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 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, to buy time until a kidney transplant can be carried out, or for sustaining 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 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 RRT incidence. All patients who are 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 who are provided with the 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 help keep track of the population dependent on RRT. They also include hospital-specific information, safety, and quality reporting and provide resources for clinical research. Access to dialysis is affected by sociocultural and socioeconomic factors. ESRD is disproportionately higher in African Americans and CKD among the White population. ESRD disease burden is attributed to diabetes mellitus (45%) and hypertension (30%) besides rarer causes like polycystic kidney disease, obstructive uropathy, 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 its impact on income or the availability of health insurance. Indigenous people in Australia, New Zealand, 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)

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. It is not advisable to assign an arbitrary urea nitrogen or creatinine level for dialysis initiation 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 and/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 an increased risk of mortality. 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 '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. Clinician'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 both dialysis and non-dialysis requiring CKD patients showed a 17% reduction in cardiovascular death and major cardiovascular events with simvastatin-ezetimibe treatment. Conventional cardioprotective strategies such as beta-blockers, aspirin, 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.

Dialysis involves 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. 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 in 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 rate of diffusion 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 the conditions of flow 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 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 that 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 is equal to 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.

Hemodialysis initiation is needed for acute illness associated with AKI, life-threatening hyperkalemia, refractory acidosis, hypervolemia causing end-organ complications (e.g., pulmonary edema), or 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. ARRT enhances cytokine removal in high-cytokine states like sepsis. There is a potential for 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.[1]

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, a progressive deterioration in nutritional status despite dietary intervention or impairment in cognition. It 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. Potassium abnormalities arise from acidosis (due to intercellular shift) and decreased renal excretion in chronic kidney disease or renal failure patients. 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 of heart failure and pulmonary edema.

Patients usually present with shortness of breath, exertional dyspnea, and paroxysmal nocturnal dyspnea. Most are known cases of CHF experiencing fluid overload. Other signs and symptoms are nausea, bloating, edema, cough, fatigue, and weight gain. Patients with arrhythmia come with anxiety, palpitations, lightheadedness, and syncope due to reduced cerebral perfusion. Chest pain may be present but is usually due to ischemia or tachycardia, causing demand ischemia. Pleuritic chest pain with radiation to the trapezius left shoulder or arm is seen with the onset of pericarditis besides fever, bradycardia, and hypotension due to autonomic inhibition. The pain is worse in the supine position and gets relieved on leaning forward.

On physical examination, patients may be relaxed or dyspneic depending on the amount of fluid and New York Heart Association stage of congestive heart failure. Many patients improve with little rest after exercise. Patients may have ascites associated with rales at the lung bases heard associated with wheezing and frothy red sputum. Jugular venous distension with hepato-jugular reflux can also be present. A third heart sound (S3) due to the rushing of extra fluid in the left ventricle may also be heard. The pulse may be irregular or absent. Hypotension, tachypnea, confusion, and diaphoresis can be present.

A transient pericardial friction rub is always pathognomonic for acute pericarditis. Auscultating the apex or left sternal edge during the expiration with the patient leaning forward increases the likelihood of auscultating the pericardial rub.

Absolute contraindication to hemodialysis is the inability to secure vascular access, and relative contraindications involve difficult vascular access, needle phobia, cardiac failure, and 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 is able to clearly express the wish to decline dialysis treatment, the physician is under an obligation to respect this decision. Nonetheless, the nephrologist must ensure adequate addressing of all reversible factors, such as unfounded fears about the process of dialysis or a depressive illness clouding the judgment and request for a psychiatric evaluation. In such patients, especially those with multiple comorbidities, a shift is made to conservative management using all acceptable treatment 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. Low doses of gabapentin or pregabalin can be used for severe itching and insomnia.

Hemodialysis (HD) apparatus includes:

1. Blood circuit
2. Dialysis solution circuit

These circuits are bridged by a dialyzer. 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.[2] 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 on 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 blood line 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 useful for the collection of predialysis and post-dialysis blood. A "T" line primes the dialyzer circuit and rinses the blood compartment towards 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 blood line or dialyzer. The heparin line delivers heparin at a constant rate throughout dialysis. There is a venous pressure alarm that 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). Any air in the blood line is contained by the venous air trap chamber, 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 air present in it and snaps shut, stopping the blood pump.

The dialysis fluid circuit includes:

• A water purification system
• A proportionating system which mixes the water and concentrates and feeds it to the dialyzer
• Monitors, alarms, 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 all of the dialysis solutions for the unit, supplied to each machine through pipes. This has the advantage of being more economical in terms of the initial equipment and labor costs. However, it does not allow for individualization of dialysate composition and has the risk of exposing many patients to the 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. While a hypoosmolar one 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 that is 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 assessment, cardiac biomarkers (e.g., natriuretic peptides) are required to better the cardiovascular outcome in high-risk patients. Homeostasis is maintained by adjusting the rate of salt and fluid removal during dialysis (ultrafiltration, dialysate sodium) as well as by 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.[3] 

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 acetemia, hypotension, and arrhythmia, particularly in critically ill patients. Online blood temperature and volume monitoring are automatically adjusted parameters using a biofeedback system. A fall in circulating blood volume is followed by an adjustment in UFR 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 drop in vascular resistance. High-dialysate calcium (1.75 mmol/l) contributed to greater hemodynamic stability in ESRD patients with cardiomyopathy undergoing intermittent hemodialysis. 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 BP 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. Biocompatible membranes with lower complement cascade activation are necessary.

Wearable and implantable artificial kidneys are the future of hemodialysis with lower operational costs that help overcome the infrastructural barriers to the provision of self-care treatment of 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 in sulfates, are removed. The dialysate is then 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 a 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 obviates the need for electrical pumps as the device is driven by the patient's blood pressure. 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 ameliorate intradialytic hypotension and cardiac disease of dialysis.[4]