Only since the end of the 1980s have infants with endstage

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1 Proceedings of the ISPD 2006 The 11th Congress of the ISPD /07 $ August 25 29, 2006, Hong Kong Copyright 2007 International Society for Peritoneal Dialysis Peritoneal Dialysis International, Vol. 27 (2007), Supplement 2 Printed in Canada. All rights reserved. LONG-TERM PERITONEAL DIALYSIS IN INFANTS Lesley Rees Great Ormond Street Hospital for Children, London, United Kingdom Although the numbers of infants requiring dialysis are small, management of these patients presents many challenges. Mortality is high in infants with comorbidities, complications of dialysis are common, and most of these infants need enteral feeding. However, the long-term outcome for otherwise healthy infants is comparable to that for older children. Perit Dial Int 2007; 27(S2):S180 S184 Correspondence to: L. Rees, Great Ormond Street Hospital for Children, NHS Trust, Great Ormond Street, London WC1N 3JH U.K. Reesl@gosh.nhs.uk S180 KEY WORDS: Infant; ethics; mortality; growth; nutrition; development. Only since the end of the 1980s have infants with endstage renal failure (ESRF) been accepted for renal replacement therapy (RRT). Before that, the technical difficulties of managing such small children and the ethical dilemmas associated with their uncertain outcome meant that many nephrologists believed treatment to be unjustified. Indeed, as recently as 1998, only 50% of pediatric nephrologists responding to an international survey stated that they would offer dialysis to patients under 1 year of age, and fewer again (40%) would offer this treatment to those less than 1 month old (1). However, as long-term data began to emerge showing satisfactory outcomes for growth, development, and subsequent transplantation (2,3), attitudes changed (4), and today, most countries with available resources offer treatment to most infants. Still, debate remains about whether RRT should be offered to all infants regardless of associated comorbidity, a factor that significantly affects the success of treatment (2,5,6). EPIDEMIOLOGY The numbers of infants needing dialysis are small although in centers with a high incidence of congenital nephrotic syndrome, they may represent one third of the pediatric ESRF population (7). In the United Kingdom, numbers varied between 15 and 27 in any year during , an annual incidence of 3 per 1 million population (8). These figures are comparable to those in the United States, where 6 new patients per 1 million population of the same age start dialysis each year (9). The real incidence of severe renal-tract abnormalities is not known because no details have been published of the numbers of related spontaneous abortions and pregnancy terminations or of the numbers of infants with severe comorbid conditions who are not referred for RRT. However, it does seem that parents are increasingly expecting all available treatments to be offered to their infants. In a study of 20 infants starting peritoneal dialysis (PD), more than half of the families had been offered termination of pregnancy and all had refused, including two families who subsequently went on to refuse RRT (3). DIAGNOSES Diagnoses are predominantly structural abnormalities of the urinary tract such as dysplasia with or without reflux or obstruction (60% 80%). Congenital nephrotic syndrome is the next most common diagnosis, and cortical necrosis is the third. Thereafter, small numbers of infants are diagnosed with autosomal recessive polycystic kidney disease and renal venous thromboses, and then come even smaller numbers of diagnoses of conditions more commonly seen in older children (2,8). Over the last few years, the percentage of infants whose renal abnormality is diagnosed antenatally has risen to more than 50%, but earlier discovery has had little impact on either the incidence or spread of diagnoses, which have both remained stable (8). ISSUES SPECIFIC TO THE MANAGEMENT OF INFANTS WITH ESRF In addition to all the problems that affect older children, other specific issues arise concerning infants who require RRT:

2 PDI JUNE 2007 VOL. 27, SUPPL 2 PROCEEDINGS OF THE 11TH CONGRESS OF THE ISPD Is RRT justified? Which RRT modality should be chosen? How are nutrition and growth to be managed? Justification for RRT: Whether to initiate RRT is one of the most difficult questions facing pediatric nephrologists (10), and the ethics surrounding withdrawing or withholding treatment have been eloquently discussed (6,9). That decision is a particular issue for infants with other co-existing congenital abnormalities, who represent about one third of the infant renal failure population. In 20 infants on PD at our center, 14% had developmental delay; 7%, congenital heart disease; 3%, gut problems; 2%, hypothyroidism; 2%, respiratory problems; and 2%, blindness and deafness. There were also individual cases of CHARGE and VATER association, Wilms tumor, and other syndromes (Down, Jeune, Alagille) (2). Such abnormalities contribute to morbidity and mortality in their own right, and these infants are the ones who do particularly badly on RRT. Some families may decide that they do not wish to inflict further pain and suffering on their infant, and they choose conservative management rather than RRT. In the United Kingdom, about 3 families choose this option each year (8). Arriving at such a decision requires careful counseling (6). In addition to comorbidity, factors that are important in influencing decision-making include pulmonary hypoplasia and oliguria, which also limit survival (2,8,11 14). On the other hand, many infants, particularly those with congenital structural abnormalities, are polyuric, and so the ongoing electrolyte and water losses mean that such infants may survive many months even if untreated but at considerable cost to their growth and development. Furthermore, some improvement in renal function may occur over the first year of life, as in normal infants, and so outcome may be difficult to predict. Indeed, some are able to come off dialysis as many as 4% in a U.K. series (8). Parental bonding with an infant can lead to reversal of a decision for conservative management, by which time irreversible damage to growth and development may have occurred. Some families opt for intensive management of their infant, with dialysis and early transplantation. However, even in a child with no comorbidity, the input required from the family and multidisciplinary team (emotional, time-related, and financial) cannot be overestimated. Nonetheless, strict attention to nutrition, the dialysis program, and medications can result in a successful outcome for the infant with ESRF. It has to be remembered that, because of the very rapid growth in children of this age, only very frequent contact with the family can ensure adequate dialysis and nutrition. For example, the expected weekly weight gain during the first 6 months of life is 200 g that is, over a week, an infant weighing 3.8 kg should increase in weight to 4.0 kg. Based on a daily feed volume of 150 ml/kg, the daily feed should increase from 570 ml to 600 ml. Estimates suggest that 6 contacts per month by a dietitian are necessary per patient in children under 5 years of age, and so even more contacts are likely to be required in infants (15). Furthermore, if the dialysate fill volume is 40 ml/kg, then over the course of the week, that volume should increase from 152 ml to 160 ml. It can therefore be seen that, without frequent medical, nursing, and dietetic attention, the infant on PD will rapidly become underdialyzed and underfed. Most infants will go home dialyzed by cycling machines overnight and with feeds that are administered both during the day and overnight by feed pump. These factors, together with medication administration and the need to be able to assess the importance of small changes in weight and blood pressure, present a huge burden for the family. Although some infants managed with such intensity may start dialysis and run a course that is relatively straightforward until transplantation, escaping complications entirely is rare. Choice of RRT Modality: The purpose of RRT is to optimize growth to allow early transplantation, which has been shown to be successful even in patients under 2 years of age (16). However, ensuring that vaccinations are complete is important, and so transplantation before 15 months of age is unusual. In the United Kingdom, overnight cycling PD is selected in more than 80% of infants (8). This choice stems from the difficulty of obtaining vascular access for hemodialysis (HD) in small blood vessels and from the need to prime HD lines with blood, which confers a risk of HLA sensitization. Problems in maintaining vascular access are also very common. We found a revision ratio of 40% in 18 infants on long-term HD. Furthermore, although growth rates are maintained, the catch-up seen on PD is not evident (17). Access complications are less common in PD, although at our center, 35 catheters were placed in 20 infants over a mean of 17.3 months, and 24 episodes of peritonitis occurred in the 20 infants, 10 of whom required catheter replacement once, and 2 of whom required replacement twice (3). Ultrafiltration failure occurred in 4 infants who had to transfer to HD. Peritoneal dialysis is easier to establish, and the ability of automated PD to deliver short cycles, high dialysate flow rates, and high intraperitoneal volumes make it particularly good for the high fluid intake of the infant diet. Readers are referred S181

3 PROCEEDINGS OF THE 11TH CONGRESS OF THE ISPD JUNE 2007 VOL. 27, SUPPL 2 PDI to two excellent reviews of the practicalities of PD management in infants (7,18). Nutrition and Growth: Only during fetal life is growth as rapid as during infancy. Growth rates at birth can exceed 25 cm per year, falling to an average of 18 cm per year at 12 months of age, and 10 cm per year by the age of 2 years. Half of adult height is achieved by the age of 2 years, and so irrecoverable loss of growth potential can occur during this phase. Nutrition is particularly important during the infant phase, when growth is less dependent on growth hormone than during the childhood and pubertal phases. At birth, 170 kcal are stored in new tissue daily. That number falls to kcal at 6 months, kcal by 12 months, and kcal by the age of 2 years. These requirements can be difficult to achieve because of anorexia, vomiting, and episodes of poor intake attributable to infections and urologic procedures (19). Table 1 shows the U.K. daily dietary reference values for energy and protein for normal children and the recommendations for children on PD (19). There is no evidence to suggest that energy requirements for infants on PD should be any higher than those for normal children. Indeed up to 12 kcal/kg may be obtained daily from the glucose in dialysate, and that intake should be considered when calculating feed requirements (20). If the child is below the 2nd percentile for height, using the estimated average requirement for height age is advisable to ensure adequate energy intake. Protein requirements for infants on PD are higher than those for normal infants, and these young patients are at greater risk of protein malnutrition than are their peers treated with HD (21) because of an inverse correlation between peritoneal surface area and peritoneal protein losses. Infants have nearly twice the peritoneal protein losses per square meter of body surface area than do children weighing more than 50 kg. Such protein S182 TABLE 1 U.K. Dietary Reference Values for Normal Children (19) and Guidelines for Dietary Protein for Children on Peritoneal Dialysis (20) Age EAR energy RNI protein Protein intake for PD (months) (daily kcal/kg) (daily g/kg) (daily g/kg) Preterm EAR = estimated average requirement; RNI = recommended nutritional intake; PD = peritoneal dialysis. losses will impair normal growth if not replaced and may contribute to permanent loss of growth potential (22). Prescribing a protein supplement to reach the normal dietary requirement for all children on PD is therefore usual again using the recommended protein intake for height age if the child is below the 2nd percentile for height. Feeds can be based on a normal, complete, wheybased infant formula [SMA Gold (SMA Nutrition, Maidenhead, U.K.), Cow & Gate Premium (Nutricia, Trowbridge, U.K.)] or, rarely, a low-potassium feed [Kindergen PROD (SHS International, Liverpool, U.K.)], supplemented with energy either as a glucose polymer [Maxijul (SHS International) or Caloreen (Nestle, Vevey, Switzerland)] alone or in combination with a long-chain fat emulsion [Calogen (SHS International)] or a combined fat and carbohydrate product [Duocal (SHS International)]. Protein can be supplemented as a whey protein concentrate with amino acids [Maxipro (SHS International)]. The reader is referred to a review of nutrition for vitamin and mineral requirements (19). In many infants, achieving adequate intake is not possible without supplemental feeding, either by nasogastric tube or gastrostomy. Many infants with chronic renal failure have abnormal gastric motility, delayed gastric emptying, and gastroesophageal reflux, and as much as 30% of feeds may be lost with the associated vomiting (23). The use of ranitidine or prokinetic agents such as domperidone may help. However, if vomiting is so severe as to compromise nutrition, Nissen fundoplication and gastrostomy are indicated. In our center, more than 50% of infants on PD are managed with gastrostomies, and nearly 50% of those, with Nissen fundoplication (2,3). Complications of gastrostomy are uncommon, but include gastrocolic fistula and paraesophageal hernia. It is preferable to undertake gastrostomy before PD starts, because the risks of postsurgical peritonitis, exit-site infection, and dialysis catheter removal are increased if this surgery is undertaken after PD has started. The risk may be reduced if open surgery rather than percutaneous placement is used (24,25). After removal, the track usually closes spontaneously. RENAL OSTEODYSTROPHY Calcium requirements are relatively high in the rapidly growing infant. Also, care must be paid to the premature infant, who may have rickets of prematurity. Our center aims to maintain phosphate just below the 50th centile for age through dietary phosphate restriction [<400 mg (13 mmol) daily] and use of calcium carbon-

4 PDI JUNE 2007 VOL. 27, SUPPL 2 PROCEEDINGS OF THE 11TH CONGRESS OF THE ISPD ate or acetate. Parathyroid hormone is titrated against the lowest possible dose of activated vitamin D (0.01 µg/kg daily), with the aim of maintaining levels within the normal range as far as is achievable. In our infants, 79% had a parathyroid hormone level within the normal range after 1 year of PD (3). WHAT IS THE LONG-TERM OUTCOME? Mortality: The mortality rate in infants starting dialysis is as much as 4 times that of children beyond infancy (27), with most deaths occurring in the first year of life. A 1-year survival of about 85% was reported by the North American Pediatric Renal Transplant Cooperative Study and a U.K. series, as compared with 95% in children starting dialysis after infancy (2,28). That higher death rate persists, survival rates being 74% and 68% after 2 and 3 years respectively, as compared with 90% and 86% in children who start dialysis at older ages. No increase in mortality is observed in infants starting dialysis in the first month of life (8). Death may be attributable to treatment withheld, treatment withdrawn, or death on dialysis. Most infants in whom treatment is never started die within 1 year, and most of those deaths (more than 70%) occur in infants with associated comorbidity. A significant incidence of comorbidity (more than 50%) is also seen in patients in whom treatment is withdrawn; although, in some, the withdrawal occurs because of an unacceptably poor quality of life. Again, most of the deaths occur within 1 year. Causes of death in children actively treated with dialysis are similar to those reported in older children, predominantly sepsis or biochemical or fluidrelated disturbances, and no difference in outcome is evident in infants who are otherwise normal in comparison with older children (2,8). The life expectancy for these infants is unknown; it is possible that the complications that develop after years of RRT will simply occur at a proportionately earlier age. Growth: Severe growth retardation can occur even before an infant is referred to a pediatric nephrology service. Growth retardation can have a long-lasting effect on height potential. Approximately one third of the reduction in height occurs during fetal life. Another one third occurs during the first 3 months following birth and is accompanied by a similar decline in head circumference (29 31). However, infancy is when the potential for catch-up growth, with intensive nutritional input, is at its greatest. In 20 infants starting PD, we reported an improvement in height and weight standard deviation scores (SDSs) to, respectively, 1.1 and 0.3 at 1 year and 0.8 and 0.3 at 2 years from 1.8 and 1.6 at baseline (3). Over a similar time frame, 13 infants on PD showed a change in height SDS to 1.24 from 2.17 (2). Other centers have also reported catch-up growth in infants on PD, although an initial decline followed by stabilization of growth, no change, and a declining height SDS have also been reported (19). Poor nutritional status and growth are associated with starting PD at a younger age (32). Interestingly, infants who grew well continued with catch-up in early childhood (2,33). Development: Clearly, the developmental outcome is more likely to be adverse if renal failure is associated with a disorder such as neonatal hypoxia or certain syndromes and chromosomal abnormalities. Malnutrition can also compromise head growth; although, with intensive nutrition, an increase in head circumference to 1.3 at 6 months and 0.9 at 1 year from 1.9 at baseline was observed in our center s 20 infants (3). Overall, reports demonstrate relatively good outcomes. Of 28 survivors among 34 infants dialyzed before 3 months of age, only 1 was significantly delayed at 1 year of age. Of the 16 that reached 5 years of age, 15 were attending regular school (34). In our unit, 85% of infants had developmental scores within 2 standard deviations of the mean (mean IQ: 87), but 50% demonstrated borderline abnormal psychosocial adjustment (35). In a U.K. infant series of 105 children old enough to assess, 91 attended a regular school or were expected to, although 16 required individual support. The other 14 attended special schools, 11 for developmental and emotional needs and 3 for physical reasons (8). CONCLUSIONS It can be expected that, during childhood, approximately one third of infants with ESRF will die, nearly half will undergo transplantation, and the rest will have returned to dialysis. If survivors are to achieve the best possible outcomes, attention must be paid to nutrition, prevention of renal bone disease, preservation of dialysis access sites and the peritoneal membrane, and most importantly, provision of support to the families of these infants. REFERENCES 1. Geary DF. Attitudes of paediatric nephrologists to management of end-stage renal disease in infants. J Pediatr 1998; 133: Kari J, Gonzalez C, Ledermann SE, Shaw V, Rees L. Outcome and growth of infants with chronic renal failure. Kidney Int 2000; 57: S183

5 PROCEEDINGS OF THE 11TH CONGRESS OF THE ISPD JUNE 2007 VOL. 27, SUPPL 2 PDI 3. Ledermann SE, Scanes ME, Fernando ON, Duffy PG, Madden SJ, Trompeter RS. Long-term outcome of peritoneal dialysis in infants. J Pediatr 2000; 136: Bunchman TE. Infant dialysis: the future is now. J Pediatr 2000; 136: Ellis EN, Pearson D, Champion B, Wood EG. Outcomes of infants on chronic peritoneal dialysis. Adv Perit Dial 1995; 11: Shooter M, Watson A. The ethics of withholding and withdrawing dialysis therapy in infants. Pediatr Nephrol 2000; 14: Ronnholm KA, Holmberg C. Peritoneal dialysis in infants. Pediatr Nephrol 2006; 21: Coulthard MG, Crosier J. Outcome of reaching ESRF in children under 2 years of age. Arch Dis Child 2002; 87: Bunchman TE. The ethics of infant dialysis. Perit Dial Int 1996; 16(Suppl 1):S Rees L. Management of the infant with end-stage renal failure. Nephrol Dial Transplant 2002; 17: Ismaili K, Schurmans T, Wissing KM, Hall M, Van Aelst C, Janssen F. Early prognostic factors of infants with CRF caused by renal dysplasia. Pediatr Nephrol 2001; 16: Wood EG, Hand M, Briscoe DM, Donaldson LA, Yiu V, Harley FL, et al. Risk factors for mortality in infants and young children on dialysis. Am J Kidney Dis 2001; 37: Ellis EN, Pearson D, Champion B, Wood EG. Outcome of infants on chronic peritoneal dialysis. Adv Perit Dial 1995; 11: Verrina E, Zacchello G, Perfumo F, Edefonti A, Sorino P, Bassi S, et al. Clinical experience in the treatment of infants with chronic peritoneal dialysis. Adv Perit Dial 1995; 11: Coleman JE, Norman LJ, Watson AR. Provision of dietetic care in children on chronic peritoneal dialysis. J Ren Nutr 1999; 9: Becker T, Neipp M, Reichart B, Pape L, Ehrich J, Klempnauer J, et al. Paediatric kidney transplantation in small children a single centre experience. Transpl Int 2006; 19: Shroff R, Wright E, Ledermann S, Hutchinson C, Rees L. Chronic hemodialysis in infants and children under 2 years of age. Pediatr Nephrol 2003; 18: Flynn JT, Warady BA. Peritoneal dialysis in children: challenges for the new millennium. Adv Ren Replace Ther 2000; 7: Rees L, Shaw V. Nutrition in children with CRF and on dialysis. Pediatr Nephrol 2007; [In press]. 20. K/DOQI, National Kidney Foundation. Clinical practice guidelines for nutrition in chronic renal failure. Am J Kidney Dis 2000; 35(Suppl 2):S Brem AS, Lambert C, Hill C, Kitsen J, Shemin DG. Prevalence of protein malnutrition in children maintained on peritoneal dialysis. Pediatr Nephrol 2002; 17: Quan A, Baum M. Protein losses in children on continuous cycler peritoneal dialysis. Pediatr Nephrol 1996; 10: Ledermann SE, Shaw V, Trompeter RS. Long-term enteral nutrition in infants and young children with CRF. Pediatr Nephrol 1999; 13: Ledermann SE, Spitz L, Moloney J, Rees L, Trompeter RS. Gastrostomy feeding in infants and children on peritoneal dialysis. Pediatr Nephrol 2002; 17: Ramage IJ, Harvey E, Geary DF, Hebert D, Balfe JA, Balfe JW. Complications of gastrostomy feeding in children receiving peritoneal dialysis. Pediatr Nephrol 1999; 13: McDonald SP, Craig JC, for the Australian and New Zealand Paediatric Nephrology Association. Long-term survival of children with end-stage renal disease. N Engl J Med 2004; 350: Shroff R, Rees L, Trompeter R, Hutchinson C, Ledermann S. Long-term outcome of chronic dialysis in children. Pediatr Nephrol 2006; 21: Neu AM, Ho PL, McDonald RA, Warady BA. Chronic dialysis in children and adolescents. The 2001 annual report of the NAPRTCS. Pediatr Nephrol 2002; 17: Karlberg J, Schaefer F, Hennicke M, Wingen AM, Rigden S, Mehls O. Early age-dependent growth impairment in chronic renal failure. European Study Group for Nutritional Treatment of CRF in Childhood. Pediatr Nephrol 1996; 10: Van Dyck M, Proesmans W. Head circumference in CRF from birth. Clin Nephrol 2001; 56:S Rizzoni G, Basso T, Setari M. Growth in children with chronic renal failure on conservative treatment. Kidney Int 1984; 26: Edefonti A, Paglialonga F, Picca M, Perfumo F, Verrina E, Lavoratti G, et al. A prospective multicentre study of the nutritional status in children on chronic peritoneal dialysis. Nephrol Dial Transplant 2006; 21: Kleinknecht C, Broyer M, Huot D, Marti Henneberg C, Dartois AM. Growth and development of nondialyzed children with chronic renal failure. Kidney Int 1983; 24(Suppl 15):S Warady BA, Belden B, Kohaut E. Neurodevelopmental outcome of children initiating peritoneal dialysis in early infancy. Pediatr Nephrol 1999; 13: Madden SJ, Ledermann SE, Guerrero Blanco M, Bruce M, Trompeter RS. Cognitive and psychosocial outcome of infants dialysed in infancy. Child Care Health Dev 2003; 29: S184