Survival and clinical outcomes of children starting renal replacement therapy in the neonatal period
2014; Elsevier BV; Volume: 86; Issue: 1 Linguagem: Inglês
10.1038/ki.2013.561
ISSN1523-1755
AutoresKarlijn J. van Stralen, Dagmara Borzych–Dużałka, Hiroshi Hataya, Seán Kennedy, Kitty J. Jager, Enrico Verrina, Carol Inward, Kai Rönnholm, Karel Vondrák, Bradley A. Warady, Aleksandra Żurowska, Franz Schaefer, Pierre Cochat,
Tópico(s)Neonatal Health and Biochemistry
ResumoEnd-stage renal disease requiring renal replacement therapy (RRT) during the neonatal period is a very rare condition, and little information is available regarding long-term RRT and outcomes. To gain more information, we performed a collaborative study on patient characteristics and treatment outcomes in children who started RRT as neonates during their first month of life between 2000 and 2011 who were prospectively registered in the ESPN/ERA-EDTA, the IPPN (since 2007), the Japanese registry, or the Australian and New Zealand Dialysis and Transplant (ANZDATA) registry. During the first month of life, 264 patients from 32 countries started RRT and were followed for a median of 29 months (interquartile range 11–60 months). Most neonates (242) started on peritoneal dialysis, 21 started on hemodialysis, and 1 patient with a transplant. The most important causes of renal failure were congenital anomalies of the kidney and urinary tract in 141, cystic kidneys in 35, and cortical necrosis in 30. Within 2 years after the start of RRT, 69 children changed dialysis modality and 53 received a renal transplant. After a median of 7 months, 45 children had died, mainly because of infection, resulting in an estimated 2-year survival of 81%, and 5-year survival of 76%. Growth retardation (63%), anemia (55%), and hypertension (57%) were still major problems after 2 years. Thus, relatively good medium-term patient survival may be achieved with RRT started during the neonatal period, but specific therapeutic challenges continue to exist in this age group. End-stage renal disease requiring renal replacement therapy (RRT) during the neonatal period is a very rare condition, and little information is available regarding long-term RRT and outcomes. To gain more information, we performed a collaborative study on patient characteristics and treatment outcomes in children who started RRT as neonates during their first month of life between 2000 and 2011 who were prospectively registered in the ESPN/ERA-EDTA, the IPPN (since 2007), the Japanese registry, or the Australian and New Zealand Dialysis and Transplant (ANZDATA) registry. During the first month of life, 264 patients from 32 countries started RRT and were followed for a median of 29 months (interquartile range 11–60 months). Most neonates (242) started on peritoneal dialysis, 21 started on hemodialysis, and 1 patient with a transplant. The most important causes of renal failure were congenital anomalies of the kidney and urinary tract in 141, cystic kidneys in 35, and cortical necrosis in 30. Within 2 years after the start of RRT, 69 children changed dialysis modality and 53 received a renal transplant. After a median of 7 months, 45 children had died, mainly because of infection, resulting in an estimated 2-year survival of 81%, and 5-year survival of 76%. Growth retardation (63%), anemia (55%), and hypertension (57%) were still major problems after 2 years. Thus, relatively good medium-term patient survival may be achieved with RRT started during the neonatal period, but specific therapeutic challenges continue to exist in this age group. Although the need for renal replacement therapy (RRT) for end-stage renal disease in children less than 2 years of age occurs at an incidence of 7.1–8.3 per million age-related population (pmarp) (Orr et al.1.Orr N.I. McDonald S.P. McTaggart S. et al.Frequency, etiology and treatment of childhood end-stage kidney disease in Australia and New Zealand.Pediatr Nephrol. 2009; 24: 1719-1726Crossref PubMed Scopus (51) Google Scholar and ESPN/ERA-EDTA registry, personal communication), the number of neonates requiring RRT is extremely small. Issues with children who start RRT in the first month of life are different from those who start at a later stage. A comparison between neonates and children who start RRT between the age of 1 month and 2 years revealed similar race and gender distributions but different causes of renal failure, different treatment options, and a higher rate of hospitalization.2.Carey W.A. Talley L.I. Sehring S.A. et al.Outcomes of dialysis initiated during the neonatal period for treatment of end-stage renal disease: a North American Pediatric Renal Trials and Collaborative Studies special analysis.Pediatrics. 2007; 119: e468-e473Crossref PubMed Scopus (87) Google Scholar In another small study, no differences were found with respect to height or body weight s.d. scores.3.Coulthard M.G. Crosier J. Outcome of reaching end stage renal failure in children under 2 years of age.Arch Dis Child. 2002; 87: 511-517Crossref PubMed Scopus (52) Google Scholar A particular problem with assessing the demographics of end-stage renal disease in this age group is that RRT is not offered to all children in whom it might be required.4.Geary D.F. Attitudes of pediatric nephrologists to management of end-stage renal disease in infants.J Pediatr. 1998; 133: 154-156Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar Decisions concerning starting RRT in neonates are based on local resources and background, patient comorbidities, anticipated quality of life, and family acceptance.5.Fauriel I. Moutel G. Moutard M.L. et al.Decisions concerning potentially life-sustaining treatments in paediatric nephrology: a multicentre study in French-speaking countries.Nephrol Dial Transplant. 2004; 19: 1252-1257Crossref Scopus (26) Google Scholar Improvement of technology together with evolving social acceptance of disabilities has led to significant changes in medical and ethical decision-making during the past decades. In a recent international survey, 98% of pediatric nephrologists offered RRT at least in some infants younger than 1 month of age, and 30% offered treatment to all infants with end-stage renal disease.6.Teh J.C. Frieling M.L. Sienna J.L. et al.Attitudes of caregivers to management of end-stage renal disease in infants.Perit Dial Int. 2011; 31: 459-465Crossref PubMed Scopus (44) Google Scholar In a previous survey from the same authors in 1998, 80% of pediatric nephrologists considered that parental rights to refuse RRT for their child were acceptable.4.Geary D.F. Attitudes of pediatric nephrologists to management of end-stage renal disease in infants.J Pediatr. 1998; 133: 154-156Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar In another survey among French-speaking pediatric intensivists and nephrologists in 2001, starting RRT in neonates was well accepted in only 9% of neonatal units and systematically rejected by 24%; 24% of the neonatal units were moderately in favor of starting RRT, whereas 35% preferred treatment withdrawal.7.Burguet A. Abraham-Lerat L. Cholley F. et al.[Terminal and pre-terminal chronic renal insufficiency in newborns in French neonatal intensive care units: survey of the French pediatric nephrologic society of resuscitation and emergency].Arch Pediatr. 2002; 9: 489-494Crossref Scopus (7) Google Scholar Quality of life, family circumstances, parental rights, and the child’s prognosis are the main criteria applied in decision-making.8.Cochat P. Ranchin B. Ethics and maintenance dialysis in children.in: Warady B. Schaefer F. Alexander S.R. Pediatric Dialysis. Springer, 2012Google Scholar To make an informed judgment, for both the attending physicians and the patient’s family, information on the future prospects of these children is essential and requires up-to-date, unbiased outcome data from a large group of patients. To overcome the challenge of the low incidence of neonatal RRT, we performed a collaborative study on patient characteristics and treatment outcomes in children who started RRT at neonatal age. We undertook an unprecedented global effort to obtain a sufficiently sized, representative and recent patient sample for analysis, combining data from national and international pediatric RRT registries covering 40 countries. A total of 264 patients (64.8% male) from 32 countries started RRT during the first month of life. Including data from those countries in which no neonates were started on RRT but which had complete population-wide coverage for a particular period, neonates represented 18.3% of the population of infants (<2 years) among Western European countries, 18.1% among Eastern European countries, whereas this was 6.8% in Australia and New Zealand and 8.6% of all <5-year-olds in Japan. Half of the neonates started RRT in their first week of life (51%). The most common causes of renal failure were congenital anomalies of the kidney and urinary tract (CAKUT, 54.6%), followed by cystic kidneys (13.3%, of which 80% autosomal recessive polycystic kidney disease (ARPKD) and the remainder medullary cystic kidney disease) and cortical necrosis (11.4%) (Table 1). The first RRT modality was peritoneal dialysis (PD) in 91.7%, whereas 8.0% of neonates started on hemodialysis (HD), and a single patient (0.4%) started with a transplant. There were no marked differences with respect to gender, cause of renal failure, or week of start between the patients starting with PD versus HD.Table 1Patient characteristics at the start of RRTPatients, N=264 (%)Data source ESPN/ERA-EDTA registry202a20 Patients are in both registries. IPPN60a20 Patients are in both registries. Japan18 ANZDATA4Age at start of RRT Days 1–7141 (53.4%) Days 8–1457 (21.6%) Days 15–2132 (12.2%) Days 22–3134 (12.9%)Gender Male171 (64.8%)Treatment modality at the start of RRT PD242 (91.7%) HD21(8.0%) Tx1 (0.4%)Primary disease Congenital anomalies of the kidney and urinary tract144 (54.6%) Cystic kidney disease35 (13.3%) Cortical necrosis30 (11.4%) Renal vascular disease9 (3.4%) Congenital nephrotic syndrome15 (5.7%) Hemolytic uremic syndrome3 (1.1%) Angiotensin-receptor blockade fetopathy3 (1.1%) Oxalosis2 (0.8%) Other not specified23 (8.7%)Abbreviations: HD, hemodialysis; PD, peritoneal dialysis; RRT, renal replacement therapy; Tx, transplantatio.a 20 Patients are in both registries. Open table in a new tab Abbreviations: HD, hemodialysis; PD, peritoneal dialysis; RRT, renal replacement therapy; Tx, transplantatio. Patients were followed up for a median of 28.6 (interquartile range 11–60) months. During 2 years of follow-up 45 patients died, resulting in a 2-year survival rate of 81.2% (Figure 1). All patients, besides four, died on dialysis. The 5-year survival rate was 76.4%. Among the patients who died during the first 2 years, the median time to death was 7.2 months (interquartile range 3–10 months), and all patients except 7 died in the first year of life. The main causes of death were infection (n=16, 35.6%) and cardiac arrest (n=4, 8.9%), but they were unknown in many cases (Table 2). There were no significant differences in the risk of death regarding week of RRT initiation, initial treatment modality, gender, underlying renal disease, birth weight, registries, and countries. Whereas the overall survival rate was independent of the presence or absence of comorbidities, concomitant neurological disorders increased the risk of death fivefold (hazard ratio 5.2, 95% confidence interval 1.7–15.4, P=0.003).Table 2Causes of death among those dying within 2 years after the start of RRTPatients, N=45Infection16 (35.6%)Cardiac arrest4Hemorrhage2Withdrawal1Lung hypoplasia/pulmonary edema4Unknown/missing18 Open table in a new tab During the first 2 years of life, 39.4% of the patients switched the treatment modality (excluding death and recovery of renal function). The treatment distribution every 6 months between 0 and 5 years is shown in Figure 2a, whereas the first two changes in treatment modality are depicted in Figure 2b. Forty-five patients received a transplant within the first 2 years after birth (Figure 1), and the median time to transplantation in this group was 17.5 (p5–p95 14.3–20) months. For eight patients (18%), height and weight at transplantation in the first 2 years was available. Median height was 75cm, ranging from 49.5 to 79cm, and weight was 9.6kg, ranging from 3.1 to 11.6kg. At that point, 22 patients had received a renal allograft from a living donor, 18 from a deceased donor, and the donor source was unknown in 5 cases. At 5 years, 99 patients had received a transplant after a median of 25 (p5–p95 12.1–53.9) months, and 4 patients had received two renal allografts after failure of their first graft. Median length and weight at transplantation were 89.6cm and 13.6kg, respectively, when all transplants performed within the first 5 years were considered (based on 22 patients). After 2 years and 5 years, 21.9% and 54.9% of all patients who started had received a transplant, respectively (including the patients who died), whereas among all patients still alive after 5 years 68.2% were living with a functioning graft. Of all transplanted patients, four died (one after a second transplantation) and seven lost their graft within 5 years after transplantation, resulting in a 5-year patient and graft survival of 84.2%. A single patient with congenital focal and segmental glomerulosclerosis received a transplant on the fourth day of life, at 49.5cm length and 3.1kg body weight; she died on the subsequent day. Fifteen patients showed recovery of their renal function, which turned out to be transient in at least two cases. Their main causes of renal failure were cortical necrosis (n=6) and renal hypo/dysplasia (n=5), which was significantly different from the children who did not recover. Eight patients who recovered had started in the first week of life, 4 had started in the second week, and 3 in the third week, which was not significantly different from the children who did not recover. The median time from RRT start to recovery of renal function was 10.8 months (range <1 to 40 months). In the first year after starting RRT, 73% of the patients were reported to have comorbidities. Among the patients in whom information was available in the first year after the start of RRT, 20% had neurodevelopmental delay, 12% of the patients had pulmonary alterations (primarily pulmonary hypoplasia), and another 18% had cardiovascular disorders (Table 3).Table 3Comorbidities reported in the first year after the start of RRTAny comorbidityYes81/111 (73%)Type of comorbid conditionsDevelopmental delay22/110(20%)Cardiovascular disorder17/92 (18%)Lung abnormality involvement (including pulmonary hypoplasia)11/92 (12%)Neurological disorder22/92 (24%)Liver disease18/76 (24%)Birth weight (n=105)Median (interquartile range)2869 (2309–3450)gSerum creatinine at the start of RRT (n=126)Median (interquartile range)3.9 (2.9–5.2) mg/dleGFR at the start (n=76)Median (interquartile range)5.5 (4.0–7.0) ml/min per 1.73m2Residual renal output at PD initiation (n=24)Median (interquartile range)87.5 (0–350) ml/dayAbbreviations: eGFR, estimated glomerular filtration rate; PD, peritoneal dialysis; RRT, renal replacement therapy.Numbers indicate the fraction of affected patients relative to the number of patients in whom this information was reported (%). Open table in a new tab Abbreviations: eGFR, estimated glomerular filtration rate; PD, peritoneal dialysis; RRT, renal replacement therapy. Numbers indicate the fraction of affected patients relative to the number of patients in whom this information was reported (%). RRT was started at a median estimated glomerular filtration rate (eGFR) of 5.5ml/min per 1.73m2 and interquartile range of 4.0–73.0. Serum creatinine values were 3.9mg/dl, with an interquartile range of 2.9–5.2. Residual renal output was 88ml per 24h, with an interquartile range of 0–208. Of the patients in whom information was available, 29% were anuric at the start of RRT and 8% had a residual renal output of 1.64). The prevalence of hypertension was not affected by the cause of renal failure, treatment type, or the presence or absence of comorbidities. Female patients had significantly lower systolic blood pressure (-0.63, 95% CI -1.10 to –0.17) as compared with males. In the first 6 months, 23.5% of the patients received antihypertensive medication, increasing to 42% in the second year. Hemoglobin levels decreased from 11.6g/dl (95% CI 10.5–12.6) at birth to 10.0g/dl (95% CI 8.9–11.2) at 4 months, which is similar to the decline in the normal population, and remained stable thereafter (mean 10.8g/dl) (Figure 3d). After 2 years, 64% of the patients were still anemic. Patients on HD had significantly lower hemoglobin levels (mean difference -1.18g/dl (95% CI -2.0 to -0.37, P<0.05)) as compared with patients on PD. Hemoglobin levels were even lower among patients who had switched from PD to HD than among patients maintained on HD. No differences were observed between gender, cause of renal failure, or the presence or absence of comorbidities. The use of erythropoiesis-stimulating agents was consistent over time, with 79% of the patients treated in the first 6 months and 86% in the second year. Serum albumin levels increased linearly over time from 31.6g/l shortly after birth to 35.8g/l after 2 years of age. No differences were observed between gender, treatment modality, or cause of renal failure, but patients without comorbidities had significantly higher albumin levels (difference 4.4g/l, 95% CI 0.2–8.6). Remarkably good medium-term patient survival is achieved in neonates in whom a decision in favor of RRT has been made and who were subsequently registered in one of the registries participating in this study. However, arterial hypertension, growth retardation, and the common presence of comorbidities constitute major challenges. As in other studies, the causes of severe renal impairment in this specific age group mainly include CAKUT, ARPKD, bilateral renal vein thrombosis, congenital nephrotic syndrome, inherited renal tubular dysgenesis, and primary hyperoxaluria.9.Lau K.K. Stoffman J.M. Williams S. et al.Neonatal renal vein thrombosis: review of the English-language literature between 1992 and 2006.Pediatrics. 2007; 120: e1278-e1284Crossref PubMed Scopus (127) Google Scholar, 10.Wedekin M. Ehrich J.H. Offner G. et al.Renal replacement therapy in infants with chronic renal failure in the first year of life.Clin J Am Soc Nephrol. 2010; 5: 18-23Crossref PubMed Scopus (39) Google Scholar, 11.Cochat P. Koch Nogueira P.C. Mahmoud M.A. et al.Primary hyperoxaluria in infants: medical, ethical, and economic issues.J Pediatr. 1999; 135: 746-750Abstract Full Text Full Text PDF PubMed Scopus (68) Google Scholar Recent series in children starting RRT during the first year of life have suggested that chances of survival are now excellent, and RRT should be offered to all infants unless major extrarenal comorbidities are present.1.Orr N.I. McDonald S.P. McTaggart S. et al.Frequency, etiology and treatment of childhood end-stage kidney disease in Australia and New Zealand.Pediatr Nephrol. 2009; 24: 1719-1726Crossref PubMed Scopus (51) Google Scholar,10.Wedekin M. Ehrich J.H. Offner G. et al.Renal replacement therapy in infants with chronic renal failure in the first year of life.Clin J Am Soc Nephrol. 2010; 5: 18-23Crossref PubMed Scopus (39) Google Scholar,12.Samuel S.M. Tonelli M.A. Foster B.J. et al.Survival in pediatric dialysis and transplant patients.Clin J Am Soc Nephrol. 2011; 6: 1094-1099Crossref PubMed Scopus (61) Google Scholar,13.Hijazi R. Abitbol C.L. Chandar J. et al.Twenty-five years of infant dialysis: a single center experience.J Pediatr. 2009; 155: 111-117Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar However, very few studies have analyzed children commencing RRT during the first month of life. Although early series found medium-term patient survival rates (i.e.,≥2 years) around 50%,10.Wedekin M. Ehrich J.H. Offner G. et al.Renal replacement therapy in infants with chronic renal failure in the first year of life.Clin J Am Soc Nephrol. 2010; 5: 18-23Crossref PubMed Scopus (39) Google Scholar,13.Hijazi R. Abitbol C.L. Chandar J. et al.Twenty-five years of infant dialysis: a single center experience.J Pediatr. 2009; 155: 111-117Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar,14.Rheault M.N. Rajpal J. Chavers B. et al.Outcomes of infants <28 days old treated with peritoneal dialysis for end-stage renal disease.Pediatr Nephrol. 2009; 24: 2035-2039Crossref PubMed Scopus (29) Google Scholar 75% 2-year survival was documented in a more recent larger series.2.Carey W.A. Talley L.I. Sehring S.A. et al.Outcomes of dialysis initiated during the neonatal period for treatment of end-stage renal disease: a North American Pediatric Renal Trials and Collaborative Studies special analysis.Pediatrics. 2007; 119: e468-e473Crossref PubMed Scopus (87) Google Scholar In our series of 264 patients collected around the globe, the 2-year patient survival exceeded 80%. This is only slightly worse than the survival among infants, which was 89.8% in the ESPN/ERA-EDTA Registry. In keeping with previous experience, infections and ‘cardiac arrest’ (putatively related to congestive heart failure and/or electrolyte imbalances) were the main causes of death in this age group.15.Mekahli D. Shaw V. Ledermann S.E. et al.Long-term outcome of infants with severe chronic kidney disease.Clin J Am Soc Nephrol. 2010; 5: 10-17Crossref PubMed Scopus (69) Google Scholar,16.Ledermann S.E. Scanes M.E. Fernando O.N. et al.Long-term outcome of peritoneal dialysis in infants.J Pediatr. 2000; 136: 24-29Abstract Full Text Full Text PDF PubMed Scopus (131) Google Scholar Other critical conditions common to neonatal renal failure and its treatment, such as pulmonary hypoplasia, hemorrhage, or intractable fluid imbalance, did not appear to affect survival to a major degree in our series. Notably, the presence of comorbidities did not affect patient survival, except for neurological disorders, which increased the risk of death fivefold. We cannot exclude some selection bias underlying the apparent lack of impact of comorbidities, as treatment may not have been offered to neonates with most severe comorbidities in whom reasonable chances of survival and quality of life could not be expected. PD clearly is the treatment modality of first choice in this age group.17.Zurowska A.M. Fischbach M. Watson A.R. et al.Clinical practice recommendations for the care of infants with stage 5 chronic kidney disease (CKD5).Pediatr Nephrol. 2013; 28: 1739-1748Crossref PubMed Scopus (66) Google Scholar Owing to major anatomical and technical challenges, HD has very limited indications during infancy, such as recent abdominal surgery or primary hyperoxaluria.11.Cochat P. Koch Nogueira P.C. Mahmoud M.A. et al.Primary hyperoxaluria in infants: medical, ethical, and economic issues.J Pediatr. 1999; 135: 746-750Abstract Full Text Full Text PDF PubMed Scopus (68) Google Scholar HD was performed as primary RRT in 21 children in this study; notably, their outcomes were similar to children started on PD, except for a higher prevalence of hypertension and anemia. Pre-emptive kidney transplantation cannot be advised in neonates, as there are no successful reports in this age group, as was also shown in this study. However, transplantation at a later stage, i.e., in children older than 1 year of age, shows promising results, as 5-year graft survival rates of 83–98% have been reported,3.Coulthard M.G. Crosier J. Outcome of reaching end stage renal failure in children under 2 years of age.Arch Dis Child. 2002; 87: 511-517Crossref PubMed Scopus (52) Google Scholar,5.Fauriel I. Moutel G. Moutard M.L. et al.Decisions concerning potentially life-sustaining treatments in paediatric nephrology: a multicentre study in French-speaking countries.Nephrol Dial Transplant. 2004; 19: 1252-1257Crossref Scopus (26) Google Scholar,7.Burguet A. Abraham-Lerat L. Cholley F. et al.[Terminal and pre-terminal chronic renal insufficiency in newborns in French neonatal intensive care units: survey of the French pediatric nephrologic society of resuscitation and emergency].Arch Pediatr. 2002; 9: 489-494Crossref Scopus (7) Google Scholar,10.Wedekin M. Ehrich J.H. Offner G. et al.Renal replacement therapy in infants with chronic renal failure in the first year of life.Clin J Am Soc Nephrol. 2010; 5: 18-23Crossref PubMed Scopus (39) Google Scholar,18.Davis I.D. Chang P.N. Nevins T.E. Successful renal transplantation accelerates development in young uremic children.Pediatrics. 1990; 86: 594-600PubMed Google Scholar which are similar to our results of 84.2%. Those infants who survive for transplantation will have similar long-term outcomes as older kidney recipients, and in fact will have a better long-term graft survival than teenagers.10.Wedekin M. Ehrich J.H. Offner G. et al.Renal replacement therapy in infants with chronic renal failure in the first year of life.Clin J Am Soc Nephrol. 2010; 5: 18-23Crossref PubMed Scopus (39) Google Scholar,14.Rheault M.N. Rajpal J. Chavers B. et al.Outcomes of infants <28 days old treated with peritoneal dialysis for end-stage renal disease.Pediatr Nephrol. 2009; 24: 2035-2039Crossref PubMed Scopus (29) Google Scholar,19.Chavers B. Najarian J.S. Humar A. Kidney transplantation in infants and small children.Pediatr Transplant. 2007; 11: 702-708Crossref PubMed Scopus (33) Google Scholar eGFR at the start of RRT was very low—much lower than in the total pediatric population commencing RRT.20.van Stralen K.J. Tizard E.J. Jager K.J. et al.Determinants of eGFR at start of renal replacement therapy in paediatric patients.Nephrol Dial Transplant. 2010; 25: 3325-3332Crossref PubMed Scopus (33) Google Scholar Although the low starting level may partly reflect the physiologically lower GFR in the first month of life, dialysis was initiated owing to oligoanuria in 38% of the patients in whom this information was available, demonstrating an absolute need for RRT. Still, renal function later recovered in 6% of the cohort, indicating that partially reversible prolonged acute kidney injury was present in a few children. The observed number of patients with a low eGFR might even be an underestimate in view of the high prevalence of neonatal hyperbilirubinemia, which tends to interfere with the Jaffe method leading to artifactually low serum creatinine and falsely higher GFR estimates. Unfortunately, no information on the type of assay used was available. Furthermore, the creatinine assays in different laboratories may not have been validated against isotope dilution mass spectrometry standards and national standardization, possibly resulting in nondifferential misclassification of the eGFR values. Many children in our population were already relatively short at birth, with 43% being growth retarded. Part of this might be explained by the lack of sufficient data on gestational age, but these data are in keeping with previous analyses of birth length in children with CAKUT and support the hypothesis that certain adverse intrauterine conditions may lead to both impaired fetal growth and kidney hypoplasia.21.Bacchetta J. Harambat J. Dubourg L. et al.Both extrauterine and intrauterine growth restriction impair renal function in children born very preterm.Kidney Int. 2009; 76: 445-452Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar, 22.Rees L. Management of the infant with end-stage renal failure.Nephrol Dial Transplant. 2002; 17: 1564-1567Crossref PubMed Scopus (45) Google Scholar, 23.Schaefer F. Wingen A.M. Hennicke M. et al.Growth charts for prepubertal children with chronic renal failure due to congenital renal disorders. European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood.Pediatr Nephrol. 1996; 10: 288-293Crossref PubMed Scopus (63) Google Scholar Furthermore, early postnatal growth faltered. Growth failure occurred despite adequate, possibly aggressive, nutrition evidenced by high average BMI during the observation period. Subsequent to this early period of growth failure, the patients retained their line on the growth curve around -2.5 z-scores. This growth pattern is in keeping with recent findings obtained in a large cohort of children commencing dialysis during the first 2 years of life,22.Rees L. Management of the infant with end-stage renal failure.Nephrol Dial Transplant. 2002; 17: 1564-1567Crossref PubMed Scopus (45) Google Scholar but slightly worse than another small study where (after an unknown period of time) the mean height z-score was -1.673.Coulthard M.G. Crosier J. Outcome of reaching end stage renal failure in children under 2 years of age.Arch Dis Child. 2002; 87: 511-517Crossref PubMed Scopus (52) Google Scholar, and lends further support to the notion that adequate nutrition is necessary but frequently not sufficient to establish normal or even catch-up growth in dialyzed infants.24.Laakkonen H. Happonen J.M. Marttinen E. et al.Normal growth and intravascular volume status with good metabolic control during peritoneal dialysis in infancy.Pediatr Nephrol. 2010; 25: 1529-1538Crossref Scopus (15) Google Scholar The impaired birth length and early postnatal growth may also support the hypothesis formulated by Karlberg et al.25.Karlberg J. Schaefer F. Hennicke M. et al.Early age-dependent growth impairment in chronic renal failure. European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood.Pediatr Nephrol. 1996; 10: 283-287Crossref PubMed Scopus (78) Google Scholar that children with renal hypodysplasia may be subject to intrauterine programming toward reduced length gain in the ‘Infancy’ growth phase encompassing late fetal and early postnatal life. Hemoglobin levels followed the pattern of normal children, with high perinatal concentrations sharply decreasing to a nadir around the age of 4 months, followed by a gradual subsequent increase. However, children on RRT had lower hemoglobin levels than the normal pediatric population, and the mean was below that generally considered as anemia, despite the use of erythropoiesis-stimulating agents. Arterial hypertension appears to be an important and perhaps under-recognized comorbidity in this age group. On average 51% of the patients exhibited systolic and/or diastolic hypertension during the 3 years of follow-up, which is in line with our previous study from the ESPN/ERA-EDTA Registry demonstrating in this age group. Uncontrolled hypertension is more common in the infant age group than in older children and adolescents.26.Kramer A.M. van Stralen K.J. Jager K.J. et al.Demographics of blood pressure and hypertension in children on renal replacement therapy in Europe.Kidney Int. 2011; 80: 1092-1098Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar Our study—similar to other studies—is subject to selection bias, as patients in whom treatment was not started were not included. Indeed, in addition to severe urinary tract malformation leading to pregnancy termination, live-born infants in whom a decision was made to withhold, or withdraw, renal support early on escaped inclusion by default. Furthermore, some children who died very soon after the start of RRT before entering the chronic treatment program might have gone unreported. Such exclusions would lead to an overestimation of survival rates. On the other hand, infants who recovered their renal function to a degree allowing discontinuation of dialysis within, or soon after, the neonatal period might also have gone under-reported, leading to a possible underestimation of survival rates. We also only have limited data on comorbidities, complications, and hospitalizations. RRT in neonates is a highly specialized and resource-intense therapy and it is likely that many surviving neonates spent considerable time as hospital in-patients. The financial burden and the ‘social cost’ to the families cannot be determined from our study. Another limitation of the study is the heterogeneous patient population. Data were combined from four different registries, all collecting data in different manners. Starting RRT in newborn infants is a demanding procedure that raises both ethical and technical challenges to pediatric nephrologists and neonatologists, caregivers, and parents. This multi-registry report on 214 patients provides the most extensive information on RRT in neonates to date and suggests that despite potentially life-limiting extra-renal comorbidities medium-term survival in patients in whom the decision to commence RRT is made is rather favorable. Within 2 years, 82.7% of the patients were alive and 20% of the cohort were living with a renal allograft. We identified specific therapeutic challenges in this age group such as life-threatening infections, growth failure, and hypertension. Our findings may facilitate clinical decision-making in cases of severe renal impairment diagnosed either prenatally or immediately after birth.
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