Design and methodology of the impact of HemoDiaFIlTration on physical activity and self-reported outcomes: a randomized controlled trial (HDFIT trial) in Brazil.

BACKGROUND: End stage renal disease (ESRD) patients require a renal replacement therapy (RRT) to filter accumulated toxins and remove excess water, which are associated with impaired physical function. Hemodialysis (HD) removes middle-molecular weight (MMW) toxins less efficiently compared to hemodiafiltration (HDF); we hypothesized HDF may improve physical function. We detailed the design and methodology of the HDFIT protocol that is testing whether changing from HD to HDF effects physical activity levels and various outcomes. METHODS: HDFIT is a prospective, multi-center, unblinded, randomized control trial (RCT) investigating the impact of dialysis modality (HDF verses HD) on objectively measured physical activity levels, self-reported quality of life, and clinical/non-clinical outcomes. Clinically stable patients with HD vintage of 3 to 24 months without any severe limitation ambulation were recruited from sites throughout southern Brazil. Eligible patients were randomized in a 1:1 ratio to either: 1) be treated with high volume online HDF for 6 months, or 2) continue being treated with high-flux HD. This study includes run-in and randomization visits (baseline), 3- and 6-month study visits during the interventional period, and a 12-month observational follow up. The primary outcome is the difference in the change in steps per 24 h on dialysis days from baseline to the 6-month follow up in patients treated with HDF versus HD. Physical activity is being measured over one week at study visits with the ActiGraph ( www.actigraphcorp.com ). For assessment of peridialytic differences during the dialysis recovery period, we will analyze granular physical activity levels based on the initiation time of HD on dialysis days, or concurrent times on non-dialysis days and the long interdialytic day. DISCUSSION: In this manuscript, we provide detailed information about the HDFIT study design and methodology. This trial will provide novel insights into peridialytic profiles of physical activity and various self-reported, clinical and laboratory outcomes in ESRD patients treated by high volume online HDF versus high-flux HD. Ultimately, this investigation will elucidate whether HDF is associated with patients having better vitality and quality of life, and less negative outcomes as compared to HD. TRIAL REGISTRATION: Registered on ClinicalTrials.gov on 20 April 2016 ( NCT02787161 ).

Icodextrin reduces insulin resistance in non-diabetic patients undergoing automated peritoneal dialysis: results of a randomized controlled trial (STARCH).

BACKGROUND: Insulin resistance is a common risk factor in chronic kidney disease patients contributing to the high cardiovascular burden, even in the absence of diabetes. Glucose-based peritoneal dialysis (PD) solutions are thought to intensify insulin resistance due to the continuous glucose absorption from the peritoneal cavity. The aim of our study was to analyse the effect of the substitution of glucose for icodextrin on insulin resistance in non-diabetic PD patients in a multicentric randomized clinical trial. METHODS: This was a multicenter, open-label study with balanced randomization (1:1) and two parallel-groups. Inclusion criteria were non-diabetic adult patients on automated peritoneal dialysis (APD) for at least 3 months on therapy prior to randomization. Patients assigned to the intervention group were treated with 2L of icodextrin 7.5%, and the control group with glucose 2.5% during the long dwell and, at night in the cycler, with a prescription of standard glucose-based PD solution only in both groups. The primary end-point was the change in insulin resistance measured by homeostatic model assessment (HOMA) index at 90 days. RESULTS: Sixty patients were included in the intervention (n = 33) or the control (n = 27) groups. There was no difference between groups at baseline. After adjustment for pre-intervention HOMA index levels, the group treated with icodextrin had the lower post-intervention levels at 90 days in both intention to treat [1.49 (95% CI: 1.23-1.74) versus 1.89 (95% CI: 1.62-2.17)], (F = 4.643, P = 0.03, partial η(2) = 0.078); and the treated analysis [1.47 (95% CI: 1.01-1.84) versus 2.18 (95% CI: 1.81-2.55)], (F = 7.488, P = 0.01, partial η(2) = 0.195). CONCLUSIONS: The substitution of glucose for icodextrin for the long dwell improved insulin resistance measured by HOMA index in non-diabetic APD patients.

Characterization of the BRAZPD II cohort and description of trends in peritoneal dialysis outcome across time periods.

Observational studies from different regions of the world provide valuable information in patient selection, clinical practice, and their relationship to patient and technique outcome. The present study is the first large cohort providing patient characteristics, clinical practice, patterns and their relationship to outcomes in Latin America. The objective of the present study was to characterize the cohort and to describe the main determinants of patient and technique survival, including trends over time of peritoneal dialysis (PD) initiation and treatment. This was a nationwide cohort study in which all incident adult patients on PD from 122 centers were studied. Patient demographics, socioeconomic and laboratory values were followed from December 2004 to January 2011 and, for comparison purposes, divided into 3 groups according to the year of starting PD: 2005/06, 2007/08 and 2009/10. Patient survival and technique failure (TF) were analyzed using the competing risk model of Fine and Gray. All patients active at the end of follow-up were treated as censored. In contrast, all patients who dropped the study for any reason different from the primary event of interest were treated as competing risk. Significance was set to a p level of 0.05. A total of 9,905 patients comprised the adult database, 7,007 were incident and 5,707 remained at least 90 days in PD. The main cause of dropout was death (54%) and of TF was peritonitis (63%). Technique survival at 1, 2, 3, 4, and 5 years was 91%, 84%, 77%, 68%, and 58%, respectively. There was no change in TF during the study period but 3 independent risk factors were identified: lower center experience, lower age, and automated PD (APD) as initial therapy. Cardiovascular disease (36%) was the main cause of death and the overall patient survival was 85%, 74%, 64%, 54%, and 48% at 1, 2, 3, 4, and 5 years, respectively. Patient survival improved along all study periods: compared to 2005/2006, patients starting at 2007/2008 had a relative risk reduction (SHR) of 0.83 (95% confidence interval [CI] 0.72 - 0.95); and starting in 2009/2010 of 0.69 (95% CI 0.57 - 0.83). The independent risk factors for mortality were diabetes, age > 65 years, previous hemodialysis, starting PD modality, white race, low body mass index (BMI), low educational level, center experience, length of pre-dialysis care, and the year of starting PD. We observed an improvement in patient survival along the years. This finding was sustained even after correction for several confounders and using a competing risk approach. On the other hand, no changes in technique survival were found.