Alternative techniques for end-stage renal failure

Alternative techniques for end-stage renal failureINTRODUCTION:

In France, the annual incidence of end-stage renal failure is 6 children / 1 million children under 15, ie 1.2 pediatric patients / 1 million inhabitants. Children under 5 represent 26% of patients.


They are in order of frequency renal hypoplasia-dysplasia associated or not with malformation uropathy (36%), glomerulopathies (26%) among which idiopathic corticoresistant nephrotic syndrome is the most frequent, hereditary nephropathies (17%) among Nephronophthisis is the most common (4.7%) and Hemolytic Uremic Syndrome (4.5%).The remaining 15% bring together exceptional causes and uncertain etiologies. About 2% of causes are unknown.

The preponderance of boys is related to a high prevalence of obstructive uropathies, particularly valves of the posterior urethra.


Replacement therapy is routinely initiated for glomerular filtration below 5 mL / min / 1.73 m2. In practice, the need for extrarenal treatment is judged on serum creatinine levels, greater than 600 μmol / L in a child under 20 kg or 800 μmol / L in a child over 20 kg, and blood urea level, greater than 35 mmol / L in a child under 20 kg and greater than 50 mmol / L in a child over 20 kg. Extrarenal treatment is sometimes started at a glomerular filtration level between 5 and 10 mL / min / 1.73 m2 when there are clinical signs of renal failure: asthenia, deterioration of the general state, increased anorexia or feeding difficulties in infants, and recent breakage of the growth curve of the uterus.

End-stage renal failure in the neonatal period poses different problems depending on whether or not there is a preserved diuresis. Supplements of water, bicarbonates and sodium chloride, adapted to urinary losses, alone can maintain an infant with glomerular filtration between 0.5 and 5 mL / min / 1.73 m2 for 7 to 9 months. only if you have a preserved diuresis, at least 20 mL / kg / day. A conservative diet given by the nasogastric route, or by gastrostomy, often leads to a satisfactory growth during this period, and makes it possible to reach a weight greater than 8 kg and a height of 70 cm for which extrarenal purification no longer poses complex problems. . The management of anuric infants is otherwise difficult, although it is theoretically and practically possible. It requires prior information from parents whose daily collaboration must be acquired to carry out such a therapeutic project.

All children treated as first-line by extra-renal treatment are on a waiting list for a kidney transplant with a cadaver kidney, or are engaged in a transplant procedure with a living donor. This attitude assumes that a contraindication to transplantation is also a contraindication to start extrarenal treatment. This is the case of only children with deep encephalopathy for whom the medical refusal of a substitute treatment must be carefully weighed and discussed.

Preventive renal transplantation before the extrarenal treatment stage, either by placing patients on the national list of coronary kidney transplantation, or by arranging early transplantation with a living donor, should always be considered in all renal diseases of which renal insufficiency is progressive (cystinosis, renal dysplasia associated or not with a malformative uropathy, hereditary nephropathy) and whose terminal phase is easy to predict with several months in advance. A glomerular filtration threshold between 10 and 15 mL / min / 1.73 m2, depending on the speed of progression, seems to be acceptable for the organization of a transplant. In the period 1981-1992, the pediatric EDTA registry reports 13% of preventive transplantation in children under 15 years of age. In the period 1990-1992, 42% of intrafamilial transplants and 20% of cadaveric transplants were in Europe.


There is no material or technical obstacle to performing a hemodialysis session in a wide range of weights ranging from 3 to 60 kg. The basic principles such as the use of osmosis water and concentrates with a bicarbonate buffer, a dialysate generator with ultrafiltration master, an extracorporeal circuit with an occlusive pump, and the security attached to these materials, are identical for all adult patients and children. A pediatric hemodialysis unit operates with the same facilities and equipment as a hemodialysis unit treating adult patients.

Technical adaptations concern extracorporeal tubing, dialyzers and session parameters.

Extracorporeal circuit volume:

The priming volume of the extracorporeal circuit must be adapted to the child’s volume, and must not exceed 10% of its value, ie 8 mL / kg.

The combination of neonatal tubing (31 mL) and smaller dialyzer surfaces (with a priming volume between 25 and 35 mL) provides a minimum priming volume of around 60 mL difficulty a hemodialysis session in a child of 7 kg. The range of pediatric tubing (priming around 100 mL) can be used with small surface dialyzers in children weighing 12 kg.Tubing for unipuncture is only needed for children whose arteriovenous fistula is exceptionally short and can be punctured with a single needle.

When the priming volume exceeds 8mL / kg, the simultaneous connection of the circuits 
arterial and venous, and restitution of the volume of saline contained in the 
extracorporeal circuit, often allow to maintain satisfactory hemodynamic stability. The initiation of the circuit with a blood-albumin mixture at 4% is an exceptional indication in children of very small weight (less than 3 kg).

Flow rate of the extracorporeal circuit:

A theoretical formula makes it possible to fix the flow of the circuit to: 2.5 × weight + 100. This formula should be considered only for the first sessions. The flow rate can then be gradually increased to 30 or 50% above this threshold without hemodynamic intolerance. Above 30 kg, the flow rate can often be maintained between 250 and 300 mL / min.

Choice of dialyzer:

It meets several criteria including the priming volume (see above), the surface and the type of membrane and its performance in terms of purification and ultrafiltration. Conventionally, the ratio between the surface of the patient and the dialyzer surface must be between 0.75 and 1, for a membrane with conventional performance (cellulose acetate type or low permeability polysulfone). This benchmark is very useful for the first sessions whose tolerance is sometimes difficult, but should not be a rigid rule for the entire period of hemodialysis. The optimization of the dialysis dose responds to the desire for optimal growth and weight, and a better comfort between hemodialysis sessions. The study of the nutritional status of children in hemodialysis conducted by the pediatric nephrology society showed that spontaneous caloric intake was proportional to the dialysis dose measured by Kt / V urea. The gain in calorie intake is statistically 40% when the Kt / V increases from 1 to 1.5. More recently, Abitbol et al showed that the treatment of small hemodialysis children with growth hormone was significantly more effective when the Kt / V urea exceeded 1.5.

The choice of the membrane meets the contradictory requirements of cost and quality of biocompatibility. A child without HLA (human leucocyte antigen) immunization, waiting for a first transplant, has a hemodialysis duration usually less than 6 months and can be treated with a cellulose acetate membrane. A hyperimmunized child, waiting for a second kidney transplant, or a non-transplantable child (often with graft failure secondary to relapse of nephrotic syndrome) should have the benefit of more expensive membranes but with better biocompatibility.

Choice of time and dialysis technique:

Twelve hours of hemodialysis per week divided into 3 sessions of 4 hours are a minimum threshold that it does not seem desirable to cross, when the residual renal function is less than 5 mL / min / 1.73 m2. This duration makes it possible to achieve the objective of a Kt / V equal to or greater than 1.5 with dialyzers of a conventional surface.Hemodiafiltration techniques that simultaneously combine the effects of a hemodialysis session and a hemofiltration session must, first and foremost, serve to optimize the dialysis dose more than to reduce its duration. The choice of the hours of the session will always have to take into account the school timetable.

Heparinization of the circuit:

Low molecular weight heparins have simplified the problem of anticoagulation of the extracorporeal circuit. A dose of 0.5 to 1 mg / kg of enoxaparin at the beginning of the session is sufficient for the prevention of coagulation accidents.Heparin-free dialysis is possible using high permeability polysulfone membranes, pediatric tubing without expansion vessels, extracorporeal circulation rate greater than or equal to 250 mL / min and five rinses per hour. It is only used in periods surrounding surgery.

Ultrafiltration rate and dry weight adjustment:

A flow rate greater than 15 mL / kg / h, corresponding to a weight loss of 5% relative to the dry weight, carries a risk of hypotension during the session. Excessive interdialytic weight gain may require prolongation of the session at 4 h 30 min or 5 h, or the use of variable profiles of ultrafiltration and sodium dialysate concentration. Dry weight adjustment is a constant concern in pediatrics. The child’s weight increases with growth, but can also rapidly decrease with infectious accidents or post-surgical periods. It is discussed according to the tolerance of the sessions, the level of the arterial pressure and the total protidemia dosed each week. In cases where the interpretation of these data seems insufficient to fix a weight, the measurement of the normal space (between 18 and 24%) is a reliable benchmark that can often control a difficult situation.

Vascular surroundings:

Vascular management in pediatric hemodialysis obeys the unique concern of preserving superficial arterial and venous capital to cover a lifetime. Arteriovenous fistula remains the most reliable vascular approach for long-term hemodialysis. Radial localization is possible even in children under 10 kg thanks to the use of the surgical microscope.since the use of this technique, the prevalence of distal fistulas is comparable in children under (78%) and over (88%) by 10 kg. The time of use and development is much longer than in adults and often exceeds 3 months. During this period, it is possible to resort to peritoneal dialysis, or to begin hemodialysis with an indwelling central catheter. The puncture of fistulas is done after local anesthesia by Emla® ointment which must be brushed on the skin 2 hours before the session. Fistula flow and echocardiography are carefully monitored to prevent the occurrence of secondary heart failure at an excess flow rate greater than 500mL / min / m2. Poorly tolerated hyperdebtness may require closure of one fistula and creation of another.

They are surgically placed in the right internal jugular vein, and their position is controlled under a luminance amplifier.Their use is very comfortable for children because of the painless and atraumatic nature of the connection. They do not induce cardiac hyperdebt, but the risk of complication, by thrombosis of the superior vena cava, prohibiting any new approach to the upper limbs is a limit to their generalization in pediatric hemodialysis.


The principles and automation of peritoneal dialysis are comparable in pediatrics and adult medicine. The peritoneal surface of the infant is 380 cm2 / kg against 175 in the adult. The volume of peritoneal dialysate should be between 30 and 50 mL / kg, and the clearance of creatinine should not be less than 50 L / week / 1.73 m2 (5 mL / min / 1.73 m2) to obtain a good purification. The automatic cyclers can dispense adjustable volumes with an accuracy of 5 mL, and are ideally suited for pediatric and neonatal use without modification. The usual duration of purification is 10 h / d, and can be done according to all modalities in use in adults: ambulatory cyclic peritoneal dialysis, recirculating chronic cyclic peritoneal dialysis or not, intermittent peritoneal dialysis. The peritoneal catheter has a length adapted to each range of weight and size.

It is also the easiest method to use in newborn oligoanuric and low weight infants for which management has been decided. The technique meets that of any peritoneal dialysis, but with a miniaturization pushed to the extreme. The main problems are the adaptation of flexible catheters, which must often be re-cut, and respiratory tolerance which often requires prolonged hospital supervision. Dialysate volumes are higher than in older children and can often reach 70 mL / kg / cycle. The use of cyclers is perfectly possible because of the accuracy of the volumes (5 mL) administered by machines of recent generations.

Chronic peritoneal dialysis has two advantages in pediatrics. It is a slow and gentle cleansing technique, which is particularly well tolerated and allows a broader water, sod and protein regime, due to its daily use and the loss of proteins in the effluent dialysate. The exchanges are done at home at night after a short learning period, and do not interfere with the school timetable. Its implementation and the organization necessary for the management of the equipment at home are greatly facilitated by home dialysis associations.


Control of dietary intake:

Children with end-stage renal disease systematically have a diet and close dietary surveillance. It aims to limit the intake of potassium and the protein-phosphate pair, and especially to regularly evaluate the caloric ingestas.

Good nutritional status is a prerequisite for good skeletal growth. It is even more difficult to obtain that these patients eat less than normal children, and the bioavailability of nutrients is less good. Spontaneously, a child in hemodialysis eats 65 to 80% of the recommended intakes in the normal child. This amount corresponds to 10 kcal / cm of height instead of 12 to 14. The optimization of these contributions depends on the dialysis dose and a dietary strategy to develop the appetite and the pleasure of eating. Supplementation in the form of daily gastric gavage by nasogastric tube or by gastrostomy is essential until the age of 2 or 3 years to obtain intakes of 100 to 120% of the recommended rates. It is sometimes useful beyond this age to recover a compromised nutritional situation. This technique of food substitution often allows a dramatic catch-up of weight and height. It requires a lot of skill, and tight supervision, to be instituted and supported at home by parents. The energy intake is half of carbohydrates and half of fat. The proportion of proteins does not exceed 7%. In practice, infant formula is supplemented with maltodextrins and oils rich in unsaturated fatty acids (sunflower).

When the child is older, a diet rich in fat and slow sugars is proposed.

Protein intake is calculated according to age. It is increased by protein losses in peritoneal dialysis. It is brought exclusively in milk form until the age of 1 year, at best by mother’s milk whose biological value is very high in humans and whose proteins are very little phosphorylated. Proteins are exclusively milk-based in infants. After dietary diversification, a system of parts (1 part = 4 g of animal protein) is used to guide the diet. Food of plant origin is readily replaced by deproteinated and demineralized products. The reduction in protein intake limits the intake of phosphates between 30 and 45 mg / kg / day in infants (400 to 800 mg / day in the big child).

Potassium intake is rigorously regulated according to an identical system of parts (1 part = 1 mmol). It involves the removal of dried vegetables, chocolate and all kinds of kernels (almonds, pistachios, peanuts, etc.), and soaking or deep-fried fresh vegetables.

The sodium intake is evaluated according to the residual natriuresis. Sodium restriction often involves the prohibition of salty foods (charcuterie, fermented cheese), but also bakery and pastry products that often contain abundant amounts of salt, except when made at home.

A weekly monitoring of the ionogram, of the calcemia and the phosphatemia, is done in hemodialysis to detect the variations of diet and treatments, and to assure a constant care, psychological and dietary

Use of erythropoietin and iron supplementation:

The use of erythropoietin in pediatric dialysis is comparable to that of adults. In our personal experience, an average hemoglobin of 11.5 g / dL requires a dose of erythropoietin of 60 to 260 U / kg / week (mean 170) and a 30% transferrin saturation factor.

Erythropoietin is administered intravenously in hemodialysis and subcutaneously in peritoneal dialysis.

In our hemodialysis unit, oral iron supplementation was completely discontinued in favor of intravenous supplementation during the session. A weekly infusion of iron, at a dose of 0.3 to 1 mg / kg / week, is sufficient to prevent iron deficiency during cruising. Biological index monitoring of iron metabolism is also essential for peritoneal dialysis despite low losses. Oral supplementation is required intermittently to compensate for losses from sampling.

Treatment of Skeletal Abnormalities: Calcium, Vitamin D and Growth Hormone

Calcium supplementation is given before meals at a rate of 100 to 300 mg / kg / day of calcium carbonate (ie 40 to 120 mg / kg / day calcium-element) for the purpose of adsorbing food phosphorus and optimize the absorbed amount of calcium. These doses are high, but respond to the need for bone mineralization until adolescence and control of hyperparathyroidism. Magnesium hydrocarbonate is also a useful way to adsorb dietary phosphorus in combination with calcium carbonate, but its poor digestive tolerance limits the increase in doses (50 mg / kg / d) and the excessive increase in magnesium calls for a reduction in the concentration of magnesium in the dialysate.

Of the hydroxylated derivatives of vitamin D, alfacalcidiol (Un-Alfa®) is the most widely used in pediatric dialysis. It is given 3 times / week, after each session of hemodialysis to limit bad compliance to this treatment. It is administered orally for the prevention of renal osteodystrophy (0.05 μg / kg, 3 times / week) and intravenously (up to 0.15 μg / kg, 3 times / week) to treat hyperparathyroidism when intact parathyroid hormone (PTH) levels exceed 500 pg / mL.Calcitriol in high doses (0.1 μg / kg, 2 times / week) orally has also been used successfully in this indication.Parathyroidectomy is sometimes necessary, especially in patients who have not received treatment during the chronic pre-term renal failure phase.

Prescription of recombinant growth hormone has not yet been approved for pediatric end-stage renal disease marketing authorization (AMM). Its effectiveness is poorer than during the conservative treatment phase. Current study protocols use doses ranging from 1 to 1.5 U / kg / week, often divided into subcutaneous injection 6 days / week. The main entry criteria are less than -1.5 DS (standard deviations) and a growth rate below average (no catch-up). Prior control of hyperparathyroidism, nutritional status and optimization of the dialysis dose are essential.

Paramedical Entourage:

Sessions are provided by pediatric nurses with strong training in hemodialysis techniques. They must know how to control the approach of the children at the time of the most aggressive gestures such as the puncture of the arteriovenous fistulas. During the session, educators from the school of the hospital take care of the children’s recreation or school education. The older ones will benefit from private lessons in mathematics, French or languages, by often volunteer teachers. A psychologist and a social worker have a specific role of moral support for families, father, mother, brothers and sisters who often live with difficulty these constraints. They also contribute to the organization of the life of the group of children in treatment: common outings and holidays. The dietician is also a key figure in the hemodialysis unit.


Pediatric peculiarities of transplant preparation Children awaiting transplantation have left-sided nephrectomy for hypertension and nephro-ureterectomy for repeated episodes of acute pyelonephritis. Right nephrectomy is done on the day of transplantation to complete the gesture.

The morphological study (cystography with permissive images) and functional (bladder urodynamics) of the lower urinary tract is indispensable in boys with posterior urethral valves, even if resection in the neonatal period has been fully satisfactory. This assessment is also necessary in the rare neurological bladders that reach the stage of end-stage renal failure. Enlargement enterocystoplasty must be done before the bladder has lost sufficient compliance.

A definitive cutaneous derivation through an intestinal graft is sometimes necessary when the bladder abnormalities are associated with vesicosphincteric synergy disorders.

Particularities of the surgical act:

The only surgical problem that distinguishes the child from the adult is that of the disproportion between adult and small kidney recipients. In this case, the vessels are implanted on the aorta and inferior vena cava near the bifurcations.

Live donor transplantation only concerns 10 to 20% of children according to French centers. The donor is one of the two parents, in the majority of cases, and a brother or sister major in the other cases.

Risk of thrombosis and its prevention:

Early failures in young recipients are attributable to excess vascular thrombosis secondary to the use of kidneys from donors under 2 years of age, accounting for nearly half of the causes of failure. It is currently better to refuse kidneys from children under 6 months of age. Prevention of the risk of thrombosis by low molecular weight heparin during the first 3-4 weeks of transplantation, in case of donor or recipient under 5 years limits the frequency of these failures. The best results are nevertheless obtained with adult kidneys in this age group.

Features of immunosuppression:

The medical management of a kidney transplant is identical in children and adults. Immunosuppression must take into account the problem of growth, and implies a parsimonious use of glucocorticoids. Discontinuous administration should be systematically recommended after 9 months of transplantation in the absence of rejection, possibly after histological control of the graft.


We must distinguish two situations in terms of survival of the graft: the transplant with a cadaveric donor (about 80 to 90% of the cases according to the French centers) and the transplantation from a living donor (10 and 20% of the cases according to the French centers). Carcass grafts have a survival (European average of EDTA 1983-1986) of 82% at 2 years and 74% at 3 years for children who have received ciclosporin. Long-term survivals only concern patients not treated with ciclosporin, and are around 50% at 10 years of age and slightly below 40% at 15 years of age. The survival of living donor kidneys is slightly better at 77% at age 5 and 73% at age 8 in the Necker-Enfants Malades series. Potter, in a series beginning in 1964, reports similar numbers in the first 5 years, 60% survival at 10 years, 52% at 15 years and 35% at 20 years.

The survival of transplanted children is excellent: 90% at 5 years, 80% at 15 years for transplants with a corpse kidney.It is 97% at 8 years old with a living donor kidney. Infections account for half of the causes of death in large pediatric series, while tumor and cardiovascular mortality is virtually zero.

Causal diseases sometimes recur on the graft. The most difficult problem is the recurrence of an idiopathic nephrotic syndrome in 30% of cases, with a loss of the graft in nearly half of the patients. The recurrence of a hemolytic uremic syndrome is exceptional, and only concerns chronic forms. Cystinosis is a metabolic disease secondary to lysosomal deficiency that is not present in the transplanted kidney and does not recur. On the other hand, extrarenal, ocular, thyroid, pancreatic and neurological complications continue their progression, and legitimize the continuation of the treatment based on cysteamine salts despite the discomfort (permanent odor of foul-smelling sulphurous vapors) and the constraints (administration every 6 hours) that it involves.

The growth of children with end-stage renal disease is discussed in another chapter. Renal transplantation remains an important means of optimizing the growth of the stature, at least in children whose renal function is close to normal (glomerular filtration greater than 60 mL / min / 1.73 m2) and whose corticosteroid treatment has been sufficient lowered or changed.

Rehabilitation is one of the most important outcomes of pediatric kidney transplantation. A school activity can be resumed 2 months after the transplant, and often with a normal rhythm after 6 months of transplantation. Socio-professional rehabilitation is very satisfactory. In a study of patients who had been transplanted for more than 10 years, Gagnadoux et al had 40% of adults with normal full-time work integration and almost 25% of adolescents who were studying. These results are the result of ongoing work by the social team that constantly surrounds families.

The management of children with end-stage renal disease may seem like a therapeutic challenge against duration. It requires a complete and complex organization, in which the specialization of a small number of pediatric services has been successful. The treatment constraints remain very heavy, but the results in terms of survival and quality of life of many patients are at the height of these investments.