Tuula Hölttä

Clinical outcome of pediatric patients on peritoneal dialysis under adequacy control

Abstract Clinical outcome under adequacy control was studied in 10 pediatric patients under 5 years and 11 patients over 5 years of age on continuous peritoneal dialysis (PD). Outcome was compared between the age groups and with our previous results in patients under 5 years of age. Peritoneal equilibration test and 24-h dialysate collection were performed. Laboratory data, clinical status, and diet were recorded. PD prescription was adjusted for these parameters. The mean weekly urea Kt/V was similar and stable in the two age groups (3.1±0.6 vs. 3.2±0.4 at baseline). The mean weekly creatinine clearance (CCr) was at baseline significantly lower in the younger age group (58.7±11.9 vs. 78.0±14.9 l/week per 1.73 m2, P=0.004), but later similar. Urea Kt/V and CCr correlated significantly. Hematological and biochemical parameters were stable, and catch-up growth was observed in 62% of the patients during 9 months of follow-up. The outcome for children under and over 5 years of age did not differ significantly. The clinical outcome in patients under 5 years of age improved under adequacy control, when compared with our previous results in patients of the same age. This suggests a positive effect of adequacy control on clinical outcome.

Renal manifestations of Henoch–Schönlein purpura in a 6-month prospective study of 223 children

Objective To assess the risk factors for developing Henoch–Schönlein purpura nephritis (HSN) and to determine the time period when renal involvement is unlikely after the initial disease onset. Design A prospective study of 223 paediatric patients to examine renal manifestations of Henoch–Schönlein purpura (HSP). The patients condition was monitored with five outpatient visits to the research centre and urine dipstick testing at home. Results HSN occurred in 102/223 (46%) patients, consisting of isolated haematuria in 14%, isolated proteinuria in 9%, both haematuria and proteinuria in 56%, nephrotic-range proteinuria in 20% and nephrotic-nephritic syndrome in 1%. The patients who developed HSN were significantly older than those who did not (8.2±3.8 vs 6.2±3.0 years, p<0.001, CI for the difference 1.1 to 2.9). Nephritis occurred a mean of 14 days after HSP diagnosis, and within 1 month in the majority of cases. The risk of developing HSN after 2 months was 2%. Prednisone prophylaxis did not affect the timing of the appearance of nephritis. The risk factors for developing nephritis were age over 8 years at onset (OR 2.7, p=0.002, CI 1.4 to 5.1), abdominal pain (OR 2.1, p=0.017, CI 1.1 to 3.7) and recurrence of HSP disease (OR 3.1, p=0.002, CI 1.5 to 6.3). Patients with two or three risk factors developed nephritis in 63% and 87% of cases, respectively. Laboratory tests or blood pressure measurement at onset did not predict the occurrence of nephritis. Conclusion The authors recommend weekly home urine dipstick analyses for the first 2 months for patients with HSP. Patients with nephritis should be followed up for more than 6 months as well as the patients with HSP recurrence.

Clinical course of extrarenal symptoms in Henoch–Schönlein purpura: a 6-month prospective study

Objective To describe the extrarenal symptoms and clinical course of Henoch–Schönlein purpura (HSP). Design A prospective national multicentre trial with 6-month follow-up. Patients A total of 223 newly diagnosed paediatric HSP patients. Results Purpura was the initial symptom in 73% of the patients and was preceded by joint or gastrointestinal manifestations in the rest by a mean of 4 days. Joint symptoms, abdominal pain, melena, nephritis and recurrences occurred in 90%, 57%, 8%, 46% and 25% of the patients, respectively. Orchitis affected 17/122 (14%) of the boys. Seven patients developed protein-losing enteropathy characterised by abdominal pain, oedema and serum albumin under 30 g/l, and an additional 49 patients had subnormal albumin levels without any proteinuria. Positive fecal occult blood (26/117, 22%) and α1-antitrypsin (7/77, 9%) suggested mucosal injury even in the patients without gastrointestinal symptoms. HSP was often preceded by various bacterial, especially streptococcal (36%) and viral infections. Previous streptococcal infection did not induce changes in the level of complement component C3. Recurrences were more frequent in patients >8 years of age (OR 3.7, CI 2.0 to 7.0, p<0.001) and in patients with nephritis (OR 4.6, CI 2.3 to 8.9, p<0.001). Patients with severe HSP nephritis had more extrarenal symptoms up to 6 months. There was no difference in the clinical course between the prednisone-treated and non-treated patients during the 6-month follow-up. Conclusions Serum albumin is often low in HSP patients without proteinuria, due to protein loss via the intestine. Although corticosteroids alleviate the symptoms, they seem not to alter the clinical course of HSP during 6 months of follow-up.

Peritoneal dialysis in children under two years of age

BACKGROUND Although results of peritoneal dialysis (PD) in small children have improved during recent years, the youngest children have poorer growth, more infections and higher mortality than do older children. METHODS In this retrospective study, we analysed patient records of all children under age 2 treated with continuous peritoneal dialysis (CPD) between 1995 and 2000 in Finland. Diagnoses leading to renal failure in these 23 children were congenital nephrotic syndrome of the Finnish type (13), polycystic kidney disease (4), a urethral valve (3), renal insufficiency due to neonatal asphyxia (2) and Prune-Belly syndrome (1). Of these 23, 17 (74%) were anuric. RESULTS The mean age at the onset of PD was 0.4 years and the mean time on dialysis 1.4 years. Hernias were diagnosed in 57%. The peritonitis rate was 1:14.5 patient-months, and 30% were peritonitis-free. Hypertension was common, and 70% had at least one period on antihypertensive medication. None of the patients had pulmonary oedema or dialysis-related seizures. The mean height standard deviation score (hSDS) at the start of PD (n = 16) was -2.0 and after 9 months -1.6. Catch-up growth was documented in 64% of the patients during dialysis. Hospitalization time was 124 days/patient-year. Two patients (9%) died. CONCLUSIONS Our results are reassuring. Mortality was low, laboratory parameters were acceptable and growth was good. Peritonitis rate was comparable to that in older children. Correction of inguinal hernia should be routinely performed; high blood pressure is still a problem.

Hypertension, cardiac state, and the role of volume overload during peritoneal dialysis

Abstract The cardiac state and the prevalence of high blood pressure (BP) were analyzed in 21 pediatric patients (mean age 5.3±5.3 years) on chronic peritoneal dialysis (CPD), the aim being to specify the impact of hypervolemia in the etiology of hypertension. C- and N-terminal atrial natriuretic peptide (ANP-C, ANP-N) were measured as possible additional markers of hypervolemia. Baseline investigations were carried out 0.2 years after initiation of PD, and repeated after 0.9±0.2 years. Fifty-two percent of the patients had high BP, and in 40% the nocturnal BP decline was decreased. Left ventricular hypertrophy was present in 45%, but the systolic and diastolic functions of the heart were not impaired. Left ventricular mass correlated significantly with the severity of hypertension and with ANP-N (r=0.79, P<0.01 and r=0.66, P<0.01, Spearman rank correlation). Significant correlations were also found between the severity of hypertension and ANP-N and ANP-C (r=0.82, P<0.01 and r=0.66, P<0.01, Spearman rank correlation). High BP and cardiac impairment were more frequent in the younger and nephrectomized patients in whom volume overload seemed to be the most-important etiological factor. Our results suggest further that an ANP-N over 3.0 nmol/l combined with hypertension is strongly indicative of volume overload in patients on PD.

Pubertal development is normal in adolescents after renal transplantation in childhood.

Background. This study was conducted to evaluate the pubertal development in adolescents after renal transplantation (RTx) in childhood. Methods. We performed a retrospective review of medical records of 109 RTx recipients (72 males) transplanted at the median age of 4.5 years (range: 0.9–15.8 years). Data on the clinical signs of puberty, growth, bone age, medication, and graft function of 98 patients were analyzed. Furthermore, serum levels of reproductive hormones in 87 patients were assessed to evaluate the progression and outcome of pubertal development. Results. The age at the onset of puberty averaged 12.7 years (range: 9.4–16.2 years) in 55 males and 10.7 years (range: 8.9–12.7 years) in 29 females. The mean age at menarche was 12.5 years (range: 10.5–14.5 years). Twenty-two percent of the boys and none of the girls had a moderately delayed onset of puberty. Children who underwent RTx before the age of 5 years reached puberty earlier than those transplanted at later age (boys 12.3±1.2 vs. 13.4±1.5 years, P<0.01; girls 10.3±0.9 vs. 11.0±1.0 years, P>0.05). The mean length of puberty was 3.9 and 4.7 years for boys and girls, respectively. The bone age was delayed in practically all, and final height was reached at the mean age of 18.1 and 16.0 years in boys and girls, respectively. Pubertal maturation resulted in acceptable final height and reproductive hormone status in great majority of the patients. Conclusion. Pubertal development was normal in all female and most male adolescents after RTx in childhood.

Encapsulating peritoneal sclerosis in children on chronic PD: a survey from the European Paediatric Dialysis Working Group

BACKGROUND Encapsulating peritoneal sclerosis (EPS) is a rare complication of peritoneal dialysis (PD) that is associated with significant morbidity and mortality in adults. There are scarce data for children. We performed a 10-year survey to determine the prevalence, risk factors and outcome for EPS in children. METHODS Chronic PD patients in 14 dialysis units participating in the European Paediatric Dialysis Working Group between January 2001 and December 2010 were included in this study. RESULTS Twenty-two cases of EPS were reported (prevalence 1.5%; 8.7 per 1000 patient-years on PD). Median PD vintage was 5.9 (1.6-10.2) in EPS and 1.7 (0.7-7.7) years in the remainder of the PD population (P<0.0001). EPS patients had a significantly higher peritonitis rate than non-EPS patients (P=0.2). EPS was diagnosed while the child was on PD in 17 (77%), after conversion to haemodialysis (HD) in 3 and after transplantation in 2. Fifteen of 17 (88%) developed ultrafiltration (UF) failure. The median interval between UF failure and presentation with bowel obstruction was 2.8 (0.02-5.8) months. Twenty (91%) had clinical and radiological signs of bowel obstruction. Enterolysis was performed in 14 and 19 received immunosuppression or tamoxifen. Nine required parenteral nutrition. At final follow-up 4.8 (1.3-8.7) years after EPS diagnosis, 3 patients died, 11 had a functioning transplant and 8 were on HD. CONCLUSIONS The prevalence of EPS in European children on PD is comparable with that of adult PD patients, but mortality from paediatric EPS is significantly lower. A high index of suspicion is required for the diagnosis of EPS in children with longer dialysis duration, a high peritonitis rate and UF failure.

Vaccination Practices in Pediatric Dialysis Patients Across Europe. A European Pediatric Dialysis Working Group and European Society for Pediatric Nephrology Dialysis Working Group Study

Background: Data on the immunization practices in pediatric chronic kidney disease (CKD) patients are scarce. The purpose of this study was to evaluate current vaccination practices for children on dialysis across European pediatric nephrology centers. Methods: A total of 18 tertiary pediatric nephrology centers from 12 European countries were included in the study. The data on universal national immunization programs and immunization practices for children with chronic disease or risk were recorded from European Center for Disease Prevention and Control and the World Health Organization. The immunization practices and center protocols for monitoring antibody titers after vaccination in dialysis patients were obtained through a questionnaire. Results: All centers included in the study recommended immunization against hepatitis B virus (HBV), diphtheria, tetanus, pertussis, Hemophilus influenzae type b (Hib), poliomyelitis, measles, mumps, rubella (MMR), and streptococcus pneumonia in dialysis patients. In 16 centers, dialysis patients were vaccinated against influenza virus annually. HBV protective antibody titers were measured in 17 centers (during dialysis period in 14 centers, during pre-renal transplantation preparations in 14 centers or in both times in 11 centers). Hepatitis A virus (HAV) was reported to be followed in 13 centers, in 8 centers during dialysis period, and in 11 centers during pre-RTx preparations. MMR and varicella-zoster virus (VZV) protective antibody titers were measured during the dialysis period or before renal transplantation (RTx) in 12 and 15 centers, respectively, and in 6 centers both titers were checked both times. Conclusion: There are variations in vaccination practice across Europe. Children with CKD, those undergoing dialysis, and transplant candidates should receive age-appropriate vaccinations before RTx as well as before the transition to adult nephrology clinics and antibody levels should be monitored to evaluate the immunization status before and after RTx.

Management of children with congenital nephrotic syndrome: challenging treatment paradigms

Background Management of children with congenital nephrotic syndrome (CNS) is challenging. Bilateral nephrectomies followed by dialysis and transplantation are practiced in most centres, but conservative treatment may also be effective. Methods We conducted a 6-year review across members of the European Society for Paediatric Nephrology Dialysis Working Group to compare management strategies and their outcomes in children with CNS. Results Eighty children (50% male) across 17 tertiary nephrology units in Europe were included (mutations in NPHS1, n = 55; NPHS2, n = 1; WT1, n = 9; others, n = 15). Excluding patients with mutations in WT1, antiproteinuric treatment was given in 42 (59%) with an increase in S-albumin in 70% by median 6 (interquartile range: 3-8) g/L (P < 0.001). Following unilateral nephrectomy, S-albumin increased by 4 (1-8) g/L (P = 0.03) with a reduction in albumin infusion dose by 5 (2-9) g/kg/week (P = 0.02). Median age at bilateral nephrectomies (n = 29) was 9 (7-16) months. Outcomes were compared between two groups of NPHS1 patients: those who underwent bilateral nephrectomies (n = 25) versus those on conservative management (n = 17). The number of septic or thrombotic episodes and growth were comparable between the groups. The response to antiproteinuric treatment, as well as renal and patient survival, was independent of NPHS1 mutation type. At final follow-up (median age 34 months) 20 (80%) children in the nephrectomy group were transplanted and 1 died. In the conservative group, 9 (53%) remained without dialysis, 4 (24%; P < 0.001) were transplanted and 2 died. Conclusion An individualized, stepwise approach with prolonged conservative management may be a reasonable alternative to early bilateral nephrectomies and dialysis in children with CNS and NPHS1 mutations. Further prospective studies are needed to define indications for unilateral nephrectomy.

Peritoneal Dialysis During Infancy

In the early years of renal replacement therapy, there has been doubt if it would be ethically justified to treat end-stage renal disease (ESRD) in newborns and infants with maintenance peritoneal dialysis due to their higher technical complication rates, morbidity, and mortality in comparison to older children [1, 2]. At the end of the 1990s, only 50% of pediatric nephrologists offered dialysis to patients under 1 year of age, and only 40% offered this treatment to neonates [3]. However, during recent years, an increasing number of publications have reported satisfactory outcomes with respect to morbidity, mortality, growth, and development [4–11]. Thus, in experienced centers, results comparable to those achieved in older children can be achieved and most countries with available resources offer treatment to the majority of infants.