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| REVIEW ARTICLE |
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| Year : 2022 | Volume
: 5
| Issue : 2 | Page : 56-63 |
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Optimizing the hemodialysis prescription and assessment of dialysis adequacy in children
V Hamsa1, Nivedita Kamath2
1 Division of Pediatrics, M. S. Ramaiah Medical College Hospital, Bengaluru, Karnataka, India
2 Department of Pediatric Nephrology, St. John's Medical College, Bengaluru, Karnataka, India
| Date of Submission | 30-Mar-2022 |
| Date of Decision | 14-May-2022 |
| Date of Acceptance | 06-Jul-2022 |
| Date of Web Publication | 31-Dec-2022 |
Correspondence Address:
Nivedita Kamath
Department of Pediatric Nephrology, St. John's Medical College Hospital, Sarjapura Road, Koramangala, Bengaluru - 560 034, Karnataka
India
 Source of Support: None, Conflict of Interest: None
Hemodialysis (HD) is an important modality of kidney replacement therapy in children with kidney failure. Vascular access in children can be challenging. Although central venous catheters are commonly used, arteriovenous fistulae provide an effective and sustainable access for HD. To provide optimal HD, the prescription should be tailored to each child. The size of the dialyzer and tubings and the extracorporeal circuit volume must be adapted to the size and weight of the child. Dialysate composition and duration of dialysis are altered to suit the metabolic profile, and the ultrafiltration volume is decided based on the hemodynamic status and interdialytic weight gain. To ensure that optimal dialysis is provided, parameters of dialysis adequacy are measured at regular intervals. Although clearance of urea (Kt/V) is the recommended measure of dialysis adequacy, it is important to assess growth, nutrition, blood pressure control, metabolic profile, and quality of life as measures of adequate dialysis in children.
Keywords: Adequacy, children, hemodialysis, prescription, vascular access
How to cite this article:
Hamsa V, Kamath N. Optimizing the hemodialysis prescription and assessment of dialysis adequacy in children. Asian J Pediatr Nephrol 2022;5:56-63 |
| Introduction | |  |
Hemodialysis (HD) is an important modality of kidney replacement therapy (KRT) in children. Technical issues such as high extracorporeal circuit volume, maintaining vascular access, impact of the dialysis on school attendance, disruption of family life, and high caregiver burden make HD in children challenging.[1],[2],[3],[4],[5],[6]
| Indications for Chronic Hemodialysis in Children | | |
Most experts recommend initiating maintenance dialysis once the glomerular filtration rate (GFR) is below 8-12 ml/1.73 m2/min.[7] Dialysis should be initiated at higher GFR if the child has clinical features suggestive of uremia, evidence of protein-energy wasting, refractory metabolic abnormalities (hyperkalemia, metabolic acidosis, and hyperphosphatemia) and/or volume overload with medical therapy alone. In children, decreased school performance and restricted daily activities are also important factors to be considered.[8]
| Vascular Access | | |
Vascular access is an important aspect in the care of children and adolescents with end-stage kidney failure (KF). Long-term vascular access in children has unique considerations, due to the low body weight and small caliber veins.
Central venous catheters
The International Paediatric Haemodialysis Network (IPHN) Registry data showed that, the initial long-term dialysis access was central venous catheters (CVC) in 73% children with KF, arteriovenous fistula (AVF) in 26%, and arteriovenous graft (AVG) in 1% of children.[9] CVCs are useful in situations requiring emergency dialysis and avoid pain due to recurrent cannulation.[10] Tunneled catheters are preferred due to lower rates of infections and longer survival periods compared to nontunneled catheters. Nontunneled CVCs should be used as a temporary access until an arteriovenous fistula is created or other modalities of KRT such as peritoneal dialysis or renal transplantation are performed. The 2019 Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines recommend that preferential placement of CVC should occur sequentially in the right internal and external jugular veins due to direct anatomy followed by left internal and external jugular veins and femoral veins. Subclavian veins are best avoided due to high rate of central venous stenosis.[11]
CVCs are placed percutaneously, under ultrasound guidance using Seldinger technique, with the catheter tip just outside the right atrium in case of a single tip and with one tip of the catheter inside the right atrium, while the other outside the atrium, about 1 cm proximal to the first in case of a staggered tip catheter, for optimal dialysis.[12] The choice of CVC based on the weight of the child is given in [Table 1].[2] | Table 1: Size of central venous catheters based on the weight of the child
Click here to view |
Although CVC is the most common vascular access used, it predisposes patients to a range of complications. During catheter insertion, arterial puncture, pneumothorax, emboli, and hematomas have been reported.[12] After CVC insertion, the risks of infection, catheter malfunction secondary to thrombus or fibrin formation, and venous stenosis are common.[13]
The European Society for Paediatric Nephrology Dialysis Working Group suggests using CVC in patients who are anticipating a kidney transplant within a short time, in very small children, and in the child who presents in the need of urgent HD or when awaiting peritoneal dialysis and maturation of AVF.[14]
Arteriovenous fistula
AVF is the preferred mode of vascular access in children.[11] AVF is superior to CVC as AVF has higher rates of patency, longer survival, need fewer interventions, associated with lower rates of infection, better adequacy and lower morbidity and mortality.[15],[16],[17],[18],[19],[20],[21] In 2006, KDOQI adopted the “Fistula First” initiative, which recommended creation of AV fistulas, advising at least 68% usage in prevalent patients on HD.[7] Planning, creating, and surveillance of the access require a multidisciplinary team including dialysis nurses, pediatric nephrologists, vascular surgeons, and interventional radiologists.[15]
All children with KF and their caretakers should be educated about vein preservation, irrespective of their initial choice of KRT modality. The forearm cephalic, antecubital, and upper arm veins should be preserved by avoiding venipuncture above the wrist in both the arms.[14] Distal-to-proximal approach and using superficial veins for AVF creation help in preserving vessels for future vascular access sites.[11] The following points have to be taken into consideration while planning AVF - age and size of the child, anticipated need of duration of HD, history of prior access, hand dominance, patient/family preferences, surgical /centre expertise for AVF creation.[21],[22] AVF can be successfully created and managed in children older than 10 years and/or weighing >20 kg.[16] However, microsurgical techniques have been used to create AVFs in children <10 kg. Prospective studies in pediatric population as well as IPHN registry have reported an average maturation time of 8–10 weeks with no difference in maturation time between radiocephalic and brachiocephalic AVFs.[1],[9],[16],[23] Prior to first needling, ensure that the vein is >6 mm diameter, fistula is lesser than 6 mm from skin surface, blood flow is >600 ml/min, and at least a segment of 6 cm is available for needling (Rule of 6) using Duplex ultrasonography. Once mature, AVF is cannulated using 17G needle, either using rope ladder or buttonhole technique under aseptic precautions. Surveillance of AVF includes routine clinical examination and duplex ultrasound, once in 3–6 months. Vascular surgery referral should be sought in case AVF is not functioning or if complications such as aneurysms, pseudoaneurysms, infection, thrombosis, bleeding, infiltration (hematoma), stenosis, and steal syndrome are noted.
The advantages and disadvantages of CVC and AVF are compared in [Table 2]. | Table 2: The advantages and disadvantages of central venous catheters and arteriovenous fistulae in children
Click here to view |
Arteriovenous graft
AVG is a modified form of AVF, wherein a prosthetic segment (usually polytetrafluoroethylene) is used to connect an artery and vein. The advantage of AVG over AVF is its short maturation time (days); however, infections and stenosis rates are higher.[4]
Extracorporeal circuit
The extracorporeal circuit comprises the needle/catheter volume, blood tubings, and dialyzer volume. A child can safely tolerate <10% of the total blood volume in the extracorporeal circuit.[3] Priming with 5% human albumin solution or packed red blood cells is used if the circuit volume exceeds the limit, to prevent symptomatic hypovolemia.[5] The pediatric blood lines are of smaller caliber, and the volume ranges from 56 to 112 ml.
| Dialyzer | | |
The dialyzer membrane surface area should be less or equivalent to the child's body surface area.[3] Dialyzers vary in terms of both flux and hydraulic permeability. The ultrafiltration coefficient (KUf) is the permeability of a membrane to water per unit of transmembrane pressure. Dialyzers with KUfs of <10 mL/h/mm Hg are low flux and 15–60 mL/hr/mm Hg are termed high flux. High-flux dialyzers, used in hemodiafiltration (HDF), provide better permeability for middle and larger molecules. The mass transfer area coefficient (KoA) is the product of the permeability coefficient of the dialyzer membrane for a particular solute (Ko) and total effective membrane surface area of the dialyzer (A). Dialyzers with KoAurea values <500 ml/min are low-efficiency dialyzers, 500–800 ml/min are moderate-efficiency dialyzers, and >800 are high-efficiency dialyzers.[24]
| Blood Flow Rate | | |
Blood flow rate (BFR) is a significant determinant of the solute clearance. Higher BFRs increase solute clearance but can compromise cardiovascular stability, whereas the lower BFRs are associated with clotting of the extracorporeal circuit. In children, BFRs are set at 5 mL/kg/min (range, 3–8 ml/kg/min).[25]
| Dialysate Flow Rate | | |
The optimum dialysate flow rate (DFR) is 1.5–2.0 times the BFR. Many modern-day machines can reduce the DFR to 100–300 ml/min.
| Dialysate Composition | | |
The dialysate composition should be individualized for each child. Bicarbonate is the standard buffer concentration used currently, with bicarbonate values between 32 and 35 mmol/L. Most dialysate solutions also contain 2–3 mmol/L of acetate to prevent calcium deposition. The plasma bicarbonate concentrations between 20 and 23 mmol/l are the postdialysis target. Metabolic alkalosis should be avoided to prevent hypokalemia, hypercalcemia, and respiratory center depression. Lower dialysate calcium concentrations (1.25 mmol/L) are preferred due to widespread use of calcium-based phosphate binders. To prevent hypoglycemia, dialysate contains physiological concentrations of glucose (1 g/L or 5.5 mmol/L). The dialysate potassium concentration is usually set at 2 mmol/L, though dialysate preparations with potassium content ranging from 0 to 3.5 mmol/L are available. Low potassium concentrations (0–2 mmol/L) are not used routinely as the predispose to cardiac arrhythmias. Dialysate sodium concentrations typically range from 138 to 144 mmol/L. Hyponatremic dialysate will lead to dialysis disequilibrium and hypotension, whereas hypernatremic dialysate leads to increased thirst and increased interdialytic weight gain. Dialysate temperature is maintained at 35°C–37°C. Warm dialysate solution results in vasodilatation and peripheral pooling of blood, increasing the risk of intradialytic hypotension. Cooling the dialysate to 0.5°C lesser than the patient's tympanic membrane temperature is associated with lesser incidence of intradialytic hypotension and better postdialysis recovery time.[3],[5],[25]
| Ultrafiltration Rate | | |
The maximum volume of fluid removed during any single session should not exceed 5% of the child's ideal weight, to avoid hypotension. Although the amount of fluid removal per hour that a child will be able to tolerate is quite variable, a generally safe starting point is <10 mL/kg/hr. Children with pulmonary edema or severe fluid overload may require removal of larger fluid volumes. Children tend to have more residual renal function compared to adults, owing to their native kidney disease (renal dysplasia or obstructive uropathy); hence, volume removal should be individualized based on child's urine output and interdialytic weight gain.[5],[6],[25]
| Anticoagulation | | |
Anticoagulation of the extracorporeal circuit should be determined by evaluating the risk of bleeding versus clotting the circuit. Standard regimens consist of a bolus dose of 15–20 units/kg of unfractionated heparin (UFH) at the start of dialysis, followed by a continuous infusion of 10–20 units/kg/h, stopping the heparin infusion over the last 30 min of dialysis. Low-molecular-weight heparin can also be used as an alternative to UFH. They have a longer half-life and require a single dose. Newer anticoagulants such as serine protease inhibitors (nafamostat), proteoglycans (danaparoid), and direct thrombin inhibitors (argatroban) are in the pipeline for children on maintenance dialysis.[26] Heparin-free dialysis using intermittent saline flushes should be performed in children with high risk of bleeding.
| Length of Dialysis Session | | |
The first dialysis in a patient with chronic kidney disease should be restricted to 60–90 min to keep the urea reduction ratio to <40%, to avoid dialysis disequilibrium syndrome. The length of the first dialysis session is based on the need for ultrafiltration in case of fluid overload/pulmonary edema. The duration of dialysis is then sequentially increased to 4 hr per session. During the first few sessions of the dialysis to prevent rapid reduction in blood urea, BFR is kept to the minimum. Hyperosmotic agent (mannitol, 50% dextrose) may be given at the end of the session to prevent rapid shifts in serum osmolarity.
A case vignette with a model HD prescription is described in [Table 3].
| Hemodialysis Adequacy | | |
The concept of dialysis adequacy has evolved over time. From being synonymous with the clearance of small solutes such as urea and creatinine, dialysis adequacy has now evolved into multidimensional entity of dialysis and nondialysis-related parameters. The goal of providing adequate dialysis is to ensure patient well-being in addition to achieving solute and fluid removal.[27]
| The Evolution of Small-Solute Clearance as a Measure of Adequacy | | |
Kt/Vurea became the standard measure of dialysis adequacy since the landmark paper was published by Gotch and Sargent in 1985.
The initial Kt/Vurea was derived from urea kinetic modeling. The single-pool spKt/Vurea assumes that urea is distributed in a single compartment, i.e., the extracellular compartment and is in equilibrium with the intracellular compartment. Kt/Vurea is used as a measure of the clearance of urea during dialysis, where K (ml/min) is the clearance of urea (ml of plasma cleared of urea per unit time), t is the time on dialysis in minutes, and V is the volume of total body water where urea is distributed, making Kt/Vurea a dimensionless entity.
Dialyzed blood gets mixed with the undialyzed blood as the dialysis proceeds and concentration gradient between the blood and dialysate compartment reduces in a logarithmic manner. During the duration of dialysis, urea also gets generated (G) in the body and is added to the urea pool. During dialysis, urea is not only removed by diffusion but also by ultrafiltration, and the ultrafiltration volume changes the total body water volume. Taking all these aspects into consideration, the equation was modified as follows:
spKt/V = −ln (C1/C0 − 0.008t) + (4 − 3.5C1/C0) × UF/W
C1 – Postdialysis blood urea nitrogen (BUN) concentration; C0 – predialysis BUN concentration; t – time on dialysis, UF – volume of ultrafiltration (l); W – postdialysis weight (kg). The C1/C0 is denoted as “R” or the ratio of postdialysis to predialysis urea.
The single-pool model overestimates urea clearance as it does not take into account the urea inbound and rebound. Dialysis rapidly removes urea from the extracellular space, but due to slow equilibration, urea gets sequestered in the intracellular space. After dialysis, the equilibration of urea from the intracellular to extracellular space continues to happen over the next 30–60 min, resulting in urea rebound. The equilibrated Kt/V considers the urea inbound and rebound effects and is a more accurate estimate of the urea clearance.[27]
The predialysis sample for urea is drawn before using saline or heparin. The postdialysis urea sample is obtained by a slow blood flow method (reducing the blood flow to about 100 ml/min for 10–20 s at the end of the dialysis session) or a stop dialysate flow (stopping dialysate flow for about 3 min) method. In children, the slow blood flow may not be possible due to low BFRs; hence, the stop dialysate flow method is preferred.
Urea reduction ratio (URR)
SUN - serum urea nitrogen
Urea reduction ratio, a simplified measure of urea removal through dialysis, does not account for either urea generation or the influence of ultrafiltration volume on urea removal.[3] The URR is recommended to be maintained at >65%.[26] URR is also defined as 1-R; hence, URR is taken into account in the spKt/V calculation.
Initial observational studies in large cohorts showed that lower Kt/Vurea was associated with higher mortality. The HEMO study found no difference in mortality in the higher Kt/Vurea group when compared to the standard dose group.
Subsequent studies from DOPPS showed that Kt/Vurea <1.2 was associated with higher mortality. Based on these studies, the KDOQI guidelines (2015) recommended a minimum single-pool Kt/Vurea (spKt/Vurea) >1.2 per session of HD, with a target spKt/Vurea of 1.4.[7],[28]
| Challenges of Urea Kinetic Modeling in Children | | |
Extrapolating the dialysis adequacy formulae from adults to children is fraught with problems. There is little evidence in the pediatric population to correlate the Kt/Vurea threshold to meaningful clinical outcomes.
The target Kt/V for children has not been studied widely. Children have a higher total body volume and require lesser dialysis to achieve the same Kt/Vurea. Formulae for calculating total body water overestimate the water volume in healthy children.[29] The metabolic activity and protein intake are higher in children and the urea generation is likely to be different. The states of malnutrition, obesity, fluid overload, change in body size, and composition with growth make it difficult to extrapolate formula and calculations from the adult population.[30]
| Real-Time Measurement Of Adequacy | | |
Ultraviolet spectrophotometry studies the decaying absorbance of the dialysate for small solutes such as urea, creatinine, and uric acid and concurs well with eKt/V.[27]
Ionic dialysance transiently increases the dialysate sodium to measure the drop in conductivity across the dialyzer membrane. Sodium clearance is used as a surrogate for urea clearance. Ionic dialysance has shown to correlate well with standard measures of small-solute clearance.[27]
| Dialysis Parameters Beyond Small-Solute Clearance that Influence Adequacy | | |
With advances in dialysis, it is now being understood that dialysis adequacy is more than just small-solute clearance.[31]
The frequency and duration of dialysis and type of dialyzers have a significant influence on dialysis adequacy. Clearance of potassium and phosphate has been shown to be important surrogates for clinical outcomes in adults on dialysis. The HEMO study and the MPO study did not find any significant improvement in mortality or cardiovascular outcomes with better middle molecule clearance achieved by high-flux dialyzers in comparison with low-flux dialyzers. However, in patients with a longer dialysis vintage and lower serum albumin, middle molecule clearance was associated with better survival.[31] Ultrafiltration rate and volume have an important bearing on outcomes. Ultrafiltration helps remove urea and middle molecules by convection. The HDF, Heart and Height (3H) study showed a better clearance of B2 microglobulin and inflammatory markers with HDF in comparison to HD in children. HDF was associated with a reduction in the progression of vascular disease and better patient-related outcomes.[32]
Dialysis time is being considered an important aspect for achieving adequate dialysis and is independent of Kt/Vurea. Although large trials like the FHN trial did not show a significant difference in hard outcomes like mortality with increased weekly dialysis time, there was a significant improvement in surrogate outcomes like left ventricular hypertrophy.[29]
| Advances in Dialysis | | |
Frequent HD has shown to be associated with lower incidence of intradialytic hypotension, better blood pressure control, phosphate removal, and better quality of life.[33] HDF was associated with better blood pressure control, lower inflammation, and better bone disease control in children.[34]
With the trend and benefits of more frequent dialysis being demonstrated by several studies, the KDOQI guidelines were modified to recommend a target weekly standard Kt/Vurea (stdKt/Vurea) of 2.3 with a minimum recommended Kt/V of 2.1.[7]
| Looking Beyond the Dialysis Prescription for Measures of Adequacy | | |
Vascular access
A functional access is necessary for providing optimal dialysis. Despite several complications associated with CVCs which compromise the quality of dialysis, they continue to be the most common vascular access used in children across the world. The “Fistula First” initiative should be applied to children on HD to provide an adequate vascular access for dialysis.[30]
Fluid management and hypertension
High interdialytic weight gain causes hypertension and left ventricular hypertrophy. Reduced capillary density, compromised subendocardial perfusion, myocardial dysfunction, and arrhythmias have been documented. High interdialytic weight gain results in high ultrafiltration rates and is associated with myocardial stunning.[35] In adults, interdialytic weight gain >4 kg, high rate of ultrafiltration (>13 ml/kg/hr), and failure to achieve target weights are associated with poor outcomes.[7] In children, interdialytic weight gain >4% has been associated with left ventricular hypertrophy.[36]
Patient education to restrict salt and fluid intake is important to reduce interdialytic weight gain. Regular re-assessment and modification of dry weight must be done. Ambulatory blood pressure is an important tool to uncover masked hypertension.
Control of metabolic and mineral bone disease parameters
Adequate clearance of small solutes such as potassium and phosphate are markers of adequate dialysis. Hyperkalemia is associated with cardiac arrhythmias and sudden cardiac death. High phosphate levels are associated with hyperparathyroidism, increased carotid intimal medial thickness, and abnormal pulse wave velocity.[7],[37]
Dietary restriction of phosphate and phosphate binders, preferably calcium-based binders, is recommended in children on dialysis. Increased time on dialysis has shown to improve phosphate clearance.[7]
Nutrition and growth
In children on dialysis, protein energy wasting (PEW) is common and a U-shaped association between serum albumin and hospitalization frequency was noted.[38] Low height SDS is associated with mortality and BMI has U shaped association with mortality.[39] Inadequate clearance during dialysis contributes to chronic inflammation, an important risk factor for PEW.[40] Adequate dialysis in addition to optimizing nutrition is necessary to prevent PEW.
Preservation of residual kidney function
The residual kidney function (RKF) removes uremic toxins such as protein-bound solutes that are not removed by dialysis. Better fluid balance, potassium removal, phosphate clearance, lower erythropoietin requirement, better quality of life, and lower mortality have been documented in patients with good RKF.[41]
Preservation of RKF function can be done by preventing intradialytic hypotension and minimizing the use of nephrotoxic medications. Biocompatible dialyzers and better water quality result in lower inflammation.[41]
Health-related quality of life
Children on RRT have a high hospitalization rate and readmissions within thirty days of discharge, with cardiovascular events being the most common cause of hospitalization.[42],[43]
Health-related quality of life in children on dialysis is significantly worse when compared to healthy population.[44] In adolescents on HD, quality of life was lowest in the domains of leisure activity, energy–vitality, relationships with friends, and physical well-being.[45] Sleep disorders were prevalent in more than three quarters of patients on dialysis, and restless leg syndrome was the most common sleep disorder. The impact of sleep disorder on quality of life was noted.[46]
The SONG-KIDS initiative identified survival, physical activity, fatigue, lifestyle restrictions, and growth as important outcomes for patients. They also identified kidney function, survival, infection, anemia, and growth as important outcomes for caregivers. This emphasizes the need for looking beyond the biochemical measures alone for adequacy and focusing on patient and caregivers perceptions.[47]
| Conclusions | | |
The dialysis prescription should be tailored to the individual patient's clinical and laboratory profile. Kt/Vurea is the most common measure of dialysis adequacy and a minimum Kt/Vurea of >1.2 is recommended. There is increasing emphasis on the need for a multidimensional measure of dialysis adequacy, which takes into consideration all key aspects of dialysis and the patient outcomes.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]
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