End-stage renal disease occurs when the kidneys lose nearly all their ability to function, requiring life-sustaining treatment decisions that can profoundly shape a patient’s remaining years.

Understanding Your Treatment Choices When Kidneys Fail

When the kidneys can no longer filter waste products and maintain the body’s fluid balance well enough to sustain life, patients face critical treatment decisions. This condition, known as end-stage renal disease or ESRD, typically develops after years of progressive kidney damage, most often caused by diabetes, high blood pressure, or other chronic conditions that gradually erode kidney function.^[2] At this stage, kidney function has typically declined to less than 15% of normal capacity, creating a situation where dangerous levels of toxins, fluids, and minerals accumulate in the body.^[1]

The primary goals of treatment focus on replacing lost kidney function to sustain life, managing symptoms that arise from kidney failure, and maintaining the best possible quality of life given individual circumstances and preferences. Treatment approaches vary significantly depending on whether a patient chooses active replacement therapy through dialysis or transplantation, or opts for conservative medical management aimed at comfort and symptom control.^[9] Each path involves careful consideration of the patient’s overall health, other medical conditions, personal values, and life goals.

Medical societies and kidney specialists have developed comprehensive guidelines to help patients and doctors navigate these complex decisions. The Kidney Disease: Improving Global Outcomes (KDIGO) foundation provides frameworks for staging kidney disease and guiding management based on how well the kidneys are filtering blood and whether protein is leaking into the urine.^[2] Despite these guidelines, many patients unfortunately begin dialysis without adequate preparation, prior consultation with kidney specialists, proper access placement for dialysis, or education about their treatment options, leading to poorer outcomes and missed opportunities for better care.^[2]

Importantly, ongoing research continues to explore new therapies and approaches that may improve outcomes for people living with kidney failure. Clinical trials test innovative treatments that could potentially enhance quality of life, reduce complications, or improve the effectiveness of existing therapies, offering hope for better management strategies in the future.

Standard Treatment Approaches for Kidney Failure

Dialysis: Replacing Kidney Function

Dialysis is a medical procedure that artificially performs the work that healthy kidneys normally do—removing waste products, excess fluids, and toxins from the blood while helping maintain proper mineral and chemical balance in the body.^[7] For most patients with ESRD, dialysis becomes necessary when kidney function drops below 15% of normal levels, though the exact timing depends on symptoms and laboratory test results.^[7]

There are two main types of dialysis available. Hemodialysis is the most common form, used by the majority of dialysis patients. During hemodialysis, blood is pumped from the body through a special filter called a dialyzer (often called an artificial kidney) that removes wastes and excess fluid before returning the cleaned blood to the body.^[13] This procedure typically requires three sessions per week, with each session lasting about four hours. For hemodialysis to work effectively, patients need a vascular access point—either an arteriovenous fistula (a surgical connection between an artery and vein), an arteriovenous graft (using synthetic tubing), or a central venous catheter.^[9]

The second type, peritoneal dialysis, uses the lining of the abdomen (the peritoneum) as a natural filter. A cleansing fluid called dialysate is introduced into the abdominal cavity through a permanently placed catheter, where it absorbs wastes and excess fluid from blood vessels in the peritoneal lining. After several hours, the fluid is drained and replaced with fresh solution.^[13] This can be done manually several times throughout the day or automatically overnight using a machine while the patient sleeps. Peritoneal dialysis offers more flexibility and can often be performed at home, allowing patients greater independence in their daily activities.

Medicare coverage for dialysis typically begins on the first day of the fourth month after dialysis treatments start, though coverage can begin as early as the first month if patients participate in a home dialysis training program and complete the training successfully.^[3] Patients need to work closely with a dialysis care team that typically includes nephrologists (kidney doctors), dialysis nurses, dietitians, and social workers who coordinate to provide comprehensive care.^[13]

Kidney Transplantation

Kidney transplantation involves surgically placing a healthy kidney from a donor into a person whose kidneys no longer work adequately. This single healthy kidney can perform the work of two failed kidneys. Transplantation typically offers the best patient outcomes compared to long-term dialysis, often providing better quality of life, fewer dietary restrictions, and improved survival rates.^[9]

Kidneys for transplantation come from two sources. Living donor transplants involve receiving a kidney from a living person, often a family member, friend, or even an altruistic stranger willing to donate. Living donation allows for scheduled surgery and often results in better kidney function because the organ experiences less time outside the body.^[13] Deceased donor transplants use kidneys from people who have died and chosen to be organ donors. Patients waiting for deceased donor kidneys are placed on a transplant waiting list, and the wait can vary considerably depending on blood type, tissue matching, and geographic location.^[13]

Medicare coverage for kidney transplant can begin the month a patient is admitted to a Medicare-certified hospital for transplant surgery (or for healthcare services needed before the transplant) if the transplant occurs within the same month or the following two months.^[3] After a successful transplant, patients must take immunosuppressant medications for the rest of their lives to prevent the body’s immune system from rejecting the new kidney.^[13] These anti-rejection medicines help the body accept the foreign organ but can increase susceptibility to infections and have other side effects that require careful monitoring.

Medications to Manage Kidney Disease Progression and Complications

Even when kidney function is severely reduced, certain medications play important roles in managing complications and potentially slowing further decline. Angiotensin-converting enzyme inhibitors (ACE inhibitors) and angiotensin receptor blockers (ARBs) are medications originally developed to treat high blood pressure, but they also help protect the kidneys by reducing protein leakage into the urine and slowing the progression of kidney disease.^[2] These medications work by relaxing blood vessels and reducing pressure within the kidney’s filtering units. Clinical guidelines strongly recommend their use in patients with chronic kidney disease who have protein in their urine, as they can delay progression to end-stage disease.^[8]

Blood pressure control is critically important in ESRD management. Guidelines generally recommend keeping blood pressure below 140/90 mm Hg, though targets may be individualized based on specific patient circumstances.^[9] For patients already receiving dialysis, controlling blood pressure helps reduce mortality risk. Volume control through adequate dialysis and restricting salt intake can help optimize blood pressure management in these patients.^[9]

For patients with both kidney failure and diabetes, insulin is the preferred treatment when medication becomes necessary to control blood sugar levels.^[9] Many oral diabetes medications need dose adjustments or should be avoided entirely when kidney function is severely reduced because they can accumulate to dangerous levels or cause other complications. Maintaining blood sugar within target ranges remains important even with kidney failure, as good control can help prevent additional complications affecting the eyes, nerves, and cardiovascular system.

Other common medications address specific complications of kidney failure. Patients often need medications to correct anemia (low red blood cell counts) that develops when failing kidneys cannot produce enough erythropoietin, a hormone that stimulates red blood cell production. Medications called phosphate binders help control high phosphorus levels that occur because diseased kidneys cannot adequately remove this mineral, which can lead to bone disease and vascular calcification if left untreated.^[2] Vitamin D supplements may be prescribed because the kidneys normally activate this vitamin, and deficiency contributes to bone and mineral disorders common in kidney failure.

Conservative Medical Management and Palliative Care

Not all patients choose to pursue dialysis or transplantation. A palliative or conservative approach to ESRD management is a reasonable alternative, particularly for individuals with limited life expectancy, severe coexisting medical conditions, or those who prefer to avoid intensive medical interventions.^[9] This approach focuses on maximizing quality of life, managing symptoms, and providing comfort rather than replacing kidney function.

Conservative management involves close symptom monitoring and treatment, careful medication management to avoid kidney-toxic drugs, dietary adjustments to reduce uremic symptoms, and psychosocial support for patients and families. The goal is to help patients live as comfortably as possible for their remaining time while honoring their values and treatment preferences. Hospice care may be integrated when appropriate to provide additional support. This is an important option that deserves full discussion between patients, families, and healthcare providers as part of shared decision-making about ESRD treatment.^[9]

Duration and Monitoring of Treatment

Treatment for end-stage renal disease is almost always lifelong unless a successful kidney transplant restores adequate kidney function. Even with a successful transplant, patients must continue taking immunosuppressant medications indefinitely to prevent organ rejection.^[18] Patients on dialysis require treatment multiple times per week for the rest of their lives or until they receive a transplant.

Regular monitoring is essential regardless of treatment approach. Patients need frequent blood tests to check waste product levels, mineral balance, anemia status, and medication levels. Dialysis patients require ongoing assessment of dialysis adequacy to ensure treatments are effectively removing toxins. Transplant recipients need regular kidney function monitoring and immunosuppressant drug level checks.^[19] Healthcare teams typically schedule appointments monthly or more frequently as needed to track disease progression, adjust treatments, and address emerging complications.

Common Side Effects and Complications

Dialysis and medications used in ESRD management can cause various side effects. During or after hemodialysis sessions, patients may experience muscle cramps, itching, low blood pressure causing dizziness, nausea, fatigue, and headaches. There is also infection risk at the access site and potential for blood clots in the access.^[7] Peritoneal dialysis can lead to peritonitis (infection of the abdominal lining), hernias from the pressure of fluid in the abdomen, weight gain from the sugar in dialysate fluid, and catheter site infections.

The disease itself causes numerous complications that persist despite treatment. These include anemia leading to fatigue and weakness, bone disease from mineral imbalances, high potassium levels that can cause dangerous heart rhythm abnormalities, fluid accumulation causing swelling and shortness of breath, and metabolic acidosis (excessive acid in the blood).^[2] Patients often experience decreased appetite, nausea, vomiting, changes in taste, and sleep disturbances. Cardiovascular complications are common, as ESRD significantly increases risk for heart disease, stroke, and sudden cardiac death. Many patients also struggle with depression, anxiety, and reduced quality of life from the burden of chronic illness and demanding treatment schedules.

Promising Treatments Being Studied in Clinical Trials

Research into new treatments for end-stage renal disease continues actively, with clinical trials testing various innovative approaches aimed at improving outcomes, reducing complications, and enhancing quality of life for patients living with kidney failure. While standard treatments like dialysis and transplantation remain the mainstays of ESRD management, ongoing research explores modifications and enhancements that could make these treatments more effective or better tolerated.

Understanding Clinical Trial Phases

Clinical trials for kidney disease treatments progress through distinct phases, each designed to answer specific questions about safety and effectiveness. Phase I trials represent the earliest stage of testing in humans, focusing primarily on determining whether a new intervention is safe and identifying appropriate dosing ranges. These studies typically involve small numbers of participants and carefully monitor for side effects and how the body processes the treatment. Phase I trials for kidney disease might test whether a new medication accumulates to dangerous levels in people with reduced kidney function or whether a modified dialysis technique causes unexpected complications.

Phase II trials expand testing to larger groups of patients who actually have the disease being studied. These trials primarily assess whether the treatment shows signs of working—does it improve laboratory markers of kidney function, reduce symptoms, or demonstrate beneficial effects through other measurable outcomes? Phase II studies also continue gathering safety information and refining appropriate doses. For example, a Phase II trial might test whether a new medication reduces protein loss in the urine or whether a different dialysis schedule improves patient-reported energy levels and quality of life.

Phase III trials represent the most rigorous testing phase, typically comparing the new treatment directly against current standard treatments in large numbers of patients. These studies determine whether the new approach is as good as, or better than, existing therapies and provide definitive evidence about benefits and risks. A Phase III trial might randomly assign hundreds of patients to receive either conventional hemodialysis or a new dialysis technology, then follow them for months or years to compare survival, hospitalization rates, and quality of life.

Phase IV trials occur after a treatment has been approved and is in widespread use. These studies continue monitoring long-term effects, identify rare side effects that might not have appeared in earlier trials, and explore whether the treatment works in populations not included in initial studies, such as older adults or people with multiple medical conditions.

Innovations in Dialysis Technology

Researchers are actively investigating ways to make dialysis more effective, convenient, and less burdensome for patients. Some clinical trials explore more frequent or longer dialysis sessions—for example, short daily hemodialysis treatments or nocturnal dialysis performed overnight while patients sleep. Early research suggests these modified schedules might better control fluid accumulation, improve blood pressure management, and enhance quality of life, though they require significant commitment and lifestyle adjustment.

Other trials test technological improvements to dialysis equipment. Wearable artificial kidney devices are being developed that could potentially allow continuous dialysis while patients remain mobile, eliminating the need to be connected to large stationary machines several times weekly. While still in early development phases, these devices represent a potentially transformative approach that could dramatically improve patient freedom and quality of life if proven safe and effective.

Studies also examine whether modifying the composition of dialysate (the cleansing fluid used in dialysis) might reduce complications or improve outcomes. For instance, some trials test whether adjusting bicarbonate concentrations affects acid-base balance, or whether modifying potassium levels in the dialysate better prevents dangerous heart rhythm disturbances.

Advances in Transplantation

Clinical research in kidney transplantation explores multiple fronts. One exciting area involves xenotransplantation—using organs from animals, particularly genetically modified pigs, for transplantation into humans. Recent clinical trials have begun testing pig kidney transplants in human recipients, representing a potentially revolutionary approach to addressing the critical shortage of human donor organs.^[10] These early trials focus intensively on safety, immune response, and whether pig kidneys can function adequately in human recipients. While extremely preliminary, this research could eventually provide an unlimited supply of organs for patients waiting for transplants.

Other transplant research examines new immunosuppressant medications or treatment regimens that might prevent rejection more effectively while causing fewer side effects like increased infection risk or cancer development. Some trials test whether specific combinations of anti-rejection drugs work better than current standard regimens, or whether lower doses might adequately prevent rejection while reducing medication-related complications.

Researchers are also investigating ways to improve tolerance of transplanted organs. Some studies explore whether specific preparatory treatments before transplant might “teach” the recipient’s immune system to better accept the foreign kidney, potentially reducing the need for lifelong high-dose immunosuppression.

Medications Targeting Kidney Disease Progression and Complications

Although prevention of progression to ESRD is most effective in earlier kidney disease stages, research continues exploring whether specific medications might preserve remaining kidney function or reduce complications even in advanced disease. New classes of diabetes medications called SGLT2 inhibitors and GLP-1 receptor agonists have shown promise in slowing kidney disease progression in people with diabetes in earlier disease stages, and trials are examining whether these benefits extend to patients with more advanced kidney failure.^[13]

A medication called finerenone, which blocks certain hormone receptors involved in inflammation and scarring, has demonstrated benefits in slowing kidney disease progression in some patient populations, and ongoing trials continue evaluating its role in kidney disease management.^[13] These studies examine not only kidney-related outcomes but also cardiovascular effects, since heart disease represents a major cause of death in people with kidney failure.

Other research focuses on better treatments for specific complications of ESRD. For example, clinical trials test new medications for treating anemia that work differently than current standard drugs, potentially offering alternatives for patients who don’t respond well to existing treatments. Studies examine novel phosphate binders that might more effectively control mineral imbalances while causing fewer gastrointestinal side effects. Research also explores treatments for the severe itching (pruritus) that plagues many dialysis patients and significantly impairs quality of life.

Eligibility and Locations for Clinical Trials

Clinical trials for kidney disease treatments are conducted at major medical centers and research institutions worldwide, including locations in the United States, Europe, and other regions. The National Kidney Foundation and other organizations maintain directories of ongoing kidney disease clinical trials that patients can search by location and specific condition.^[10]

Eligibility to participate in a clinical trial depends on the specific study requirements. Trials typically have detailed inclusion and exclusion criteria based on factors such as kidney function level, whether the patient is on dialysis, presence of other medical conditions, age, and current medications. Some trials specifically seek participants who have not yet started dialysis, while others focus on patients already receiving specific treatments. Importantly, participation is always voluntary, and patients can withdraw at any time without affecting their regular medical care.

Potential participants should thoroughly discuss clinical trial options with their kidney doctors. Healthcare providers can help determine whether specific trials might be appropriate and explain potential benefits and risks. Many trials provide the investigational treatment at no cost and may cover some trial-related expenses, though this varies by study.^[13]

Most common treatment methods

• Dialysis
  • Hemodialysis: Blood is filtered through an external machine several times weekly to remove waste products and excess fluid, typically requiring three four-hour sessions per week at a dialysis center or potentially at home with appropriate training.
  • Peritoneal dialysis: Uses the lining of the abdomen as a natural filter, with cleansing fluid introduced and drained through a permanently placed catheter, can be performed manually throughout the day or automatically overnight at home.
  • Home dialysis training programs: Medicare-certified training allows patients to learn to perform their own dialysis treatments at home, enabling earlier Medicare coverage starting the first month of regular dialysis for those who complete training.
• Kidney Transplantation
  • Living donor transplant: Surgical placement of a healthy kidney from a living donor (family member, friend, or altruistic stranger), typically offers best outcomes with better kidney function and can be scheduled in advance.
  • Deceased donor transplant: Transplantation of a kidney from a person who has died and chosen to be an organ donor, requires placement on a waiting list with wait times varying by blood type and location.
  • Immunosuppressant therapy: Lifelong medications required after transplant to prevent the body’s immune system from rejecting the donated kidney, includes various drug combinations that must be carefully monitored.
• Medications for Disease Management
  • ACE inhibitors and ARBs: Blood pressure medications that also help protect kidneys by reducing protein leakage and slowing disease progression, recommended in patients with proteinuria.
  • Insulin: Preferred medication for controlling blood sugar in patients with both ESRD and diabetes, as many oral diabetes drugs must be avoided or adjusted with kidney failure.
  • Anemia treatments: Medications to stimulate red blood cell production when failing kidneys cannot produce adequate erythropoietin hormone.
  • Phosphate binders: Medications that help control high phosphorus levels by preventing its absorption from food, necessary because diseased kidneys cannot adequately remove this mineral.
  • SGLT2 inhibitors and GLP-1 receptor agonists: Newer diabetes medication classes showing promise for slowing kidney disease progression, currently being studied in clinical trials for various stages of kidney disease.
  • Finerenone: A medication that blocks hormone receptors involved in inflammation and scarring, being investigated for its role in slowing kidney disease progression and reducing cardiovascular complications.
• Conservative Medical Management and Palliative Care
  • Symptom-focused treatment: An approach that manages symptoms and maximizes quality of life without pursuing dialysis or transplantation, appropriate for patients with limited life expectancy, severe coexisting conditions, or those preferring to avoid intensive interventions.
  • Careful medication management: Avoiding kidney-toxic drugs and adjusting medication doses appropriately for reduced kidney function.
  • Dietary modifications: Adjustments to reduce uremic symptoms while maintaining adequate nutrition.
  • Hospice care integration: Additional support services for comfort-focused care in patients choosing conservative management.