How Does Personalized Hemodialysis Compare to Traditional Hemodialysis?
VIDEO: An Overview of the TwoPlus Study
VIDEO: How to Perform Timed Urine Collection to Monitor Residual Kidney Function
What is this research about?
This study is the TwoPlus Clinical Trial. It examines an alternative approach to chronic hemodialysis. The study is for patients who need renal replacement therapy (dialysis). This condition is called end-stage kidney disease. Many people with end stage kidney disease benefit from three hemodialysis sessions per week. Some individuals who start dialysis with reasonable residual kidney function can start treatments with less frequent hemodialysis. Two hemodialysis sessions per week, may be sufficient until residual kidney function decreases. Dialysis treatments that start with two hemodialysis sessions per week and then increase to three hemodialysis sessions per week is called incremental hemodialysis. This is a form of personalized hemodialysis. This study compares personalized hemodialysis (incremental) with traditional dialysis of three hemodialysis sessions per week.
Where does this research take place?
The TwoPlus Clinical Trial is funded by Patient-Centered Outcomes Research Institute (PCORI). The study takes place at ten healthcare systems and more than fifty outpatient dialysis units in the United States. The study is conducted in collaboration with patient-led organizations like the American Association of Kidney Patients and Home Dialyzors United.
Who can join the study?
Patients who are starting hemodialysis and have residual kidney function will be evaluated for eligibility to take part in this study. The patient’s kidney doctor and the site investigators will decide if the patient can join the study. Patients who do not have enough residual kidney function will not be eligible for this study. A full list of eligibility criteria is listed below.
Eligible patients have all the conditions below around the time hemodialysis is started:
- Age ≥ 18 years
- New-onset kidney dysfunction requiring dialysis (also known as end-stage kidney disease [ESKD] or end-stage renal disease [ESRD] or chronic kidney disease stage 5 on dialysis [CKD5D]) starting in-center, chronic hemodialysis, or anticipated to be started on in-center, chronic hemodialysis within the next 12 weeks
- Has received ≤36 sessions of hemodialysis (i.e., on hemodialysis for ≤12 weeks) when approached for potential study participation
- Kidney urea clearance ≥2.0 mL/min
- Urine volume of ≥500 mL/24 h
Eligible patients have none of the conditions below around the time hemodialysis is started:
- Serum potassium level that is persistently ≥5.8 mEq/L
- Serum sodium level that is persistently ≤125 mEq/L
- Serum bicarbonate level that is persistently ≤17 mEq/L
- Requirement or anticipated requirement of high-volume fluid removal
- History of medical non-adherence that, in the opinion of the site investigators and/or treating providers, precludes safe study participation
- A medical condition that, in the opinion of the site investigators and/or treating providers, would jeopardize the safety of the patient
- Expected dialysis modality change (e.g., home hemodialysis, peritoneal dialysis) or kidney transplantation within the next 6 months
- Estimated survival of <6 months, in the opinion of the site investigators and/or treating providers
- Estimated transfer to a dialysis facility outside the care of the participating study team within the next 6 months
- Known pregnancy or planning to attempt to become pregnant or lactating women
- Unable or unwilling to follow the study protocol for any reason
What is the research team doing?
During the study, investigators, treating providers, and dialysis providers monitor all hemodialysis treatments. Residual kidney function is monitored.
This is done by collecting a timed urine specimen by patients who are enrolled in the study. Patients’ clinical condition and blood tests are routinely monitored. Medications and hemodialysis treatments will change throughout the study as clinical conditions require. The safety of patients enrolled in the study is maintained at all times. When residual kidney function decreases, individualized hemodialysis will advance from two hemodialysis sessions per week to three sessions per week. A decrease in residual function is when clinical conditions report a urea clearance <2.5 mL/min/1.73 m2 and/or Urine volume of <500 mL/24 h. When that happens, more frequent hemodialysis sessions may be required each week, depending on what the individual needs to achieve the best clinical outcome.
The study team will compare safety and health outcomes between individualized (incremental) and traditional hemodialysis. Emergency department visits, hospital admissions, patient and care partner quality of life, and other measures will be compared.
What does this research entail for the patients enrolled in the study?
Patients enrolled in the study will collect their urine every three months, or more often when clinically indicated.
Activities that involve patient participants:
- Patients will receive guidance as to how and when to perform the urine collection during a 24 hour +/- of time.
- Patients will be asked to tell the study team how they feel and answer questionnaires.
- Patients will have blood tests and medications assessed and relayed to on a regular basis.
- Patients will be asked if willing to participate in brief interviews to provide feedback about the study and their hemodialysis.
- Patients assigned to two hemodialysis sessions per week will switch to three hemodialysis sessions per week when their residual kidney function worsens, or their medical conditions would benefit from additional hemodialysis treatments.
- Patients will be followed in the study for up to five years.
What are the risks of being in this study?
People in the Personalized Hemodialysis Treatment Group:
No one knows whether people in the Personalized Hemodialysis Treatment Group (two-times per week hemodialysis followed by three-times per week hemodialysis) have fewer or greater risks overall than the Traditional Hemodialysis Treatment Group (three-times per week hemodialysis).
Possible risks of being in the Personalized Hemodialysis Treatment Group are:
More fluid and salt built up in the body (lungs, heart, legs, brain). This can happen if:
- Fluid pills (diuretics) are not taken on the days without dialysis, and/or
- Hemodialysis does not progress from two-times per week to three-times per week when the residual kidney function decreases
More acid and potassium built up in the body (lungs, heart, legs, brain). This can happen if:
- Bicarbonate pills are not taken on the days without dialysis, and/or
- Potassium-binder is not taken when advised, and/or
- Hemodialysis is not switched to three-times per week when the kidney function decreases
More toxins built up in the body (lungs, heart, legs, brain). This can happen if:
- Hemodialysis is not switched to three-times per week when the kidney function decreases
People in the Traditional Hemodialysis Treatment Group:
No one knows whether people in the Traditional Hemodialysis Treatment Group (three-times per week hemodialysis) have fewer or greater risks overall than the Personalized Hemodialysis Treatment Group two-times per week hemodialysis followed by three-times per week hemodialysis).
Possible risks of being in the Traditional Hemodialysis Treatment Group are:
More fluid and salt built up in the body (lungs, heart, legs, brain). This can happen if:
- Hemodialysis treatments are missed
More acid and potassium built up in the body (lungs, heart, legs, brain). This can happen if:
- Hemodialysis treatments are missed
More toxins built up in the body (lungs, heart, legs, brain). This can happen if:
- Hemodialysis treatments are missed
Procedures to follow during the study to avoid risks:
Several procedures ought to be followed in order to avoid the risks described above and to maintain the validity of the study. Overall, the most important rules to follow are to:
- Collect and bring the urine in the months you are advised
- Take medications as recommended; and
- Do not miss hemodialysis treatments.
We divided below the instruction based on schedules of two-times per week or three-times per week hemodialysis.
Procedures to follow to avoid risks while on two-times per week hemodialysis:
- Take fluid pills (diuretics) and bicarbonate pills on non-dialysis days
- Do not miss dialysis treatments
- Bring urine collection in the months you are advised
- Take potassium-binder if you are advised
- Switch to three-times per week hemodialysis when recommended by your kidney doctor
Procedures to follow to avoid risks while on three-times per week hemodialysis:
- Do not miss dialysis treatments
- Bring urine collection in the months you are advised
- Take medications as recommended by your doctors
What does this research entail for the care partners enrolled in the study?
Care partners will be asked to tell the study team how they feel and answer questionnaires. Care partners may also participate in interviews and provide feedback about the study and hemodialysis.
How do patients and stakeholders make this project successful?
The study team collaborates with clinical physicians, dialysis nurses, dialysis dietitians, and dialysis social workers to seamlessly incorporate the study into the daily workflows of hemodialysis care. Our team will get feedback from advisory panels of patients, care partners, and healthcare providers from all participating centers. The study team will also work with patient advocacy organizations to share information about this study and the results of the study with the public.
Who can this research help?
This research will help patients, care partners, providers and society in general. The study hopes to find a treatment that is safe and that will improve the quality of life for people treated with hemodialysis and for their care partners.
Why is this study important to patients?
- Kidney disease is one of the fastest-growing medical conditions, the 10th leading cause of death worldwide.
- Traditional hemodialysis was based on research in patients with no residual kidney function, even though almost 1 in 4 patients still have residual kidney function when they start hemodialysis treatments.
- Studies have found that an incremental treatment plan for hemodialysis (two hemodialysis sessions per week and then three hemodialysis sessions per week) is both safe and effective for patients who have residual kidney function—but not for those who do not have appreciable residual kidney function. This study takes an unbiased approach to rigorously compare the effectiveness of personalized, incremental hemodialysis and traditional hemodialysis. This study will help patients, care partners and providers make better decisions about what treatment plan is best for each individual.