Continuing Education Activity

Dialysis is a form of renal replacement therapy. The kidney’s role of filtration of the blood is supplemented by artificial equipment to remove excess water, solutes, and toxins. Dialysis ensures maintenance of homeostasis (a stable internal environment) in people experiencing a rapid loss of kidney function, known as acute kidney injury (AKI), or a prolonged, gradual loss in renal function, called chronic kidney disease (CKD, previously end-stage renal disease, ESRD). It may serve to tide over an acute decline in renal function, buy time until a kidney transplant is performed, or be lifelong for those who are not candidates for transplant. Approximately 2.5 million people worldwide received chronic renal replacement therapy (RRT) in 2010. It is the mainstay in end-stage renal disease management, a renal condition with a rising global burden attributed mainly to diabetes mellitus (45%) and hypertension (30%). There are three primary types of dialysis: hemodialysis, peritoneal dialysis, and hemofiltration. This activity reviews the multiple aspects of the conduction and indications of hemodialysis and highlights the role of the interprofessional team in ensuring adequate physical, psychological, social, and emotional preparedness of patients on long-term hemodialysis and their caregivers.

Objectives:

• Review the history and present status of hemodialysis as a form of renal replacement therapy worldwide.
• Describe the process, equipment, and trained staff, as well as other specifics of the hemodialysis process.
• Summarize the associated complications arising out of hemodialysis and their management.
• Explain the need to ensure teamwork and improved care coordination among the interprofessional team members involved in designing a care plan for renal replacement therapy, creating vascular access, and maintaining it, along with catering to the psychosocial needs of the patients and their families.

Introduction

The term dialysis is derived from the Greek words dia, meaning "through," and lysis, meaning "loosening or splitting." It is a form of renal replacement therapy, where the kidney's role of filtration of the blood is supplemented by artificial equipment, which removes excess water, solutes, and toxins. Dialysis ensures the maintenance of homeostasis (a stable internal environment) in people experiencing a rapid loss of kidney function, i.e., acute kidney injury (AKI) or a prolonged, gradual loss that is chronic kidney disease (CKD). It is a measure to tide over acute kidney injury, buy time until a kidney transplant can be carried out, or sustain those ineligible for it.

The incidence of renal replacement therapy (RRT) depends on the incidence and prevalence of conditions causing end-stage renal disease (ESRD), early diagnosis of chronic kidney disease (CKD), and measures to slow the progression to end-stage renal disease (ESRD). Systematic identification of patients with a declining estimated glomerular filtration rate (eGFR), heavy proteinuria, and history of acute kidney injury episodes facilitates planned RRT commencement, thus slowing the rising trend in emergency RRT incidence. All patients likely to end up with ESRD and their caregivers must be adequately prepared physically and psychologically and provided with accessible education about future treatment options. Advanced preparation helps avoid dialysis-associated complications such as a malfunctioning catheter or poorly functioning fistula, causing temporary vascular access insertion culminating in sepsis, thrombosis, bleeding, and accelerated mortality. Patients with educational programs are more likely to choose home-based dialysis therapy with societal benefits, less expenditure, and improved quality of life. These programs should commence no later than stage 4 CKD for the patient to have sufficient time and cognition to make informed choices and implement preparatory measures for RRT.

In 2010, approximately 2.5 million people worldwide received chronic RRT, with high absolute rates in North America and maximum prevalence in Taiwan and Japan. Maintenance of regional and national dialysis registries with details on rates, outcomes, and national dialysis practice patterns helps keep track of the population dependent on RRT. They also include hospital-specific information, safety, and quality reporting and provide resources for clinical research. Opting for dialysis is affected by sociocultural and socioeconomic factors. ESRD is disproportionately higher in African Americans and CKD among the White population. ESRD burden is attributed to diabetes mellitus (45%) and hypertension (30%), besides rarer causes like polycystic kidney disease, obstructive nephropathy, and glomerulonephritis. Women are at higher risk for CKD, while men have a higher risk of ESRD. Race disparities can limit access to health care due to their impact on income or the availability of health insurance. Indigenous people in Australia, New Zealand, the United States, and Canada have high rates of kidney disease, less access to transplantation, and poorer outcomes. There are three broad types of dialysis:

• Hemodialysis (HD)
• Peritoneal dialysis (PD)
• Continuous renal replacement therapy (CRRT)

The dynamics of this particular form of renal replacement therapy vary across countries with longer dialysis sessions and slower blood flow rates in Japan. PD is highly prevalent in Hong Kong and the Jalisco region of Mexico, while Home HD is widely adopted in New Zealand and Australia.

The timing for initiation of dialysis is decided after considering the complications of early initiation (unnecessary exposure to IV lines and invasive procedure with risks of infection) against late initiation, causing avoidable volume, metabolic, and electrolyte complications of AKI. Assigning arbitrary urea nitrogen or creatinine level for dialysis initiation is not advisable due to individual variability in uremia symptom severity and renal function. Despite optimal CKD management, patients progress to needing RRT, especially when their eGFR drops below 20 ml/ min/1.73 m2 or they rapidly deteriorate to ESRD within 12 months. The eGFR at dialysis initiation has steadily increased in recent times. In 1996, in the United States, 13% of incident ESRD patients started RRT at an eGFR of 10 ml/min/1.73 m2 or higher. This increased to 43% in 2010 and dropped to 39% in 2015. Waiting for uremic symptoms to set in before commencing RRT had added risks of the patient being malnourished with increased mortality risk. Asking patients to compare their current eating habits and physical activity levels with those 6 to 12 months back helps avoid the lack of awareness. The concept of a 'healthy start,' with dialysis commencing before the onset of severe uremia symptoms, is associated with prolonged survival. An early start will prepone the need for a change of modality or further procedures without any improvement in the quality of life while adding to healthcare costs. The Renal Physicians Association's (RPA) criteria for identifying dialysis patients with a poor prognosis beyond 75 years of age includes:

1. Provider's estimation of the likelihood of patient mortality in the next six months
2. Greatly impaired functional status
3. High comorbidity score
4. Severe chronic malnutrition (low serum albumin)

Quality of life also strongly predicts mortality. It provides a comprehensive toolkit to encourage shared decision-making.

Mortality rates among dialysis patients are markedly higher among younger age groups, primarily attributed to cardiovascular (40%) and infectious causes (10%). High cardiovascular mortality in dialysis patients could be related to shared risk factors such as chronic inflammation, significant changes in extracellular volume, dystrophic vascular calcification, and altered cardiovascular dynamics during dialysis. The study of heart and renal protection (SHARP) having dialysis and non-dialysis requiring CKD patients showed a 17% reduction in cardiovascular death and major cardiovascular events with simvastatin-ezetimibe treatment. Cardioprotective strategies such as beta-blockers, aspirin, and renin-angiotensin-aldosterone system inhibitors are recommended in dialysis patients based on their cardiovascular risk profile. Hypertension has a graded association with ESRD risk as it is both a cause and a consequence of CKD. The first three months after dialysis initiation, especially among older patients, has the highest mortality rates. This could be due to risks associated with the commencement of dialysis (central venous catheter placement) and more severe comorbidities causing deterioration of renal function. Effective interprofessional collaboration is needed to improve overall outcomes in patients with ESRD requiring dialysis. 

Anatomy and Physiology

Dialysis involves the removal of solutes across a semipermeable membrane down the concentration gradient by two mechanisms:

1. Diffusive clearance due to random molecular motion. Small molecules have a higher rate of diffusive transport through the membrane
2. A convective clearance occurs when the osmotic force of the water pushes solutes along with it through the membrane (solvent drag)

Dialysate consists of highly purified water with sodium, potassium, magnesium, calcium, bicarbonate, chloride, and dextrose. It lacks low-molecular-weight waste products present in uremic blood. When a semipermeable membrane separates uremic blood and dialysate, the flux rate of waste solutes from blood to dialysate exceeds the back-flux from the dialysate to blood. Eventually, the concentrations of permeable waste products in the dialysate and the blood become equal with no further net removal of the waste products.

During dialysis, a concentration equilibrium is prevented from forming, and the gradient is maintained by continuously refilling fresh dialysis solution in the dialyzer and replacing dialyzed with undialyzed blood. “Countercurrent” flow maximizes the concentration difference of waste products between blood and dialysate. The diffusion rate of a solute depends on the magnitude of the concentration gradient, the mass transfer coefficient of the membrane, and the membrane surface area. The transfer coefficient depends on membrane thickness, solute size, and flow conditions on both sides of the membrane.

The Kt/V urea was a parameter introduced by Gotch and Sargent through their National Cooperative Dialysis Study (1985). It was noted that a Kt/V of less than 0.8 was associated with higher morbidity or treatment failure as opposed to a Kt/V of more than 1.0, which produced a good outcome. It is a dimensionless ratio obtained by dividing the amount of plasma cleared of urea (Kt) by the distribution volume of urea (V). The urea-free plasma volume is a product of K, which is blood urea clearance, and t, which is the dialysis session length. A Kt/V of 1.0 implies that the total blood volume cleared during a session equals the urea distribution volume.

Dialysis may be intermittent or continuous. Continuous intravascular procedures are preferable in those who are hemodynamically unstable or have significant volume overload.

Indications

Hemodialysis initiation is needed for acute illness associated with:

• Acute kidney injury
• Uremic encephalopathy
• Pericarditis
• Life-threatening hyperkalemia
• Refractory acidosis
• Hypervolemia causing end-organ complications (e.g., pulmonary edema)
• Failure to thrive and malnutrition
• Peripheral neuropathy
• Intractable gastrointestinal symptoms
• Asymptomatic patients with a GFR of 5 to 9 mL/min/1.73 m²[1]
• Any toxic ingestion

These conditions cause dysregulation and impaired clearance of cytokines (immune response modulators), causing vasodilation, cardiac depression, and immunosuppression leading to end-organ damage, hemodynamic instability, or delaying renal recovery. RRT enhances cytokine removal in high-cytokine states like sepsis. There is potential harm arising from catheter complications, electrolyte disturbances, and intradialytic hypotension.

The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) has provided the guidelines (2015 update) for hemodialysis adequacy.[2]

It recommends that patients who reach CKD stage 4 (GFR, 30 mL/min/1.73 m^2), and those with an imminent need for maintenance dialysis during the initial assessment, should be counseled about renal failure and the treatment options (kidney transplantation, hemodialysis at home or in-center, PD) and conservative treatment. Family members and caregivers should also be educated. The decision to initiate maintenance dialysis should be based on an assessment of signs and symptoms of renal failure (pruritus, acid-base or electrolyte abnormalities, serositis), volume or BP dysregulation, and a progressive deterioration in nutritional status despite dietary intervention or impairment in cognition. The decision to initiate dialysis should not be based on the level of kidney function in an asymptomatic individual.

Cardiac conditions requiring dialysis are arrhythmias due to electrolyte derangements, uremic pericarditis, and fluid overload due to severe congestive heart failure precipitated by suboptimal kidney function. After structural cardiac abnormalities, electrolyte (calcium, magnesium, and potassium) derangements are the most common arrhythmias. Metabolic acidosis and decreased renal excretion in chronic kidney disease or renal failure patients lead to potassium abnormalities. Iatrogenic causes in cardiac patients are an improper use of ACE inhibitors, angiotensin-receptor blockers, and aldosterone antagonists. In renal failure patients, elevated urea levels can also lead to uremic pericarditis. Patients with CKD and heart failure experience fluid retention, which leads to worsening heart failure and pulmonary edema.

Contraindications

Absolute contraindication to hemodialysis is the inability to secure vascular access, and relative contraindications include:

• Difficult vascular access
• Needle phobia
• Cardiac failure
• Coagulopathy

Modern techniques are employed in patients with extensive vascular disease to improve the establishment and salvaging of vascular access. Relative contraindications like needle aversion can be overcome by careful use of local anesthetics and nursing encouragement. Severe coagulopathy complicates the maintenance of anticoagulation in the extracorporeal circuit.

Where the patient can clearly express the wish to decline dialysis treatment, the provider is obliged to respect this decision. Nonetheless, the nephrologist must ensure adequate addressing of all reversible factors, such as unfounded fears about the dialysis process or a depressive illness clouding the judgment and requesting a psychiatric evaluation. In such patients, especially those with multiple comorbidities, a shift is made to conservative management using all proper treatments apart from dialysis.

Patients with unacceptable quality of life should be spared the discomfort of HD as survival on dialysis may be no longer with most of the additional time spent on having or recovering from dialysis sessions. Symptomatic treatment of ESRD and its complications can be done with medication and diet, such as pain management with analgesics. In addition, low doses of gabapentin or pregabalin can be used for severe itching and insomnia.

Equipment

Hemodialysis (HD) apparatus includes:

1. Blood circuit
2. Dialysis solution circuit

A dialyzer bridges these circuits. Side ports attached to the bloodlines are used for saline or heparin infusion, air entry detection, and pressure measurements. The dialysate is pumped through the dialysate compartment, separated from the blood compartment by the dialyzer's semi-permeable membrane. Regenerated cellulose, with its strongly hydrophilic nature, enables miniaturization of the dialyzer with lower membrane thickness.[3] Biocompatible synthetic membranes made of polysulfone provide a semi-permeable interface with lower complement cascade activation compared to the older bio-incompatible ones. The temperature and concentration of the dissolved components of the dialysis solution are regulated. A blood leak detector stops dialysis by detecting blood products in the outflow dialysate.

Blood Circuit

A spring-loaded roller pump moves blood through the dialyzer. Internal filtration (IF) enhanced hemodialysis requires no additional equipment like a roller pump and is more convenient than hemodiafiltration. The inflow bloodline or pre-pump segment connects the vascular access to the blood pump. It contains a saline infusion line, a sampling port, and a "pre-pump" pressure monitor. The sampling port is helpful for the collection of predialysis and post-dialysis blood. A "T" line primes the dialyzer circuit and rinses the blood compartment toward the end of the dialysis session. There is a post-pump pressure monitor as well, and a sudden rise in it indicates impending clotting of the bloodline or dialyzer. The heparin line delivers heparin at a constant rate throughout dialysis. A venous pressure alarm is attached to the venous line; however, it may not be reliably alert to an accidental venous line detachment. Therefore a sensor is used to detect a potential line separation in those with an increased likelihood of line separation (agitated/uncooperative patients with cognitive defects). The venous air trap chamber contains any air in the bloodline, which cuts off the power supply to the pump and stops dialysis, thus ensuring patient safety. A clamp below the drip chamber along the tubing returning blood to the patient is activated by the air present in it and snaps shut, stopping the blood pump.

The dialysis fluid circuit includes:

• A water purification system
• A proportionating system that mixes the water and concentrates and feeds it to the dialyzer
• Monitors, alarms, and ultrafiltration control with advanced control options

The standards for water purity in dialysis are defined by the Advancement of Medical Instrumentation (AAMI). The delivery system can be:

1. Central: A single apparatus combines with purified water to provide the dialysis solutions for the unit, supplied to each machine through pipes. This has the advantage of being more economical regarding the initial equipment and labor costs. However, it does not allow for individualization of dialysate composition and risks exposing many patients to complications arising from an error in the system.
2. Individual: Each machine proportions its dialysate concentrate and purified water.

Before the delivery of the dialysate to the dialyzer, correction for temperature by heating to 35–38 C followed by exposure to negative pressure for degassing is performed. Special attention must be paid to the osmolality of the dialysis solution, as a severely hyperosmolar solution can cause hypernatremia and other electrolyte disturbances. At the same time, a hypoosmolar solution can lead to rapid hemolysis, severe hyponatremia, and hyperkalemia. An alarm indicates any disturbance in the conductivity of the dialysate beyond 12 to 16 mS/cm and diverts the dialysate to the drain. Cold dialysate (less than 35 C) can cause hypothermia in an unconscious patient, while shivering occurs in a conscious patient. Dialysate temperature of more than 42°C causes blood protein denaturation and hemolysis.

The dialysis circuit has a temperature sensor that can bypass dialysate outside the set temperature range. Machines using the three-stream method- water, acid concentrate, and bicarbonate concentrate allow variation in the bicarbonate concentrate useful in acidotic patients, those with frank metabolic alkalosis, or patients at risk of developing respiratory alkalosis. The 'dry weight' probing approach helps evaluate dialysis adequacy and is associated with cardiovascular benefits. Aggressive fluid removal during intermittent dialysis causes cardiovascular stress and organ damage. Patients tend to tolerate higher UF rates earlier than later in a dialysis treatment, which is a better approach than a constant rate of fluid removal. Alternative fluid status assessment and non-invasive monitoring tools (e.g., ultrasound, blood volume monitoring, bioimpedance), clinical examination, and cardiac biomarkers (e.g., natriuretic peptides) are required to improve cardiovascular outcomes in high-risk patients. Homeostasis is maintained by adjusting the rate of salt and fluid removal during dialysis (ultrafiltration, dialysate sodium) and limiting salt intake and fluid gain in the interdialytic period. More precise and personalized handling of sodium and water can be done using feedback control tools and biosensors on the dialysis machine.[4]

Bicarbonate-buffered dialysate is preferred over acetate dialysate, which may lead to peripheral vasodilation and myocardial depression. However, bicarbonate-buffered dialysate still contains 3 to 5 mmol/l of acetate, which may be associated with increased academia, hypotension, and arrhythmia, particularly in critically ill patients. Online blood temperature and volume monitoring automatically adjust parameters using a biofeedback system. An adjustment follows a fall in circulating blood volume in ultrafiltration rate and dialysate [Na+], and blood temperature is maintained at a target value by thermal transfer control to and from the dialysate to prevent vasodilation and a drop in vascular resistance. High-dialysate calcium (1.75 mmol/l) contributed to greater hemodynamic stability in ESRD patients with cardiomyopathy undergoing intermittent hemodialysis. However, its use in the ICU setting is limited by the occurrence of hypercalcemia. Slower fluid and solute removal in lower efficiency modalities of acute RRT have improved hemodynamic stability with better blood pressure maintenance and reduced vasopressor requirements in patients undergoing continuous rather than intermittent hemodialysis. Further improvements in the design of dialyzers with a sharp cut-off membrane between low-molecular-weight proteins (LMWPs) and albumin, in addition to an adsorptive property for some LMWPs, need to be made. In addition, biocompatible membranes with lower complement cascade activation are necessary.

Wearable and implantable artificial kidneys are the future of hemodialysis, with lower operational costs helping overcome the infrastructural barriers to providing self-care treatment for renal failure. They employ a sorbent-based dialysis regenerative system called recirculating dialysate (REDY) in which the solute wastes from the spent dialysate pass-through columns containing urease. Urea gets hydrolyzed into ammonia and carbon dioxide. Hydration with water molecules produces ammonium and bicarbonate ions. Ammonium serves as a dietary acid remover and binds nitrogen from the dialysate. The dialysate then passes sequentially over the cation and anion exchange columns, during which cations like potassium, calcium, and magnesium, as well as organic toxins like phosphates and sulfates, are removed. Finally, the dialysate is recharged with calcium and magnesium and returned to flow through the dialyzer again. These battery-operated devices use sorbent cartridges and can be worn like a purse, belt, or vest.

An implantable artificial kidney employs silicon nanotechnology and tissue engineering to produce a surgically implanted device that mimics a native kidney. It includes a high-efficiency filter, the hemocartridge made of microchips, and a bioreactor of cultured epithelial cells of the renal tubule harvested from the cadaveric kidney, the biocartridge. The ultrafiltrate produced closely resembles urine. It prevents electrical pumps as the patient's blood pressure drives the device. No dialysate is needed since salt and water reabsorption by the bio cartridge helps maintain a neutral fluid balance while eliminating concentrated wastes. These devices provide gradual, continuous ultrafiltration therapy, which will reduce intradialytic hypotension and cardiac disease of dialysis.[5]

Personnel

A dialysis care team is an interprofessional group of qualified individuals contributing to holistic patient management and a smooth transition to a dialysis-dependent life. Nephrologists are team leaders with expertise in treating renal conditions. They educate patients about disease progression and measures to slow the decline in renal function and encourage their participation in management decisions.

Advanced providers such as a nurse and a provider assistant collaborate with nephrologists in managing kidney patients at medical offices and the dialysis unit. A nephrology nurse is specialized in assessing dialysis patients, assuring proper administration of medications and treatment, and overseeing the dialysis process. They also supervise home programs training patients and their care partners in administering self-dialysis modalities like home hemodialysis and continuous ambulatory peritoneal dialysis (CAPD). Renal dietitian-help plan meals and tailor the diet to meet each patient's unique needs. They review dialysis adequacy, rehabilitation, bone management, and anemia management. Nephrology social workers counsel patients and their families to help them cope with renal disease. They can help make lifestyle changes, identify sources of emotional support, identify services provided by agencies to meet patients' needs, and improve the quality of life.

The patient care technician performs the dialysis treatment and monitors patients throughout, while biomedical technicians maintain the machines and water quality at the dialysis center. The vascular access care team includes a vascular access surgeon who creates and maintains dialysis access. The radiologist's imaging helps plan access surgery. The interventional radiologist places a catheter, repairs the fistula, and treats vascular thrombosis. The access coordinator reviews the access history, plans treatment, follows up to ensure that the appropriate treatment was received, and records the information. Billing personnel can answer questions about insurance coverage, billing, or payment.

The National Kidney Foundation is a valuable member of the healthcare team. It supports research to manage renal disease, provides the community with valuable information about kidney disease, management options, diet, and rehabilitation, and offers programs and services for patients with kidney disease.

However, the most important members of this dialysis care team are the patients themselves and their families or caregivers.

Preparation

The procedures for the preparation and their complications account for 25% of chronic uremia hospital admissions. The gold standard is the distal AV fistula.[6] The alternatives are synthetic grafts and tunneled central venous catheters after a patient’s superficial veins have been exhausted. The recommended current strategy is to permanently catheterize only those patients on chronic hemodialysis who have exhausted their peripheral vascular beds. Preparation of appropriate infrastructure for home hemodialysis must be undertaken only after checking out any legal restrictions (central/local government) on the use of a dwelling for the purpose. Ensure that the prerequisites are met and that the home has a sound structure unaffected by dampness, mold, or high environmental pollution, along with stable electricity and ample water supply. Provisions must be made for RO purification and wastewater, dialysate, and biomedical waste disposal.

Community house hemodialysis provides a homelike non-institutional setting with flexible scheduling similar to home HD. Each patient has a separate space with a machine bay, dialysis equipment, and other consumables and is responsible for their dialysis. For those who dialyze more frequently (five or more times a week), a dedicated machine and space in the community HD location are the best, while those on a thrice-a-week or alternate-day regimen can share a machine. The home HD program is responsible for infrastructure, equipment, and community house maintenance.[7]

Patients seeking nocturnal dialysis are limited to their bedrooms, while those fearing unintentional needle dislodgement may prefer daytime dialysis. Those with larger, more static HD machines have limited options for machine placement. At the same time, mobile batch dialysis equipment permits a change of location as long as the appropriate peripheral equipment and outlets are in place. The provision and undertaking of dialysis at home involves sharing and division of responsibilities between the home HD program and the patient. Both parties, as well as care providers, must understand their responsibilities. An agreement should be documented as patient contracts or in-unit policies and procedures. The liability towards installation and maintenance should be made clear at the beginning.

Technique or Treatment

In the United States, approximately 430,000 patients are dependent on hemodialysis. Options for access include catheters, arteriovenous fistulas (AVFs), and arteriovenous grafts (AVGs).[8][9][10][11] A 15 gauge needle is inserted to access circulation. The "fistula first" initiative encourages the creation of an arteriovenous fistula in most patients to provide reliable access to the circulation. However, most patients have an arteriovenous graft in which polytetrafluoroethylene prosthetic is interposed between an artery and vein. Blood is pumped through the dialyzer at a rate of 300 to 500 ml/min while dialysate flows in a counter-current direction at 500 to 800 ml/min. The negative hydrostatic pressure on the dialysate side is used to achieve adequate fluid removal or ultrafiltration. Dialysis targets depend on the urea reduction ratio, that is, the fraction of blood urea nitrogen reduced per hemodialysis session, ideally 65 to 70%. Hemodialysis dose should be individualized after accounting for the adequacy of ultrafiltration, control of hyperkalemia, hyperphosphatemia, acidosis, and fluid removal.[12]

Dialysis modality was an independent predictor of illness intrusion, with more significant intrusion felt in those on hemodialysis than peritoneal dialysis, which is considered more suitable for older patients with multiple comorbidities. The six-times-a-week hemodialysis regimen was associated with improved control of hypertension, hyperphosphatemia, and reduced left ventricular mass with enhanced self-reported physical health compared to the thrice-weekly regimen. However, a significant rise in mortality and hospitalization for heart failure was noted following the longer intradialytic intervals over the dialysis weekend.

Home hemodialysis is done 3 to 6 nights per week for 6-8 hours each for those who prefer it for lifestyle considerations. It is associated with a raised risk of vascular access complications, caregiver burden, and rapid decline in residual kidney function. Long frequent hemodialysis, either in-center or at home, is recommended during pregnancy in a female with end-stage renal disease. In case of low residual renal function, choose thrice-weekly hemodialysis, with each session lasting for a minimum of three hours. Additional or more extended sessions are considered for patients with significant weight gains, poorly controlled blood pressure, high ultrafiltration rates, poor metabolic control, or difficulty achieving dry weight. The chosen ultrafiltration rate for each session should allow for an optimal balance between achieving euvolemia, solute clearance, and adequate blood pressure control with minimal hemodynamic instability and intradialytic symptoms. Dialysis patients have a reduced health-related quality of life (HRQoL) associated with increased morbidity and mortality. The HRQoL is of the following kinds:

1. Physical: It is defined by limited or impaired mobility and role limitations, manifesting as sleep disorders (obstructive sleep apnea, fatigue, restless legs).
2. Mental: It encompasses depressive thinking and anxiety. Intensive hemodialysis (HD) positively impacts HRQoL by increasing the physical and mental component scores. It is also associated with significantly reduced post-dialysis recovery time.[13]

Patients requiring dialysis while on the go can make an appointment at transient centers (local dialysis centers) 6 to 8 weeks in advance to ensure their place. The patient's usual dialysis center needs to pass information to the transient center about the patient's medical history, bloodwork and treatment records, a list of medications, insurance information, and any special requirements.

Complications

The most common complications associated with hemodialysis are:

• Intradialytic hypotension: This causes poor long-term outcomes due to increased mortality and increased rate of regional wall motion abnormalities during dialysis, known as myocardial stunning. A nadir systolic BP lower than 90 mmHg strongly correlates with mortality. It usually presents as dizziness, light-headedness, nausea, or subtle symptoms. Management revolves around maintaining the patient in the Trendelenburg position and rapidly administering a 100 mL bolus of normal saline through the bloodline. Reduce the ultrafiltration rate and observe the patient until vitals have stabilized.
• Muscle cramps: The pathogenesis is unknown. Hypotension, high ultrafiltration rate, hypovolemia, and low-sodium dialysis solution predispose to cramps. These factors trigger vasoconstriction and muscle hypo-perfusion, with secondary impairment of muscle relaxation. When occurring concomitantly with hypotension, treatment with 0.9% saline is effective. Forced stretching of the muscle involved could provide relief.

Some reactions are medical emergencies and must be managed by an immediate stopping of dialysis, clamping of lines, and supportive care followed by definitive care.[14] Examples of such complications are:

• Dialysis disequilibrium syndrome: This is more common in patients during or soon after their first treatment. It is a clinical syndrome characterized by neurologic deterioration, restlessness, mental confusion, headache, occasional muscle twitching, and coma. It occurs due to a substantial gradient between the urea concentrations in the CSF and blood that causes water movement into the central nervous system (CNS), resulting in raised intracranial pressure. Patients undergoing fast dialysis develop seizures and cerebral edema more often. A reasonable goal of urea concentration reduction is 40% over two hours, URR of 0.4. Adding an osmotic agent to the blood could prevent the gradient from forming. Sodium, mannitol, high glucose dialysate, and glycerol are usually added. Setting the dialysate’s sodium concentration higher throughout the treatment may be beneficial.[15][16]
• Dialyzer reactions: Anaphylactic type A reactions present with dyspnea, increased body and local temperature at the fistula site, a feeling of impending doom, itching, urticaria, coryza, watery eyes, abdominal cramping, and diarrhea. Symptoms may begin anytime during the first 30 minutes following dialysis due to hypersensitivity to ethylene oxide used to sterilize dialyzers. Management includes intravenous antihistamines, steroids, and epinephrine. Proper rinsing of dialyzers before use eliminates residual allergens and helps prevent them. Nonspecific type B dialyzer reactions cause chest or back pain 20 to 40 minutes after commencing dialysis, attributable to complement activation. Trying a different dialyzer membrane may help prevent it.
• Hemolysis: Acute hemolysis during dialysis is a medical emergency indicated by the port-wine appearance in the venous blood line, a marked fall in the hematocrit, and a pink-colored plasma centrifuged blood sample. The patient should be evaluated by hematologic investigations and kept under observation for delayed hemolysis. A dialysate sample must be investigated to find the cause.
• Air embolism: This is a fatal complication with foam noted in the dialyzer’s venous blood line. A churning sound may be heard during chest auscultation. Place the patient in a left lateral recumbent position, administer 100% oxygen by mask and aspirate air from the cardiac chambers with a percutaneously inserted needle or cardiac catheterization.
• Other nonspecific complications include nausea and vomiting (10%), headache (70%), chest and back pain (1% to 4%), and itching. These are probably related to hypotension or could be an early manifestation of disequilibrium syndrome. Treating the associated hypotension resolves the symptoms. A single predialysis dose of 5 to 10 mg metoclopramide is sufficient. Acetaminophen given during dialysis can help manage the headache. Switching to a different type of dialyzer membrane could reduce itching caused by low-grade hypersensitivity to blood circuit components. Vascular access dysfunction, most commonly stenosis of arteriovenous access, is the strongest determinant of the quality of life of a dialysis patient. There are reduced blood flow and risk for thrombosis.[17] The formation of a catheter-related fibro-epithelial sheath also hampers blood flow. Urokinase instillation, endovascular catheter stripping, or replacement of the indwelling dialysis catheter in a subcutaneous tunnel re-establish access.[18][19]
• Precautions for vascular access: Do not cause additional trauma to the arm at the access site; avoid wearing tight clothes/jewelry, carrying heavy items, and sleeping on the arm. Avoid blood collection or measurement of BP on this arm. Rotate the site of needle insertion on the access. Use gentle pressure to arrest bleeding after needle removal. Bleeding can be stopped by applying gentle pressure; the patient should be educated to call a health care provider for prolonged/profuse bleeding lasting more than 30 minutes. Bleeding is due to the use of heparin in dialysis patients and can be treated efficiently using protamine sulfate. Monitoring venous and arterial pressures to detect a line separation, securing and taping needles, using wetness detectors for blood and dialysate leaks, and closed connector devices for tubing junctions. Periodic local site examination for any signs of infection like redness, warmth, and pain must be carried out. In case of loss of normal bruit, access site clotting should be ruled out to prevent limb ischemia.

Dialysis is used to treat electrolyte imbalance; however, it can also cause it. Hyperkalemia is the most common and clinically significant complication in non-compliant patients besides hypermagnesemia, hyponatremia, and hypocalcemia.[20] A cardiac arrest is twice as likely in HD as in PD patients three months after dialysis initiation. Sudden cardiac deaths are most likely during the first two months after the initiation of hemodialysis. The predominant arrhythmias identified are ventricular fibrillation (66%), pulseless electrical activity, and asystole. In the vascular access process, death may occur from cardiac arrhythmias, pulmonary edema, or contrast medium reaction.[17]

Clinical Significance

Chronic kidney disease (CKD) patients needing dialysis have a build-up of uremic retention solutes, like asymmetric dimethylarginine (ADMA), indoxyl sulfate, and p-cresol, that could have proatherogenic properties. Failing kidneys produce lower amounts of cardiovascular disease and atherogenesis inhibitors like renalase, a soluble monoamine oxidase that regulates blood pressure. In addition, dialysis patients experience a state of chronic inflammation. Biomarkers like CRP, fibrinogen, pentraxin 3 (PTX3), interleukin 6 (IL-6), white blood cell count, and the presence of endothelial cells in circulation independently predict mortality in CKD patients as they indicate endothelial dysfunction.

Dialysis patients develop arterial sclerosis and secondary stiffening that commonly causes isolated systolic hypertension with raised pulse pressure. Intradialytic hypertension occurs in more chronically volume-overloaded patients with intradialytic vascular resistance surges attributable to acute changes in endothelial cell function during dialysis. Reducing dialysate sodium and including poorly dialyzed antihypertensives like carvedilol in the prescription cause improvement.[21]

Elevated lipoprotein (a) levels are associated with increased cardiovascular disease mortality. Cardiovascular diseases (CVD) and renal disease are closely associated, and patients having a history of both have higher morbidity and mortality. The presence of chronic kidney disease compounds increases the likelihood of CVD. Cardiovascular morbidity, mortality, and all-cause mortality are predicted by a fall in the estimated glomerular filtration rate (eGFR) and albuminuria. Albuminuria is a subtle indicator of kidney dysfunction, microvasculature health, and endothelial function. The early identification and management of the cardiovascular risk factors in a patient with mildly reduced eGFR are imperative to ensuring that the patient does not die from cardiovascular disease before requiring renal replacement therapy.

Cardiovascular pathologies in CKD range from generalized vasculopathy, vascular noncompliance, and calcification to left ventricular hypertrophy (LVH). The diseases that closely resemble congestive heart failure and fluid overload should be ruled out—for example, acute respiratory distress syndrome, bacterial pneumonia, cirrhosis, community-acquired pneumonia, and pulmonary fibrosis. Non-cardiogenic causes of fluid overload often lack jugular venous distention and an S3 gallop. Measuring left ventricular pressure (LVP) through the pulmonary capillary wedge pressure (PCWP) helps distinguish between cardiogenic and non-cardiogenic pulmonary edema. PCWP is almost always low in those with non-cardiogenic pulmonary edema. Other conditions considered among the differentials are pulmonary embolism, angina, coronary artery disease, aortic dissection, structural heart disease, hyperthyroidism, stress, and excess caffeine and nicotine, besides esophageal disorders like esophagitis, esophageal rupture, and esophageal spasm. The concurrent decrease in the functioning of both kidneys and the heart makes dialysis a critical intervention for preventing and treating life-threatening cardiac conditions.

Sustained high levels of FGF-23 lead to atrial fibrillation (AF), LVH, and mortality. Other factors contributing to mortality risk are hyperphosphatemia, followed by hypercalcemia and parathyroid abnormalities. Mineral metabolism disorders account for about 17% of overall mortality in HD patients. In dialysis patients, early-onset extensive vascular calcification (coronary arteries) occurs besides calcification of aortic and mitral valves leading to progressive stenosis, morbidity, and mortality. Hemodialysis sessions are associated with cardiac arrhythmias like atrial fibrillation. Peripheral arterial disease (PAD) is seen more commonly in those dialysis patients with comorbidities like diabetes/preexisting atherosclerosis. The risk is proportional to the time on dialysis. Patients undergoing dialysis have the stroke risk thrice.

Dialysis and COVID

A French study assessed the potential risk of the spread of the coronavirus through continuous renal replacement therapy (CRRT) and found it to be minimal. The plasma from the patients involved in the study was positive for SARS-CoV-2 RNA. However, the dialysis effluent did not contain the viral RNA. Therefore the routine use of a viral filter is not supported. Instead, the primary focus should be educating healthcare workers on the preventative aspects of limiting the viral spread during invasive procedures.

Enhancing Healthcare Team Outcomes

A simple nephrology office consultation may be insufficient in equipping patients with knowledge about CKD. Additional care provided by a pre-dialysis interprofessional team produces better biochemical results, more planned dialysis initiations with less hospitalization, with the possibility of improved survival rates. Unfortunately, 36% of new ESRD patients in the United States in 2015 had not received any nephrology care before starting. This led to a more extended initial hospital stay, complications, and death.

The timely creation of dialysis access; and, where feasible, preparation for renal transplantation pre-emptively (before initiating dialysis) provides the best potential rehabilitation since dialysis replaces only some of the kidney's filtration functions and not the endocrine and anti-inflammatory effects. In addition, consistent pre-dialysis care has been associated with better outcomes and lower healthcare expenditure. Therefore, the best approach is to transfer patients to a multidisciplinary team to identify a declining GFR at least 12 months before dialysis. The start date is determined by extrapolating a trend line of the eGFR until it reaches 10 ml/min/1.73 m^2.

All patients are referred for multidisciplinary and interprofessional care when the eGFR reaches 15 ml/min/1.73 m^2, as concurrent illnesses may cause a sudden drop in renal function, thus creating the need for emergent dialysis. Group education session allows fellow patients to educate new patients. Support groups provide much-needed reassurance to the patients and their families, helping them cope with the demands of ESRD. The team ideally includes a nurse educator, physical therapist, occupational therapist, dietician, social worker, pharmacist, and sometimes a trained peer-support volunteer. Each of these team members must contribute from their expertise but also include input and communication from other team members in helping to guide patient therapy. Having an interprofessional liaison for dialysis access has proven very effective in extending the patency of the fistula and reducing morbidity and mortality.[22][23][24][25]

Pharmacists must help manage the patient's medication regimen, considering which drugs are dialyzable and which are not, and help guide the dosing of these drugs. They will work with both the nurse and prescriber to achieve safe medication therapy in the setting of dialysis.

A controlled trial in California highlighted the value of social worker inputs to the pre-dialysis program in improving gainful employment. These patients had a better quality of life, a more positive attitude to work, and greater self-esteem. National organizations like the National Kidney Foundation provide web-based patient information besides printed and audiovisual material. A cardiology referral for echocardiography is mandatory in all dialysis patients, 1 to 3 months after dialysis initiation, on an inter-dialytic day, and at 3-year intervals after that. Accurate LV systolic function assessment is a determinant of CVD and mortality.

Nursing, Allied Health, and Interprofessional Team Interventions

Home hemodialysis causes additional caregiver/patient burden. However, imparting adequate pre-dialysis education, motivation, and training of patients and caregivers, assisted cannulation, home visits by nurses, and an organized framework for providing nursing, technical support, and respite care for patients have been shown to improve the adoption of home HD.

Sticking to a healthy diet has been shown to improve outcomes in patients undergoing hemodialysis.[26] A study has indicated that text messaging to advise dialysis patients about healthy eating habits periodically has improved adherence to dietary recommendations and decreased the need for phosphate binder therapy. The reminders regarding the intake of potassium, phosphorus, sodium, and fluids, besides general nutrition and lifestyle tips, include:

• Consumption of fresh foods to cut down on phosphate intake, present abundantly in prepackaged food
• Read food labels, and be aware of the contents. Choose foods with less than 400 mg sodium/100 g
• Pasta, rice, and sweet potato should be consumed 3–4 times a week instead of a regular potato to regulate potassium intake

Nursing, Allied Health, and Interprofessional Team Monitoring

Commencing home hemodialysis creates unique psychosocial issues affecting the patient and care partner. The home HD health care team must provide proactive inter-professional support, respite care, travel support, peer support, and financial support. Improper redressal of these aspects could cause patients to return to in-center HD. Some centers provide real-time monitoring of home HD treatments, and a panic button/alarm may be present to contact the local paramedic unit.[27]