Criteria for progression
The number of weekly sessions of the patients in the experimental group will be increased from one to two sessions in case they meet any of the following criteria:
KrU [
21] level decline (below 4 ml and above 2.5 ml/min/1.73 m2). This decrease must be confirmed in a subsequent sample obtained in the next month.
Intersessional weekly weight gain which influences an ultrafiltration (UF) rate higher than 13 ml/kg/hour for a minimum of 3 weeks.
Clinical event that requires non programmed HD sessions (more than one) for its resolution.
Patients with two sessions per week will be changed to the conventional HD method if:
The KrU [
21] level is lower than 2.5 ml/min/1.73m
2. This decrease must be confirmed in a subsequent sample obtained in the next month.
Standard Kt/V is below 2.1 (weekly). This decrease in std. Kt/V must be confirmed in a subsequent sample obtained in the next month.
Intersessional weight gain which influences an ultrafiltration (UF) rate higher 13 ml/kg/hour for a minimum of 3 sessions.
Clinical event that requires non programmed HD sessions for its resolution.
Outcomes
Primary outcome Survival. Duration of trial: 2 years.
Secondary outcomes Hospital admissions for any reason. Duration of trial: 2 years.
RRF maintenance. Duration of trial: 2 years.
Reduction of glomerular filtration rate (GFR) and tubular function.
Average urine volume and percentage of patients with anuria (≤200 ml/day in two consecutive measurements).
Adequacy parameters. Duration of trial: 3, 6, 12, 18 months and 2 years.
Anemia control. Patients whose hemoglobin levels are within the therapeutic range (in %) and the average levels of erythropoietin resistance index (ERI in UI/Kg/week).
Mineral bone disorder control. Calcium, phosphorus and Parathyroid hormone (PTHi) average levels. Percentage of patients with levels within therapeutic range.
Specific cardiomyopathy control. Duration of trial: 12 and 24 months. Left ventricular ejection fraction (LVEF). Percentage of patients with a left ventricular mass index (LVMI) adjusted to the body surface area ≥ 125 g/m2, or with pericardial effusion.
Quality of life control. Assessed through the Kidney Disease and Quality of Life Kidney Disease and Quality of Life (KDQOL´36 SF) survey.
Intervention’s cost-efficiency ratio: expressed as increased cost per additional quality adjusted life year (QALY) see Additional file
2.
Sample size It was calculated based in the contrast of a null hypothesis H0: The rate between the median survival time is not under the limit of no inferiority, through a Log-Rank test for two independent samples (no-inferiority in a function of exponential survival).
Assuming the following parameters: Inclusion period of 18 month, maximum duration of the follow-up period: 24 months, survival median in the conventional HD group: 74 months, time median until censure: 12 months, non-inferiority limit: 4 months, type I error 5% (significance), and type II error 20% (capability). We must include 76 patients for the conventional HD group and 76 in incremental HD group, totaling 152 patients in the trial.
Randomization One centralized list has been designed. It includes 152 randomization codes (sample size), and 24 additional ones in case more patients were added. It has two strata: for age (≥or < 75 years old) and for KrU [
21] (≥or < 5,5 ml/min/1.73m
2). The main researcher of each center will formally request the randomization to the Clinical Research Office.
Centralized prescription of the dialysis dose The patient will receive a “centralized prescription” of the dialysis dose, which will be computed quantitatively for each patient. It will be based on the eKt / V necessary according to the KrU of each patient, to obtain an EKRU of 12-KrU ml/min/1.73 m2 on a once-weekly HD and a stdKt/V of 2.3 weekly volumes for twice -and thrice- weekly HD schedules, as published by Casino and Basile [
22]. All calculations involving the urea kinetic model (UKM) are based on of the prescription tool [
23] and the ‘Solute-Solver’ software [
24] (see Additional file
3). The control group will receive a dose of spkt/V of 1.4 per session, neglecting the residual renal function, as collected by the KDOQI [
1].
Note: The KDOQI [
1] suggested aiming at stdKt/V = 2.3
v/
wk. for HD schedules other than thrice weekly HD. But they didn’t mention the once-weekly schedule. So, we adopted the recently suggested variable target for EKRU as a guide for once weekly schedule, that seems quite in agreement with our empirical experience.
Variables Data will be obtained from the patient’s clinical history. The researchers will fulfill an electronic case report form (eCRF) within the proper periods of time.
Demographic data, clinical data and tests run: Biochemical determinations, diagnostic tests and their frequency are registered in Table
1. They are the ones that are usually recommended in the guidelines for these patients.
Survival: The follow-up time will be determined in days. It will be defined as the difference in days from the date of the end of the follow-up minus the date of the baseline visit. Events will be counted either as deaths (follow-up of less than 24 months) or as end of the follow-up (24 months).
Hospital admissions: The number of admissions and the admission days will be registered. The following list will be considered as reasons for direct admissions: infections, vascular access, heart failure or ischemic cardiopathology, gastrointestinal bleeding, or other reasons.
RRF maintenance rate: The GFR (in ml/min) will be calculated with the average residual urea and creatinine clearance. The tubular function will be calculated through fractional excretion of phosphorus and uric acid.
Anemia control: The hemoglobin (in g/dl) and the erythropoiesis-stimulating agents (ESA) dose will be measured (in UI).
Mineral bone disorder control: serum phosphorus and calcium levels (in mg/dl), and intact PTH (in pg/dl) will be measured.
Specific cardiomiopathy control: The LVEF (in %), the LVMI (in g/m2) will be measured, and the presence of pericardial effusion will be assessed.
Quality of life: The items from KDQOL’36 SF survey will be measured.
Intervention’s cost-efficiency ratio: During the follow-up, the costs of each patient will be calculated [
25]. (see Additional file
2).