Most patients who receive hemodialysis treatments have excess fluid in their body that has slowly built up over the course of kidney disease. This extra fluid is the main cause of high blood pressure in dialysis and leads to stress on the heart and lungs.that causes debilitating symptoms and frequent hospitalizations.

This trial will test whether a focused program of 4 or 8 weeks of extra ultrafiltration treatments can remove most of this extra fluid. We believe that getting rid of large amounts of extra fluid will result in sustained improvements in blood pressure and symptoms. Ultrafiltration is a gentler type of dialysis that removes fluid but does not clean the blood.

This is a randomized trial of patients who are receiving in-center hemodialysis treatments for end stage kidney disease and have clinical suspicion of fluid overload. Enrolled participants will be randomly assigned in 1:1:1 fashion to either a four-week ultrafiltration strategy, an eight-week ultrafiltration strategy, or continuation of their regular thrice weekly hemodialysis treatments. Each ultrafiltration strategy will add two extra four-hour ultrafiltration treatments per week plus pharmacist-guided tapering of blood pressure medications. We will test the impact of these strategies on primary outcomes of

1. Change in 24-hour continuous ambulatory blood pressure from baseline to 24-weeks
2. Change in symptoms of congestion from baseline to 24-weeks We will also test the impact of the treatment strategies on related symptoms, physical activity levels, hemodynamics. and measures of safety.

Inclusion Criteria:

• Receiving thrice weekly in-center hemodialysis treatments for end stage kidney disease for at least four weeks and clinical suspicion of volume excess based on either:

  1. Persistent hypertension defined by three consecutive pre-dialysis systolic blood pressures ≥140 mmHg or three consecutive pre-dialysis systolic blood pressures 130-140 mmHg plus use of at least two anti-hypertensive medications that can be tapered.

     OR

  2. Symptoms of congestion defined by a 12-item Kidney Modified Kansas City Cardiomyopathy Questionnaire (KM-KCCQ) score <75.

     Exclusion Criteria:

• Age <18 years

• Receiving hemodialysis treatments for acute kidney injury

• Receiving hemodialysis treatments for less than four weeks

• Planned switch to peritoneal or home dialysis within next three months

• Current or planned incremental hemodialysis (less than 3 treatments per week)

• Current or planned intensive hemodialysis (four or more treatments per week)

• Scheduled kidney transplantation

• Major cardiovascular or bleeding event within previous 90 days

• Receiving chemotherapy or radiation treatment for cancer

• History of cirrhosis with ascites

• Inability to complete 24-hour ambulatory blood pressure measurement

• Wheelchair dependance or other inability to complete six-minute walk test

• Pre-dialysis systolic blood pressure <100 mmHg

• Scheduled use of midodrine with hemodialysis treatments

• History of non-adherence with dialysis treatments

• Pregnancy

• Institutionalized

• Current or pending enrollment in hospice care

• Inappropriate for enrollment based on investigator or nephrologist discretion

All data and samples will be stored indefinitely for possible future uses. There will be no direct or indirect identifiers stored with the resources after this study is finished.

Resources will be coded with study codes. We plan post de-identified data in public databases such as Dryad at study conclusion.

NIH data sharing policies typically require us to post coded, deidentified individual-level data on one of the preferred platforms. We will work with our NIH project officer to post data after the study is finished to an appropriate platform.

We may collaborate with colleagues and other researchers who demonstrate a legitimate research need for which data and samples from this study would be valuable.

Future uses do not have any restrictions.

We will share the study protocol, informed consent form, and statistical analysis plan at the beginning of the study and indefinitely. We will share the analytic code when it becomes available.