The editors and current author would like to thank and acknowledge the significant contribution of the previous author of this chapter from the 2004 first edition, Dr. James H.E. Ireland and Dr. Julie Won Ireland. This current third edition chapter is a revision and update of the original author’s work.

A 16 year old girl with a past medical history of systemic lupus erythematosus (SLE) presents with intractable nausea and vomiting, and increasing edema for two days. She was diagnosed with SLE at age 14. A biopsy of her kidney at that time revealed a diffuse proliferative glomerulonephritis with prominent crescents and minimal fibrosis. Her creatinine at that time was 1.5, and she was started on cyclophosphamide, prednisone and furosemide.

Exam: VS: T 36.5 C, P 110, RR 18, BP 180/110, weight 75 kilograms. She is very nauseated and actively vomiting. She responds to verbal commands and is slightly somnolent, but oriented. She has pale conjunctiva and no oral lesions or thrush. Her lungs are clear. She is tachycardic and has a rub. Her abdomen is soft and nontender and her lower extremities have significant edema.

Her CBC demonstrates a low hemoglobin of 7.5 g/dl with an MCV of 92. Her chemistries show elevated potassium at 5.7 mEq/L, low bicarbonate at 13 mEq/L, markedly elevated BUN at 119 mg/dL and creatinine of 5.9 mg/dL. A renal ultrasound shows small echogenic kidneys with no hydronephrosis, masses or stones. A chest x-ray shows an enlarged cardiac silhouette and enlarged pulmonary vessels (fluid overload). An echocardiogram reveals a moderate pericardial effusion, no tamponade, enlarged filling chambers, and normal contractility. Emergent vascular access is obtained, and she is started on daily hemodialysis (HD). Within a week her symptoms resolve so she is transitioned to outpatient hemodialysis three days a week on Monday, Wednesdays and Fridays, each session is scheduled for 4 hours duration.

This case illustrates the use of acute hemodialysis (HD) for a patient with uremia secondary to chronic kidney disease caused by SLE. Indications that require acute dialysis include severe metabolic acidosis, hyperkalemia (serum potassium greater than 6.5 mEq/L), uremia, volume overload refractory to diuretics, and overdose of dialyzable drugs (1). The indications to initiate dialysis in chronic kidney disease patients are not as well defined and require the expertise of a nephrologist. Generally, children who have an estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73m² should be monitored closely. If they develop any signs of uremia (e.g., nausea and vomiting, altered mental status, seizures, pericarditis, or bleeding diathesis), fluid or blood pressure instability, rapid decline of eGFR, inadequate nutrition/growth, or signs and symptoms that are refractory to medical treatment (e.g., anemia, acidosis), then dialysis should be initiated (2).

Hemodialysis (HD) is one form of renal replacement therapy. HD requires vascular access such as a percutaneous double lumen catheter (known as a Vas Cath) that can be placed in a large vein, usually the internal jugular or femoral vein, but sometimes the subclavian vein (2). This vascular catheter has large lumens to permit optimal venous blood flow to facilitate venovenous (as opposed to arteriovenous) hemodialysis. As with any central venous line, there is a risk of bleeding (exacerbated by uremia), stenosis (especially with the use of the smaller subclavian vein), thrombosis, and infection. The longer the line is kept in place, the greater the risk of infection. Infection is a drawback to using this type of vascular access; however, the ability to immediately initiate acute or emergent HD is ideal.

If chronic, maintenance HD is needed (as with chronic kidney disease), more permanent vascular access should be established. One method, and the preferred option, involves connecting a vein to an artery to create an arteriovenous fistula (AVF) (2). This is usually done in the non-dominant arm in case ischemia or other complications occur. Once it is decided that permanent vascular access is needed, the patient and nurses should ensure that the designated limb is not used for blood draws, intravenous lines, or arterial punctures to minimize any potential trauma to the blood vessels prior to fistula surgery. The two most common locations to create an AVF are the wrist radiocephalic and the elbow brachiocephalic. After surgery, the fistula requires 2 to 3 months to mature and cannot be used during this time (3). Maturation is the histologic process of venous thickening and dilating, essentially taking on some of the characteristics of the attached artery. These changes enable the venous portion of the graft to accept the repeated insertion of the HD needle. If the patient is already requiring HD, a Vas Cath can be used until the fistula is mature and usable. After surgery, the fistula should have an audible bruit and palpable thrill, which should be checked at least daily to confirm patency and blood flow.

If an arteriovenous fistula is not anatomically possible, another type of permanent access is an arteriovenous graft (AVG) (2). This involves the use of a synthetic tube to connect the artery and the vein (3). Common sites for synthetic grafts include the radial artery to the basilic vein, the brachial artery to the basilic vein, and the brachial artery to the axillary vein. Maturity is faster than the fistula, usually occurring in 2 to 3 weeks. Unfortunately, an AVG is more likely to clot and occlude than an AVF (4). If this should occur, medical therapy (thrombolysis) or a surgical procedure can be done to salvage the graft (interventional procedures or thrombectomy).

Once vascular access is established via Vas Cath, AVF, or AVG then hemodialysis can be performed. During HD, blood leaves the body via tubing into the HD unit. It passes along a semipermeable membrane with a dialysis solution (dialysate) flowing along the other side of the membrane. Solute particles from the blood then pass down their concentration gradient into the dialysate for removal. The mechanism of dialysis can be simplified based on standard diffusion: where particles (solutes) of high concentration (in the blood) move down their concentration gradient to an area of low concentration (the dialysate). The movement is across a semipermeable membrane, so larger particles will cross more slowly or not at all. Thus, the smallest particles will be removed the fastest. Also, the steeper the concentration gradient, the quicker the removal. Blood and dialysate run through a filter in opposite directions, with the membrane separating them. This countercurrent flow maximizes the concentration gradients for solute removal. The blood is then returned to the body (3). Other aspects of the HD prescription include the type of membrane, flow rate of blood and dialysate, temperature, length of time on dialysis, and composition of the dialysate (3). Modern machines can monitor these functions and monitor for potential air emboli and blood leaks in the dialyzer as well.

The dialysate is purified water with precise amounts of various ions and glucose. For example, a typical solution contains: sodium 140 mEq/L, potassium 3.0 mEq/L, calcium 2.0 mEq/L, magnesium 0.75 mmol/L, bicarbonate 25 mEq/L, and glucose 100 mg/L. Different ionic concentrations can be used for different clinical situations. For example, a patient with a normal potassium of 4.0 mEq/L can use a dialysate with 4.0 mEq/L potassium since his potassium concentration does not need to be changed or corrected. A hyperkalemic patient with a serum potassium of 5.0 mEq/L should use a dialysate with a lower concentration of potassium (e.g., 2.0 mEq/L) so that dialysis can reduce and normalize the patient’s serum potassium. A patient with a potassium greater than 7.0 mEq/L may even require a dialysate with no potassium for the first hour of dialysis.

Besides normalizing ionic concentrations, acid-base status, and removing metabolic waste products, another function of dialysis is to remove accumulated water. Water moves across the membrane under hydrostatic forces (this is known as ultrafiltration) (3). The degree of that force determines the amount of net water movement. Small particles within the water are also removed during this process, which is called convection. Particles larger than the dialysis membrane pore size will be left behind in the blood (3).

There are a number of complications with HD including nausea, vomiting, cramping, disequilibrium syndrome, hypothermia, hemolysis, reactions to dialyzer that could even result in anaphylaxis, bleeding, thrombosis, stenosis, fever, infection, and hypotension. Disequilibrium syndrome is a dangerous complication that can occur during or after HD. It is usually due to the rapid removal of urea (a significant osmotic agent) causing a fluid shift into the brain cells, which could even result in cerebral edema. In mild cases, it can be associated with headaches, nausea, and vomiting, but more severe manifestations include seizures (more common in children than adults) and coma. Preventative measures include limiting the blood flow rate and the total time on HD for the first few sessions to prevent large fluxes (3). Hypothermia during dialysis occurs because the temperature of blood drops when traveling through dialysis tubing and machinery. This can be prevented by heating units in the dialysis machine (5). HD patients have an increased risk for infection because of frequent access to their bloodstream. If an HD patient has a fever, then blood cultures should be obtained. The most common pathogens include Staphylococcus species, gram-negative enterobacteriaceae, and enterococcus species (3). Empiric therapy should be directed at these organisms and may require vancomycin coverage for methicillin-resistant Staphylococcus aureus (MRSA). Species of Candida can also infect these sites.

Hypotension is a common complication during HD and may require volume replacement. If a HD patient continues to experience hypotension during dialysis but fluid removal is necessary, then more frequent HD sessions with a smaller volume of fluid removal per session may be required (5). Additionally, some patients tolerate fluid removal better if dialysate sodium concentrations are increased, this is known as sodium modeling. If large changes in fluid status are avoided, hypotension during the session is minimized (3). When patients needing HD are critically ill, unable to tolerate such a drop in blood pressure, or are already on vasopressor support (for example, in septic shock), another form of HD called continuous renal replacement therapy (CRRT) may be used. This form of dialysis is done continuously (compared to three times a week for 4 to 5 hours in standard HD). It is often the preferred modality for the management of patients who are hemodynamically unstable (5).

Peritoneal dialysis (PD) is another form of dialysis and is the most common method of dialysis for pediatric patients. In this method, an indwelling catheter is placed in the abdomen, usually under general anesthesia, and the PD solution (another form of dialysate) is circulated through the peritoneal cavity. In PD, the peritoneum acts as a biological dialysis membrane, and solutes (metabolic waste products, blood urea nitrogen, and potassium) cross this from the blood to the dialysate (2). The dialysate effluent (that now includes the metabolic waste products and excess potassium) is then drained from the abdomen. The PD solution can be changed manually every few hours or changed through an automated cycling machine (so that PD can be performed during sleep). The time from PD dialysate infusion to drainage is known as the dwell time. PD can also be used in the acute setting, but it is not as efficient in correcting hyperkalemia, hyperphosphatemia, or hyperammonemia as HD, so if these values are critical then HD or CRRT should be considered. The advantages of PD include: vascular access is not needed, complicated machinery is not required, large volume fluid shifts do not occur, and this can be performed at home after parental and patient training (5).

A major complication of PD is peritonitis, commonly presenting as acute clouding of the dialysate effluent. Additional signs and symptoms include fever, chills, abdominal pain, vomiting, abdominal distention, and changes in ultrafiltrate (amount of fluid removed). Coagulase-negative staphylococci, S. aureus, gram-negative organisms (including, E. coli, Klebsiella species, and Pseudomonas aeruginosa), and S. viridans are often positive in dialysate cultures in the setting of PD-associated peritonitis (6). An additional drawback of peritoneal dialysis is the presence of an external catheter from the abdomen, which may make children self-conscious.

There are a few other terms that arise in discussions of dialysis. Continuous venovenous hemofiltration (CVVH) refers to venovenous hemodialysis which focuses on convection as the dominant dialysis mechanism, while continuous venovenous hemodiafiltration (CVVHDF) utilizes both diffusion and convection. These differences are beyond the scope of this chapter.

In summary, all forms of dialysis can be a lifesaving therapy for acute or chronic kidney disease, certain overdoses, metabolic acidosis, and electrolyte disturbances. While dialysis can substitute for native kidneys in patients with end-stage renal disease, children on dialysis do not thrive as well as they would with a functioning renal transplant, therefore dialysis should act as a bridge until renal function returns, or the patient is able to receive a kidney transplant.

Questions
1. What are the indications for acute hemodialysis in pediatric patients?
2. In what situation is CRRT preferred over hemodialysis?
3. What are the advantages of peritoneal dialysis?
4. What are three complications that may occur in patients undergoing hemodialysis?
5. How would a peritoneal dialysis patient present with peritonitis?

References
1. Gallo PM. Nephrology. In: Kleinman K, McDaniel L, Molloy M (eds). Harriet Lane Handbook, 22nd edition. 2021. Elsevier, Philadelphia. pp. 472-501.
2. Kliegman RM, St. Geme JW, Blum NJ, et al. Chapter 550. Renal Failure. In: Kliegman RM, St. Geme JR, Blum NJ, et al. (eds). Nelson Textbook of Pediatrics, 21st edition. 2019. Elsevier, Philadelphia. pp. 2769-2779.
3. Rees L. Hemodialysis in Children. In: Avner ED, Harmon WE, Niaudet P, Yoshikawa N, Ema F, Goldstein SL. (eds). Pediatric Nephrology, 7th edition. 2016. Springer. pp: 2398-2422.
4. Shroff R, Calder F, Bakkaloglu S, et al. Vascular access in children requiring maintenance haemodialysis: a consensus document by the European Society for Paediatric Nephrology Dialysis Working Group. Nephrology Dialysis Transplantation. 2019;34(10):1746-1765. doi:10.1093/ndt/gfz011
5. Frishberg Y, Rinat C, Cohen RB. Renal Replacement Therapy (Dialysis and Transplantation) in Pediatric End-Stage Kidney Disease. In: Yu ASL, Chertow GM, Luyckx VA, Marsden PA, Shorecki K, Taal MW (eds). Brenner and Rector’s The Kidney, 11th edition. 2020. Elsevier, Philadelphia. pp. 2406-2444.
6. Verrina E, Schmitt CP. Peritoneal Dialysis in Children. In: Avner ED, Harmon WE, Niaudet P, Yoshikawa N, Ema F, Goldstein SL. (eds). Pediatric Nephrology, 7th edition. 2016. Springer. pp: 2339-2397.

Answers to questions
1. Severe metabolic acidosis, hyperkalemia, uremia, treatment-resistant volume overload, and overdose of dialyzable drugs.
2. In hemodynamically unstable patients.
3. PD can be done at home without complex machinery or vascular access, and no significant fluid shifts in the patient.
4. Hypotension, hypothermia, disequilibrium syndrome, hemolysis, reactions to dialyzer, bleeding, thrombosis, stenosis, and infection.
5. Clouding of dialysate effluent, abdominal pain and/or distention, vomiting, fever, chills, and/or decreased ultrafiltration.