Hemodialysis International 2014; 18:573–582
Hemodialysis for infants, children, and adolescents Amrit KAUR,1 Andrew DAVENPORT2 1
Birmingham Childrens’ Hospital, Birmingham, UK; 2UCL Centre for Nephrology, Royal Free Hospital, London, UK
Abstract Children with chronic kidney disease stage 5 requiring dialysis can be treated by peritoneal or hemodialysis. In the United Kingdom nearly twice as many children receive peritoneal dialysis compared with hemodialysis. Technical aspects of pediatric hemodialysis are challenging and include the relative size of extracorporeal circuit and child’s blood volume, assessment of adequacy,technical and complications of vascular access. Alternatives to standard hospital-based hemodialysis are also increasingly available. Optimizing nutritional status with the support of specialist pediatric dietitians is key to the management of children receiving hemodialysis. The effects of chronic illness on growth and school achievement, as well as the psychological, emotional, and social development of the child should not be underestimated. This review focuses on the above elements and highlights common pediatric practice in the United Kingdom. Key words: Children, hemodialysis, adolescents, infants
INTRODUCTION Hemodialysis was first described in children in the 1960s,1 and peritoneal dialysis approximately a decade later.2 More children with chronic kidney disease stage 5 requiring dialysis (CKD5d) are now treated by peritoneal dialysis in the United Kingdom, with nearly twice as many receiving peritoneal dialysis compared with hemodialysis,3 although worldwide, more children are treated by hemodialysis.4 Hemodialysis can be challenging in
Correspondence to: A. Davenport, MD, UCL Centre for Nephrology, Royal Free Hospital, University College London Medical School, Rowland Hill Street, London NW3 2PF, UK. E-mail: [email protected]
Funding: Birmingham Children’s Hospital, Royal Free Hospital. Neither author has any conflict of interest.
children because of technical difficulties such as extracorporeal circuit volume and maintaining vascular access. In addition, hemodialysis is associated with a marked disruption to schooling and family life. Regardless of renal replacement modality, the developmental, nutritional and social needs of the child must be addressed. In the United Kingdom, the decision to initiate renal replacement therapy (RRT) in children is usually considered when the estimated glomerular filtration rate (GFR) is less than 15 mL/min/1.73 m2 or the child has signs or symptoms of uremia, volume overload, or growth failure despite appropriate medical therapy. Current UK clinical guidelines advise that RRT should be initiated before estimated GFR falls below 6 mL/min/1.73 m2.5 Peritoneal dialysis (PD) is often the preferred choice in children in the United Kingdom provided there are no medical contraindications to this technique. Hemodialysis is usually selected for those children where PD has failed, the child has had previous intra-abdominal surgery
© 2014 International Society for Hemodialysis DOI:10.1111/hdi.12163
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disrupting the peritoneal cavity or social circumstances contraindicate dialysis offered in the home environment. Pediatric hemodialysis in the United Kingdom is centralized and provided in specialized regional pediatric centers offering a multidisciplinary approach supporting both the child and family. The multidisciplinary team comprises specialist staff including pediatric nephrologists, urologists, radiologists, anesthetists, specialist nursing staff, dietitian, pharmacist, play therapists, teachers, and psychologist. Treatment goals include not only providing dialysis, but also achieving normal growth, psychosocial development, and minimizing interference to education and family life.
PEDIATRIC HEMODIALYSIS The extracorporeal circuit and hemodialyzer There are some fundamental differences between adult and pediatric hemodialysis practice. For example, in pediatric practice, blood lines and the hemodialyzer are selected on the basis that children can tolerate 8% (absolute maximum 10%) of their total blood volume in the extracorporeal circuit,5 based on total blood volume estimated as 80 mL/kg for infants and 70 mL/kg for older children. If the smallest available hemodialysis circuit exceeds this critical volume, it can be primed with 4.5% human albumin solution or donor blood to prevent symptomatic hypovolemia.6 However, repeated blood transfusions increase the risk of possible sensitization for future renal transplants, and wherever possible, blood should be from the same donor to minimize third party sensitization. As the blood lines are of smaller caliber, blood pump speeds tend to be somewhat faster, aiming for 8–10 mL/ kg/minute, compared with 3–5 mL/kg/minute for adult hemodialysis.7 The blood pump head rollers have to be adjusted for the size of the dialysis lines, otherwise mechanical hemolysis may occur if an adult blood line is used in a dialysis machine set up for pediatric lines. Historically, small children, and those with acute kidney injury were reported to be more prone to the dialysis disequilibrium syndrome,8 and to reduce the rate of fall in plasma osmolality, the dialyzer surface area should be chosen to be smaller than or equivalent to the body surface area (BSA) of the child. The smallest dialyzer available has a surface area of 0.25 m2. Dialyzers vary in terms of both flux (β2 microglobulin clearance) and hydraulic permeability (water permeability), and so can vary from low flux and low hydraulic permeability through to high flux high permeability. Membranes with
increased hydraulic permeability risk volume depletion and their use requires accurate volume control by the hemodialysis machine. Several options are now available for monitoring changes in plasma volume during dialysis, with different manufacturers monitoring changes in hematocrit, blood viscosity and oxygen saturation, utilizing sound, or light cell technology.9,10
Fluid removal and dialysate biochemistry Fluid loss required is calculated by the inter-dialytic weight gain. To help avoid hypovolemia and hypotension, UK clinical guidelines recommend that the maximum volume of fluid removed during any single session should not exceed 5% of the child’s ideal weight.5 Proportionally, more children have residual renal function than in adult practice, and as such, volume removal is typically less, particularly for those children with salt and water losing kidney disease such as renal dysplasia or obstructive uropathy. Although most children receiving dialysis do not have overt cardiac disease, children are at risk of myocardial stunning during hemodialysis.6,11 Whether reversible changes in left ventricular contractility are primarily consequent upon relative intravascular volume depletion remain to be determined.11 Determination of the ideal weight remains clinically based. Although there have been studies suggesting a possible role for bioimpedance and biomarkers such as natriuretic peptides in adult practice in determining ideal weight,12 these have not been evaluated in pediatric practice, as normal reference ranges have not been established. Monitoring changes in relative blood volume may potentially be helpful,13 as no change in hematocrit or blood viscosity with ultrafiltration is suggestive of persistent volume overload, whereas rapid increases are suggestive that the child is approaching or has reached ideal weight, and unable to compensate for volume loss.14,15 The choice of dialysate is individualized for each child, and although bicarbonate is the standard buffer concentrations used by centers varies between 32 and 35 mmol/L. However, it should be remembered that most dialysates also contain 2–3 mmol/L of acetate to prevent calcium deposition within the dialysis machine, and as such, although metabolic acidosis needs to be corrected for optimal growth, supra-physiological alkalosis should equally be avoided to prevent electrolyte shifts (hypokalemia and calcium loading) and respiratory center effects. Due to the widespread use of calcium-based oral phosphate binders, lower dialysate calcium concentrations are typically used (1.25 mmol/L). Most centers use dialysates containing physiological concentrations of glucose (1 g/L or 5.5 mmol/L) to prevent hypoglycemia.
Hemodialysis International 2014; 18:573–582
Potassium-free solutions are rarely used due to the risk of hypokalemia, with most children dialyzing against 1.0– 3.5 mmol/L. As pediatric practice includes children with salt losing states, dialysate sodium concentrations typically range from 138 to 144 mmol/L. Higher dialysate sodium concentrations on one hand risk increased thirst and inter-dialytic weight gains, but on the other hand, there is a reduced risk of intra-dialytic hypotension. However, the potential advantages of individualizing the dialysate for any child have to be balanced against storing a variety of dialysate electrolyte solutions and manufacturing errors in dialysate composition, machine proportioning and nursing programing errors. As such, many centers opt for standardization of dialysate composition to reduce costs and programing errors. Advances in technology have produced dialysis machines with software to monitor relative blood volume and fuzzy logic programs designed to adjust the dialysate sodium concentration and ultrafiltration according to changes in the relative blood volume to help reduce intradialytic hypotension.7,10 During dialysis, blood flow to the skin is reduced and core temperature increases, which may lead to vasodilatation and hypotension. As such, cooled dialysate reduces the risk of intra-dialytic hypotension and cardiac stunning but children may complain of the cold. Some dialysis machines can be programed to cool the dialysate to prevent any increase in body temperature, and reduce the risk of hypotension. If the child is hypoalbuminemic and nephrotic, priming the dialysis circuit with 20% human albumin solutions may allow adequate fluid removal while maintaining vas-
cular stability and minimizing the risk of intra-dialytic hypotension, but can risk precipitating pulmonary edema.
Hemodialysis adequacy As transplantation is the preferred renal replacement modality for children with CKD5d and in the United Kingdom children have a preferential weighting on the transplant waiting list, most children in the United Kingdom do not wait long for a transplant so do not experience a long hemodialysis career and do not experience dialysis amyloid or other consequences of long-term dialysis observed in adults. The concept of adequacy has therefore been extrapolated from adult studies based on small solute clearance.16 Urea clearance is commonly assessed using Kt/V or urea reduction ratio. Measurements of adequacy are not clearly defined in children, which probably reflect that urea removal per se is not linked to growth and development. Current UK recommendations for laboratory and clinical indices have been summarized in Table 1.5 Children are typically dialyzed at least three times per week, with each session lasting up to 4 hours.17 Again, this is tailored to the individual, depending on inter-dialytic weight gain, biochemical disturbances, and in the very young, the need to create volume to allow for optimization of enteral feeding. A maximum of six sessions per week may be necessary in order to achieve optimal growth in very young children. A minority of children may have developed chronic kidney disease due to a metabolic error of metabolism with the accumulation of a toxic compound, for example, oxalate, methyl malonic acid,
Table 1 Laboratory and clinical indices of adequate hemodialysis5 Indices Predialysis serum bicarbonate Predialysis serum potassium Predialysis serum phosphate Serum calcium adjusted for serum albumin Serum albumin corrected for calcium × phosphate product Parathyroid hormone Serum aluminum Hemoglobin Ferritin Establish dry weight Pubertal stage Blood pressure Urea reduction rate (URR) Single-pool sessional Kt/Vurea
Hemodialysis International 2014; 18:573–582
Recommendation 20–26 mmol/L 3.5–6.5 mmol/L Within and preferably nearer to the 50th centile for the age-appropriate normal range Within the age-appropriate normal range Less than 4.8 mmol2/L2 Less than twice the upper limit of normal No greater than 60 micrograms/L Greater than the lower limit of the age-appropriate normal range 100–800 micrograms/L Assess 2–4 weekly depending on age of child Assess every 3 months in those older than 10 years Within the age-appropriate normal range More than 65%, aim for 70% Greater than 1.2
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and ammonia. In these cases, both more frequent and longer dialysis sessions may be required to achieve adequate reduction in serum concentrations to reduce other organ damage from these toxic compounds.18
Complications during hemodialysis Hypotension predominantly occurs due to movement of water out of the intravascular compartment quicker than the refilling rate from the extracellular and intracellular compartments. The risk of intra-dialytic hypotension depends upon a variety of factors, including a rapid decrease in serum osmolality, vasodilation in response to warm dialysate, and high ultrafiltration rate to correct excessive inter-dialytic salt and water ingestion.6 Hemolysis, air embolism, and anaphylactic reactions can also rarely occur. As blood passes across the dialyzer, bradykinin and the anaphylotoxins C3a and C5a are generated and these may cause hypotension. This reaction depends upon pH and the negative electrical charge of the dialyzer surface, and so can be exacerbated by using stored blood to prime the circuit, dialyzers with high negative surface charges, large heparin boluses and prescription of angiotensin converting enzyme inhibitors that delay bradykinin breakdown.19 Although rare, dialysis disequilibrium syndrome due to too rapid a reduction in plasma urea concentration, with a slower urea movement from tissues into the plasma, leads to the development of an osmotic gradient between plasma water and the cells, resulting in a movement of water from the plasma water into tissues, includingthe brain, which can result in cerebral edema with confusion, seizures, and coma.8 The risk of disequilibrium can be reduced by using intravenous mannitol for the first dialysis session in patients with a high plasma urea, dialyzing using a smaller surface area dialyzer and slower blood and dialysate flows.20 Most centers opt for targeting a 30% reduction in blood urea when initiating dialysis to reduce the risk of dialysis disequilibrium.
As − log (Ct C0) approximates to Kt V where Co and Ct are the pre- and postdialysis blood urea concentrations, respectively, natural logarithm, K is the manufacturer’s urea clearance at a specified blood and dialysate flow, V is volume of distribution of water in the child and t the session time. Then, taking an example of a 50-kg child, using a dialyzer with a K of 200 mL/min (0.2 L.min) with a blood pump speed of 250 mL/min (using