Hemodialysis

Anatomy and Physiology

Dialysis involves the removal of solutes and excess fluid across a semipermeable membrane by the following 3 primary mechanisms:

1. Diffusion: This involves the movement of dissolved particles from an area of high concentration to a low concentration across a semipermeable membrane. Diffusion promotes the movement of smaller particles and occurs most rapidly when the concentration gradient across the semipermeable membrane is highest. Increasing the dialyzer size, dialysate flow, or the blood flow increases the rate of diffusion.
2. Convection: This mechanism occurs when dissolved particles pass across a semipermeable membrane due to a pressure gradient. Larger particles are restricted, while particles that are smaller than the pores of the membrane pass freely. The removed solution is isotonic to the original, as the particles and water move together. 
3. Ultrafiltration: The movement of water across a semipermeable membrane due to hydrostatic pressure. Convection occurs with ultrafiltration. 

Dialysate solution is a sterile fluid that contains sodium, buffer (eg, bicarbonate), chloride, potassium, magnesium, calcium, and dextrose. Dialysate usually contains potassium levels lower than 4.0 mEq/L and no phosphate, as these are elevated in patients with renal failure. The osmolality of the solution is maintained close to the osmolality of blood to prevent hemolysis. 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.

Modern hollow-fiber dialyzers are plastic cartridges containing thousands of thin capillary fibers with microscopic pores that allow water and small molecules to pass through. Dialyzers differ in surface area, permeability, volume required to prime the cartridge, and membrane composition. Selecting specific dialyzer characteristics enables tailoring the dialysis prescription to the patient's clinical needs.

During dialysis, a concentration gradient is maintained (and equilibrium avoided) by continuously refilling the dialyzer with fresh dialysate and replacing dialyzed blood 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 was a parameter introduced by Gotch and Sargent through their National Cooperative Dialysis Study.[11] Kt/V 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 less than 0.8 was associated with higher morbidity or treatment failure, whereas a Kt/V of more than 1.0 was associated with improved outcomes. A Kt/V of 1.0 implies that the total blood volume cleared during a session equals the urea distribution volume.

Indications

Hemodialysis initiation is needed in patients with the following indications:

• Uremia with complications, eg, encephalopathy, pericarditis, neuropathy, seizures, platelet dysfunction with severe bleeding, intractable nausea or vomiting
• Toxic ingestion (eg, salicylates, ethylene glycol, methanol, lithium, metformin, barbiturates) or metabolic derangements leading to the overproduction of endogenous toxins (eg, ammonia) [12][13][14][15]
• Dyselectrolytemia, especially hyperkalemia with plasma potassium concentration greater than 6.5 mEq/L or hyperkalemia with electrocardiogram (ECG) changes
• Refractory acidosis (pH <7.2 and refractory to bicarbonate or unable to give bicarbonate due to volume overload) or symptomatic acidosis (eg, arrhythmias)
• Fluid overload refractory to diuretic therapy

The IHD system allows for more rapid ultrafiltration than any other renal replacement modality, making it the preferred choice for managing severe volume overload. Patient tolerance of rapid fluid removal may limit its use. CRRT provides continuous ultrafiltration for critically ill patients, supporting cardiovascular stability and maintaining metabolic balance. Although CRRT removes solutes and fluids less efficiently than IHD, its continuous delivery prevents the fluctuations associated with intermittent therapy, allowing consistent administration of medications, nutrition, and blood products while preserving overall stability. CRRT can also serve as an adjunctive therapy for cytokine release syndrome unresponsive to tocilizumab or corticosteroids by facilitating the removal of proinflammatory cytokines, including IL-6, from the circulation.[16]

The National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (KDOQI) 2015 update offers guidelines for hemodialysis adequacy. Patients reaching CKD stage 4 (eGFR 15–29 mL/min/1.73 m²) or those approaching maintenance dialysis should receive counseling on kidney failure and available treatment options, including kidney transplantation, home or in-center hemodialysis, peritoneal dialysis, or conservative management. Education should also extend to family members and caregivers. Initiation of maintenance dialysis should be based on the presence of signs or symptoms of kidney failure, eg, pruritus, acid-base or electrolyte abnormalities, serositis, volume or blood pressure dysregulation, progressive nutritional deterioration despite dietary intervention, or cognitive impairment, rather than on kidney function alone in asymptomatic individuals.[17]

Contraindications

An 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 salvage of vascular access. Relative contraindications, eg, needle aversion, can be overcome by careful use of local anesthetics and nursing encouragement. Severe coagulopathy complicates anticoagulation maintenance in the extracorporeal circuit.

When the patient clearly expresses a wish to decline dialysis treatment, the clinician is obliged to respect that decision. Nonetheless, the nephrologist must ensure adequate addressing of all reversible factors, eg, unfounded fears about the dialysis process or a depressive illness clouding judgment. In competent patients refusing dialysis, especially those with multiple comorbidities, a shift is made to conservative management using all proper treatments apart from dialysis.

In patients with an unacceptably poor quality of life, the initiation of hemodialysis may offer limited survival benefit, with a substantial proportion of their remaining life spent undergoing or recovering from dialysis sessions. Symptoms of these patients can be managed with medication (ie, analgesics) and diet. In addition, low doses of gabapentin or pregabalin can be used for severe itching and insomnia.

Equipment

The hemodialysis circuit consists of 4 components (see Image. Types of Hemodialysis Access).[18] 

Prefilter Segment

The prefilter segment carries blood from the patient's vascular access to the hemofilter. This portion of the circuit includes the blood tubing, a blood pump, and pressure sensors. Blood is aspirated into the prefilter circuit by the negative pressure generated by the blood pump, which is continuously monitored by an arterial access pressure sensor. The pump then propels blood through the hemofilter by creating positive pressure downstream of the pump. The combined effects of pump output and filter resistance are monitored by a prefilter pressure sensor positioned between the blood pump and the hemofilter. Internal filtration–enhanced hemodialysis (IFEHD), which uses an enhanced internal filtration dialyzer, may offer greater convenience than conventional hemodiafiltration therapies by eliminating the need for additional equipment (eg, a roller pump).[19]

Additionally, several auxiliary subcircuits may be connected to the prefilter segment, eg, a pre-blood pump infusion line, with its inlet located close to the vascular access, commonly used for citrate infusion when regional anticoagulation is employed. Another is a prefilter infusion pump circuit situated between the blood pump and the hemofilter, through which replacement fluid is delivered. A heparin infusion line is also integrated into this prefilter section of the circuit.

Dialysis Membrane or Hemofilte

The dialysis membrane or hemofilter is the component of the circuit through which solute and water are removed by convection, diffusion, or a combination of both, depending on the selected treatment modality. Blood enters and exits the cartridge through ports located at either end, while 2 additional lateral ports are used for dialysate inflow and effluent drainage; effluent pressure is continuously monitored by a sensor positioned between the filter and the effluent pump.

The hemofilter is a cylindrical cartridge containing bundles of semipermeable hollow capillary fibers that permit the transfer of solutes and fluid between the blood and surrounding compartments. Hemofilter membranes are advanced synthetic materials, primarily polysulfone (PSU), polyarylethersulfone (PAES), and modified acrylonitrile copolymers (AN69/AN69ST). The hollow fibers typically have an internal diameter of approximately 200 μm and a wall thickness of about 30 μm.[20][21] Membrane molecular weight cut-off varies by filter type. Dialysate and effluent flow around the exterior of these fibers. When convection alone is employed, the solute composition of the effluent closely mirrors that of plasma water entering the filter. In contrast, dialysate use establishes concentration gradients that facilitate the diffusive clearance of small solutes between blood and dialysate.

Before dialysate is delivered to the dialyzer, it is temperature-adjusted by heating to approximately 35 °C to 38 °C and then subjected to negative pressure to remove dissolved gases. Careful monitoring of dialysate osmolality is essential, as excessively hyperosmolar dialysate solutions may lead to hypernatremia and other electrolyte abnormalities. In contrast, hypo-osmolar solutions can precipitate rapid hemolysis, profound hyponatremia, and hyperkalemia. Dialysate temperatures below 35 °C may cause hypothermia in unconscious patients and shivering in conscious individuals, while temperatures exceeding 42 °C can lead to blood protein denaturation and hemolysis.

Postfilter Segment

The postfilter segment carries dialysed blood back to the patient. This portion of the circuit may include a postfilter infusion pump for administering postdilution replacement fluid and a venous air-removal chamber equipped with an air or bubble detector and an automatic blood-line clamp. Its primary role is to ensure patient safety, specifically by preventing accidental air entry into the circulation.[22] Additionally, an outflow pressure sensor is typically located within the bubble trap to monitor the venous return pressure. This measurement is critical for detecting circuit disconnections, as a sudden loss of resistance results in a pressure drop that triggers high-priority alarms and automatically ceases the blood pump.

Waste Fluid Circuits

Circuits carrying waste fluids contain the waste products. They can be measured for urea and other toxins (along with urine output, if any) to estimate the clearance of a particular substance further.

Future Directions

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 regenerative dialysis system called recirculating dialysate (REDY), in which solute waste from the spent dialysate passes 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, eg, potassium, calcium, and magnesium, as well as organic toxins, eg, 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 utilizes silicon nanotechnology and tissue engineering to create a surgically implantable device that mimics the function of a native kidney. An implantable artificial kidney includes a high-efficiency filter, a hemocartridge containing microchips, and a bioreactor containing cultured renal tubular epithelial cells harvested from cadaveric kidneys, known as the biocartridge. The ultrafiltrate produced closely resembles urine. It avoids electrical pumps as the patient's blood pressure drives the device. No dialysate is needed, as the bio cartridge maintains a neutral fluid balance by reabsorbing salt and water while eliminating concentrated waste products. These devices provide gradual, continuous ultrafiltration therapy, which will reduce intradialytic hypotension and cardiac disease of dialysis.[23]

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 the treatment of 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 practitioners, eg, nurses and medical assistants, collaborate with nephrologists in managing kidney patients at medical offices and the dialysis unit. A nephrology nurse specializes in assessing dialysis patients, ensuring proper medication administration and treatment, and overseeing the dialysis process. They also supervise home programs, training patients and their care partners in administering self-dialysis modalities, eg, home hemodialysis and continuous ambulatory peritoneal dialysis (CAPD). A renal dietitian helps 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 manage the challenges of renal disease. They can help individuals make lifestyle changes, identify sources of emotional support, locate services provided by agencies to meet patients' needs, and enhance 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. Pharmacists play a central role in managing medication regimens by identifying dialyzable drugs, adjusting dosing, and collaborating closely with nurses and prescribers to maintain medication safety.

A controlled trial in California demonstrated that social worker involvement in predialysis programs improved employment outcomes, quality of life, work attitudes, and self-esteem. National organizations, including the National Kidney Foundation, support patient education through web-based, printed, and audiovisual resources. Cardiology referral for echocardiography remains mandatory for all dialysis patients within 1 to 3 months of initiation, on an interdialytic day, and every 3 years thereafter, as accurate assessment of left ventricular systolic function strongly predicts cardiovascular disease and mortality. Furthermore, the National Kidney Foundation is a valuable member of the healthcare team, supporting research to manage renal disease, providing the community with valuable information about kidney disease, management options, diet, and rehabilitation, and offering programs and services for patients with kidney disease. However, the most important members of this dialysis care team are the patients themselves, their families, or caregivers.

Consultations

A single nephrology office consultation often fails to provide patients with an adequate understanding of chronic kidney disease. Enhanced care delivered by a predialysis interprofessional team leads to improved biochemical outcomes, a higher rate of planned dialysis initiation, fewer hospitalizations, and potential survival benefits. Despite these advantages, 36% of newly diagnosed ESRD patients in the United States in 2015 received no nephrology care before starting dialysis, resulting in more extended initial hospitalizations, increased complications, and higher mortality.

Early planning for dialysis access and, when feasible, preemptive renal transplantation offers the strongest opportunity for rehabilitation, since dialysis replaces only select filtration functions of the kidney and does not restore endocrine or anti-inflammatory activity. Consistent predialysis care correlates with improved clinical outcomes and reduced healthcare costs. Optimal management involves referral to an interprofessional team once declining GFR becomes apparent, ideally at least 12 months before dialysis. Dialysis timing can be estimated by extrapolating the eGFR trajectory to 10 mL/min/1.73 m².

Referral for interprofessional care occurs when eGFR reaches 15 mL/min/1.73 m², as comorbid conditions may precipitate abrupt renal decline requiring urgent dialysis. Group education sessions enable peer-to-peer learning, while support groups provide emotional reassurance for patients and families coping with ESRD. The care team typically includes a nurse educator, physical therapist, occupational therapist, dietitian, social worker, pharmacist, and, at times, a trained peer support volunteer. Effective collaboration and shared communication among team members guide individualized therapy. Use of an interprofessional dialysis access liaison has demonstrated improved fistula patency and reduced morbidity and mortality.[24][25][26][27]

Preparation

Vascular access is the essential first step in achieving effective hemodialysis. The gold standard is the distal AV fistula.[28] 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. For hospitalized ICU patients requiring hemodialysis, hemodialysis catheters may be placed in the internal jugular, femoral, or subclavian veins, with the right internal jugular vein preferred.

Preparation of appropriate infrastructure for home hemodialysis should be undertaken only after confirming the absence of any legal restrictions from the central or local government. All prerequisites should be met, and the home should be structurally sound, free from dampness, mold, and excessive environmental pollution, with reliable electricity and an adequate water supply. Appropriate provisions must be made for reverse osmosis water purification and for the disposal of wastewater, dialysate, and biomedical waste.

Community house hemodialysis offers a homelike, noninstitutional setting with flexible scheduling, similar to home hemodialysis. 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 (5 or more times a week), a dedicated machine and space in the community hemodialysis location are the best options. Those on a thrice-a-week or alternate-day regimen can share a machine. The home hemodialysis program is responsible for the infrastructure, equipment, and maintenance of the community house.[29]

Patients seeking nocturnal dialysis are limited to their bedrooms, while those fearing unintentional needle dislodgement may prefer daytime dialysis. Those with larger, more static hemodialysis machines have limited options for machine placement. At the same time, mobile batch dialysis equipment can be relocated, provided the necessary peripheral equipment and outlets are in place. The provision and undertaking of home dialysis involves sharing and dividing responsibilities between the home hemodialysis program and the patient. Both parties and clinicians must understand their responsibilities. An agreement should be documented as a patient contract or in the unit's policies and procedures. The liability towards installation and maintenance should be made clear at the beginning.

Technique or Treatment

Hemodialysis Techniques

As discussed above, the essential first step is establishing vascular access. Options for access include catheters, arteriovenous fistulas (AVFs), and arteriovenous grafts (AVGs).[30][31][32][33] 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 material is interposed between an artery and a vein due to inadequate vasculature.

Pediatric patients or patients with unstable blood pressure may require priming of the circuit with saline, albumin, or reconstituted whole blood. 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. Lower rates are used in neonates and pediatric patients, and critically ill patients who may not tolerate the rapid fluid removal and metabolic changes associated with IHD.

Negative hydrostatic pressure on the dialysate side is used to achieve adequate fluid removal (ultrafiltration). The chosen ultrafiltration rate for each session should achieve an optimal balance between euvolemia, solute clearance, and adequate blood pressure control, while minimising hemodynamic instability and intradialytic symptoms. Dialysate, or dialyzing fluid, is an electrolyte solution that approximates the electrolyte composition of extracellular fluid, with differences primarily in bicarbonate buffer and potassium concentrations. The solution's osmolality is close to that of plasma to prevent red blood cell hemolysis; the solution contains dextrose, sodium, potassium, magnesium, calcium, chloride, and bicarbonate. Dialysate may be generated online, prepared by mixing prepackaged salts, or supplied by the dialysis clinician.[34][35][36] 

Dialysis targets depend on the urea reduction ratio, that is, the fraction of blood urea nitrogen reduced per hemodialysis session, ideally 65% to 70%. Most patients receiving IHD require anticoagulation therapy to maintain an activated clotting time 1.5 to 2 times normal to prevent clotting within the dialysis circuit. Unfractionated heparin is the most common anticoagulant used; however, if a regional anticoagulation (anticoagulation of the circuit without systemic effect) is desired, dialysate containing citrate can be used.[37] The citrate binds to calcium at the dialyzer membrane, reducing clotting within the dialyzer. Hemodialysis dose should be individualized, taking into account the adequacy of ultrafiltration, control of hyperkalemia, hyperphosphatemia, and acidosis, as well as fluid removal.[38]

Continuous renal replacement therapy has become a popular method of renal support in pediatric patients and is commonly used in critically ill patients. Compared with IHD, evidence suggests that CRRT may improve the chances of renal recovery in critically ill patients surviving acute kidney injury.[39][40] CRRT uses both diffusion and convection: dialysate allows diffusion to remove small molecules, while convection clears both small and larger molecules via high ultrafiltration rates. High ultrafiltration may require volume and electrolyte replacement to compensate for the loss of these substances.

Although slower flow rates make CRRT less efficient than IHD, its continuous nature allows equivalent daily clearance with fewer metabolic shifts, and newer CRRT devices can achieve near-IHD flow rates for faster solute removal. Commonly used CRRT modalities are continuous venovenous hemofiltration (CVVH), which relies on high convective clearance and requires replacement fluids; continuous venovenous hemodialysis (CVVHD), which primarily uses dialysate for diffusion with minimal convection; and continuous venovenous hemodiafiltration (CVVHDF), which combines dialysate and replacement fluids for both diffusion and convection.

Anticoagulation and Hemofiltration Fluid 

Systemic heparinization can be used for anticoagulation; however, it may be associated with risks, eg, bleeding, heparin-induced thrombocytopenia, and the need for frequent monitoring to adjust the dose. Regional citrate anticoagulation acts by chelating calcium, a cofactor in the clotting cascade. Additionally, calcium is administered to the patient to prevent hypocalcemia. Citrate anticoagulation requires less frequent monitoring compared with heparin; however, disadvantages include the risk of acid–base disturbances, hypercalcemia or hypocalcemia, and citrate accumulation due to impaired metabolism or clearance. Anticoagulation should be used with caution in patients with underlying coagulation disorders.

Premade and fully compounded dialysate or hemofiltration fluid is usually used in CRRT. These fluids are available in a range of electrolyte concentrations to accommodate different clinical needs. Replacement fluids can be administered either before or after the hemofilter. Greater clearance can be achieved by increasing the dialysate or replacement fluid flow rate. A calcium gap, or citrate lock, occurs when excess citrate binds to free calcium in the patient, resulting in low ionized calcium despite normal or high total calcium levels.[41][42] Increasing clearance and reducing citrate delivery helps address this situation. 

Quality of Life Concerns

Dialysis patients have a reduced health-related quality of life (HRQoL) associated with increased morbidity and mortality, including: 

1. Physical factors: These impairments are characterized by limited or impaired mobility and role limitations, manifesting as sleep disorders (eg, obstructive sleep apnea), fatigue, and restless legs.
2. Mental factors: Mental health issues encompass depressive thinking and anxiety. Intensive hemodialysis has a positive impact on HRQoL by increasing the physical and psychological component scores and is also associated with significantly reduced postdialysis recovery time.[43]

Complications

Several complications are commonly associated with hemodialysis.

Intradialytic Hypotension

Intradialytic hypotension is defined as a decrease in systolic blood pressure of 20 mm Hg or greater, or a decrease in mean arterial blood pressure of 10 mm Hg, accompanied by associated clinical events.[44] 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 blood pressure lower than 90 mm Hg is associated with higher mortality.[45] Intradialytic hypotension may reflect severe underlying conditions, eg, infection, arrhythmias, myocardial ischemia, tamponade, hemorrhage, air embolism, or dialyzer reactions that require urgent recognition. 

This complication can result from rapid or excessive ultrafiltration, reduced plasma osmolality, autonomic dysfunction, diminished cardiac reserve, intake of antihypertensive medications, or dialysate-related factors, eg, temperature and electrolyte composition.[46][47][48] Intradialytic hypotension usually presents as dizziness, light-headedness, nausea, dyspnea, or subtle symptoms. Management includes reducing the ultrafiltration rate, maintaining the patient in the Trendelenburg position, and administering oxygen and a normal saline fluid bolus.

Intradialytic Hypertension

Volume overload, sympathetic overactivity, activation of the renin-angiotensin system, medications, and arteriosclerosis can contribute to intradialytic hypertension.[49][50][51] Intradialytic hypertension can be treated by using antihypertensive medications and achieving euvolemia. 

Muscle Cramps

The pathogenesis of muscle cramps in patients on dialysis is unknown. The origin of the cramps is considered neural and typically involves the lower extremity muscles; however, upper extremity muscles can also be involved. Electrolyte shifts (eg, hypokalemia and hypomagnesemia), changes in plasma osmolality, and plasma volume contraction can predispose individuals to cramps. Tissue hypoxia and other factors that trigger vasoconstriction and muscle hypoperfusion impair muscle relaxation. Treatment includes slowing the rate of ultrafiltration, increasing plasma osmolality with hypertonic saline, mannitol, or dextrose, using medications (eg, gabapentin or amitriptyline), massaging the affected extremity, and using warm compresses.[52][53] 

Dialysis Disequilibrium Syndrome

Dialysis disequilibrium syndrome is more common in patients during or soon after their first treatment. This complication is a clinical syndrome characterized by neurologic deterioration, restlessness, mental confusion, headache, occasional muscle twitching, and coma. It occurs due to a substantial gradient in urea concentration between CSF and blood, which causes water to move into the central nervous system, thereby raising intracranial pressure. Patients undergoing fast dialysis develop seizures and cerebral edema more often. A reasonable goal for urea concentration reduction is 40% over 2 hours, with a urea reduction ratio 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. Increasing the dialysate’s sodium concentration throughout treatment may be beneficial.[54][55]

Dialyzer Reactions

Anaphylactic type A reactions can present from mild-to-moderate symptoms, eg, itching, urticaria, coryza, watery eyes, abdominal cramping, fever, nausea, vomiting, and diarrhea to severe symptoms, eg, dyspnea, a feeling of impending doom, and hemodynamic instability. Symptoms may begin at any time during the first 30 minutes following dialysis.[56] The reaction can be due to hypersensitivity to ethylene oxide, used to sterilize dialyzers, or to bacterial peptide contamination. Anaphylactoid reactions are common in patients taking ACE inhibitors who undergo hemodialysis with AN-69 membranes, likely due to the enhanced generation of bradykinin from the membrane’s negatively charged surface, combined with ACE inhibition.[57][58][59] Surface-modified AN-69 membranes (AN-69 ST) or adjusting priming conditions can reduce bradykinin release and prevent these reactions, even in patients who continue to take ACE inhibitors.[60] Management includes termination of dialysis treatment, treatment with intravenous antihistamines, steroids, and epinephrine. Proper rinsing of dialyzers before use eliminates residual allergens and helps prevent them.

Type B reactions, which occur in patients dialyzed with new cellulosic membranes, are generally less severe than type A reactions and present with chest or back pain, dyspnea, nausea, vomiting, and hypotension. Symptoms usually appear within 15 to 30 minutes of starting dialysis and often improve as treatment continues. These reactions are mediated by complement activation and can be minimized by dialyzer reuse or by using more biocompatible membranes.[61][62]

Chest Pain and Dyspnea

Chest pain and dyspnea most often result from myocardial ischemia, volume shifts with rapid ultrafiltration, hypotension, or hypervolemia, but may also reflect severe conditions, eg, arrhythmias, hemolysis, air embolism, infection, or dialyzer reactions. Immediate management includes stopping ultrafiltration, reducing blood flow, positioning the patient in a supine position, administering oxygen, assessing vital signs, and evaluating for cardiac, hemolytic, or air embolic causes. Persistent symptoms, hypotension, hypoxemia, or suspected life-threatening etiologies require discontinuation of dialysis and urgent transfer to a hospital setting.

Hemolysis

Acute hemolysis during dialysis is a medical emergency characterized by port-wine appearance in the venous blood line, a marked fall in hematocrit, and a pink-colored plasma centrifuged blood sample. The patient should undergo hematologic investigations and be monitored for potential delayed hemolysis. A dialysate sample must be investigated to find the cause.

Air Embolism

Air embolism is a rare complication but can lead to hemodynamic collapse, cardiac arrest, and fatal consequences. Venous air embolism is often challenging to diagnose, and visualization of intracardiac air on transesophageal echocardiography is considered the most definitive diagnostic test.[63][64] Management includes placing the patient in the left lateral decubitus position with the head down or in the Trendelenburg position, administering 100% and hyperbaric oxygen, and withdrawing air from the cardiac chambers using a percutaneously inserted needle or a cardiac catheter.[65]

Fever

Patients undergoing hemodialysis are at increased risk for infection, and the development of fever during a hemodialysis session should prompt concern for a vascular access–related infection.

Other Complications

Other complications of hemodialysis include nausea and vomiting, headache, chest and back pain, and pruritus.[54][66][67][68] These symptoms may be related to an underlying disorder, hypotension, an early manifestation of disequilibrium syndrome, dyselectrolytemia, hypoglycemia, or psychological factors.[69][70] Acetaminophen and antiemetics administered during dialysis can help alleviate the symptoms.

In patients with recurrent and severe dialysis-associated headaches, reducing the duration of individual hemodialysis sessions to mitigate symptoms while increasing treatment frequency to preserve dialysis adequacy may be beneficial.[71] Switching to a different type of dialyzer membrane could reduce itching caused by low-grade hypersensitivity to blood circuit components.

Vascular Access Dysfunction

Vascular access dysfunction most commonly manifests as stenosis of arteriovenous access, which is the strongest determinant of the quality of life of a patient undergoing dialysis. This leads to reduced blood flow and an increased risk of thrombosis.[72] 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 reestablishes access.[73][74]

Electrolyte Imbalances

Electrolyte imbalances should be remediated by dialysis; however, they can also be precipitated by dialysis. Hyperkalemia is the most common and clinically significant complication in noncompliant patients, besides hypermagnesemia, hyponatremia, and hypocalcemia.[75] A cardiac arrest is twice as likely in patients undergoing hemodialysis as in those on peritoneal dialysis 3 months after dialysis initiation. Sudden cardiac deaths are most likely during the first 2 months after the initiation of hemodialysis. The predominant arrhythmias identified are ventricular fibrillation, pulseless electrical activity, and asystole. In the vascular access process, death may occur from cardiac arrhythmias, pulmonary edema, or contrast medium reaction.[72]

Vascular access precautions include avoiding additional trauma to the access arm, eg, wearing tight clothing or jewelry, carrying heavy objects, or sleeping on the affected limb. Blood draws and blood pressure measurements should not be performed on this arm. Needle insertion sites should be rotated to preserve access integrity, and gentle pressure should be applied after needle removal to achieve hemostasis. Patients should be instructed to contact a health care practitioner if bleeding persists or becomes profuse (>30 minutes). Bleeding, often related to heparin use during dialysis, can be effectively treated with protamine sulfate. Continuous monitoring of venous and arterial pressures is essential for detecting line disconnections. Needles should be securely taped, and safety measures such as wetness detectors and closed connector devices should be employed. Regular inspection of the access site for signs of infection (eg, redness, warmth, pain) is necessary. Loss of the normal bruit should prompt evaluation for access thrombosis to prevent limb ischemia.

Clinical Significance

CKD patients requiring dialysis accumulate uremic retention solutes, eg, asymmetric dimethylarginine (ADMA), indoxyl sulfate, and p-cresol, which may 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 chronic inflammation. Biomarkers, eg, 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, eg, carvedilol, in the prescription can improve outcomes.[76]

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 CKD increases the likelihood of CVD. Cardiovascular morbidity, mortality, and all-cause mortality are predicted by a fall in the eGFR and albuminuria. Albuminuria is a subtle indicator of kidney dysfunction, microvasculature health, and endothelial function. The early identification and management of cardiovascular risk factors in a patient with mildly reduced eGFR are imperative to ensuring that the patient does not die from CVD 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. Noncardiogenic 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 noncardiogenic 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 fibroblast growth factor 23 lead to atrial fibrillation, 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 hemodialysis 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 is seen more commonly in dialysis patients with comorbidities (eg, diabetes and preexisting atherosclerosis). The risk is directly proportional to the duration of dialysis. Patients undergoing dialysis also have a 3 times higher risk of stroke.

Enhancing Healthcare Team Outcomes

Dialysis serves as a life-sustaining therapy for patients with advanced kidney disease or end-stage renal disease, offering two primary modalities: hemodialysis and peritoneal dialysis. Hemodialysis can be delivered intermittently (IHD) or continuously (CRRT), with IHD providing rapid ultrafiltration for acute volume overload and CRRT offering continuous fluid and solute removal to maintain hemodynamic and metabolic stability in critically ill patients. Appropriate timing for initiating dialysis depends on clinical symptoms, volume status, and functional decline rather than kidney function alone. Early counseling regarding treatment options, including home or in-center hemodialysis, peritoneal dialysis, kidney transplantation, or conservative management, supports informed decision-making for patients and their caregivers. Mortality among dialysis patients is predominantly cardiovascular, highlighting the need for risk mitigation through pharmacologic strategies and careful monitoring.

Effective management of dialysis requires coordinated interprofessional collaboration. Physicians, general practitioners, and advanced practitioners assess disease progression, determine timing and modality selection, and monitor clinical and laboratory parameters. Nurses provide patient education, monitor hemodynamic stability, and facilitate adherence to treatment plans. Pharmacists optimize medication management, ensure safe dosing, and support cardiovascular protection. Dietitians guide nutritional interventions, and social workers support patients and assist with resource access. Consistent communication across the care team ensures timely recognition of complications, individualized therapy adjustments, and comprehensive patient-centered care, ultimately improving clinical outcomes, safety, and quality of life for patients requiring dialysis. 

Nursing, Allied Health, and Interprofessional Team Interventions

Home hemodialysis causes an additional burden for both caregivers and patients. 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 hemodialysis.

Sticking to a healthy diet has been shown to improve outcomes in patients undergoing hemodialysis.[77] A study has shown that periodic text messaging to advise dialysis patients on healthy eating habits has improved adherence to dietary recommendations and reduced the need for phosphate binder therapy. The reminders focus on guidance related to potassium, phosphorus, sodium, and fluid intake, as well as broader nutrition and lifestyle advice. These include encouraging the consumption of fresh, unprocessed foods to limit phosphate intake commonly found in packaged products; advising patients to read food labels carefully and select items containing less than 400 mg of sodium per 100 g; and recommending alternatives, eg, pasta, rice, and sweet potato, consumed 3 to 4 times per week, in place of regular potatoes to better control potassium intake.

Nursing, Allied Health, and Interprofessional Team Monitoring

Commencing home hemodialysis creates unique psychosocial issues affecting the patient and care partner. The home hemodialysis health care team must provide proactive interprofessional support, respite care, travel support, peer support, and financial support. Improper redressal of these aspects could cause patients to return to in-center hemodialysis. Some centers provide real-time monitoring of home hemodialysis treatments, and a panic button/alarm may be present to contact the local paramedic unit.[78]