prevalence of vertebral fractures assessed by quantitative morphometry in hemodialysis patients, strongly associated with vascular calcifications

Few studies have provided information on the prevalence of vertebral fractures (VFs) and their risk factors in hemodialysis patients. A multicenter, cross-sectional, observational study was carried out to assess the prevalence of VFs and vascular calcifications (VCs) in 387 hemodialysis patients (mean age 64.2 \ub1 14.1 years, 63 % males) and in a control group of 51 osteoporotic subjects. Biochemical tests included 25(OH) vitamin D, bone Gla protein (total and undercarboxylated), and total matrix Gla protein. Vertebral quantitative morphometry was carried out centrally for the detection of VF, defined as reduction by 6520 % of one of the vertebral body dimensions. In the same radiograph, aortic and iliac VC scores were calculated. Prevalence of VF was 55.3 % in hemodialysis patients and 51.0 % in the control group. Multivariate analysis disclosed that male gender (59.8 vs. 47.6 %, p = 0.02; OR = 1.78, 95 % CI 1.15-2.75) and age (mean \ub1 SD 66.7 \ub1 13.1 vs. 61.0 \ub1 14.7 years, p < 0.001; OR = 1.03, 95 % CI 1.01-1.05) were significantly associated with VF. The prevalence of aortic VC was significantly higher in hemodialysis patients than in controls (80.6 vs. 68.4 %, p = 0.001). The factors with the strongest association with VC, apart from atrial fibrillation, were serum 25(OH)vitamin D levels below 29 ng/mL for aortic VC (OR = 1.85, 95 % CI 1.04-3.29) and VF both for aortic (OR = 1.77, 95 % CI 1.00-3.14) and iliac (OR = 1.96, 95 % CI 1.27-3.04) VC. In conclusion, the prevalence of VF, especially in males, and VC, in both genders, is high in hemodialysis patients. VF is associated with VC. Vitamin D deficiency is also associated with VC. Further longitudinal studies are warranted to investigate fractures in renal patients. \ua9 2013 Springer Science+Business Media New York

PERITONEAL ULTRAFILTRATION IN REFRACTORY HEART FAILURE: A COHORT STUDY

Introduction: Acutely decompensated heart failure (HF) in patients with diuretic resistance is often treated with extracorporeal ultrafiltration. Peritoneal ultrafiltration (PUF) has been proposed for the long-term management of severe HF after resolution of the acute episode. The aim of the present study was to evaluate the use of PUF in the treatment of chronic refractory HF in patients without end-stage renal disease