Varicella vaccination in children with steroid-sensitive nephrotic syndrome

We have studied serological and clinical response to live, attenuated varicella zoster virus (VZV) vaccine (Varilrix, SmithKline Beecham) in 20 patients with steroid-sensitive nephrotic syndrome (SSNS) in remission and 22 normal controls who had no history of varicella and no detectable antibody to VZV. Nephrotic patients included 15 boys and 5 girls, with a mean age of 4.7 years (range 2–11.4 years). The controls were healthy age-matched children (13 girls and 9 boys). Seventeen patients with SSNS (85%) and 19 healthy controls (86%) seroconverted 8 weeks after vaccination. One patient with SSNS had a relapse 20 days after vaccination, and 1 child in the control group had a rash. Two years after vaccination, antibodies to VZV were detected in 12 of 17 responders, 2 of 3 non-responders, and 13 of 22 controls. Within 2 years of vaccination, 3 of the vaccine responder children with SSNS had a mild varicella infection. Two responder and 1 non-responder nephrotic children and 9 controls were lost to long-term follow-up. Our results show that immunization with a single dose of VZV vaccine is safe and effective in children with SSNS in remission. Received: 9 May 2001 / Revised: 15 November 2001 / Accepted: 18 November 2001     

Immunization in children with chronic renal failure

Infections jeopardize children on immunosuppression after organ transplantation. Immunization is protective in healthy children. The aims of this study were to analyze the rate and efficacy of immunization in 62 children undergoing dialysis and renal transplantation (RTPL) between 1987 and 2000. The analysis was based on clinical findings, vaccination certificates, and measurement of specific serum antibodies. A member of the renal unit administered vaccinations. All 62 patients were immunized against diphtheria, tetanus, pertussis, poliomyelitis, measles, mumps, rubella, and hepatitis B. Since introduction in 1991 and 1995, 44 and 42 children were also vaccinated against influenza and Hemophilus influenzae type b, respectively. Of 16 patients with a negative history, 14 were given varicella vaccine; 16 children on peritoneal dialysis (PD) or with nephrotic syndrome were immunized against Streptococcus pneumoniae. All vaccinated patients had detectable serum antibodies against measles, mumps, rubella, varicella, hepatitis B, H. influenzae, and S. pneumoniae. There were 3 infections despite vaccination; 1 patient developed varicella after RTPL and 1 patient on PD had 2 episodes of peritonitis caused by H. influenzae and S. pneumoniae. In conclusion, monitoring and administration of the vaccines by the renal team enabled a high immunization rate. Whether vaccines, as documented by antibody titers, or by the low prevalence in the general population promoted the low prevalence of infections remains open, as there were at least a few vaccination failures.     

Parathyroidectomy in children with chronic renal failure

Severe bone disease complicates chronic renal failure in children more frequently than in adults. The bony changes of renal origin are regularly reversed by successful renal transplantation. When a renal transplant cannot be accomplished at an early date, this osteodystrophy may become disabling. Under these circumstances bony changes are not arrested by medical therapy and subtotal parathyroidectomy is indicated.     

Aluminum loading in children with chronic renal failure

Plasma aluminum levels were measured in 17 children with chronic renal failure who were receiving aluminum containing antacids for the control of hyperphosphatemia. Seven children were on hemodialysis, five on peritoneal dialysis, and five were awaiting dialysis with creatinine clearances between 10 to 20 cc/min/1.73 m2. Plasma aluminum levels correlated directly with oral aluminum dosage; extremely high levels were documented in small, nondialyzed children. Bone aluminum levels were measured in four children with high plasma levels and confirmed significant aluminum loading. Other factors such as the level of aluminum in dialysate and tap water were measured and were not contributory. All patients with plasma aluminum levels greater than 100 micrograms/liter had signs of aluminum toxicity and were receiving greater than 75 mg/kg/day of elemental aluminum orally. We concluded that children who require greater than 30 mg/kg/day of elemental aluminum to control hyperphosphatemia should have plasma aluminum levels monitored and/or be considered for other forms of therapy including more restricted diets and earlier or more aggressive dialysis.     

Psychiatric disorders in children with chronic renal failure

Psychiatric assessment was done according to the DSM-IV TR criteria in 19 children with predialysis chronic renal failure (CRF) and 19 children with end-stage renal disease on regular hemodialysis. The prevalence rate of psychiatric disorders in all the studied patients was 52.6%. Adjustment disorders were the most common disorders (18.4%), followed by depression (10.3%) and neurocognitive disorders (7.7%). Anxiety and elimination disorders were reported in 5.1 and 2.6%, respectively. The disorders were more prevalent (P=0.05) in dialysis (68.4%) than in predialysis patients (36.8%). The presence of psychiatric disorders was not significantly correlated with sex, severity of anemia, duration of CRF or the efficiency or the duration of hemodialysis. In conclusion, psychiatric disorders were prevalent in our patients, especially in those on hemodialysis. Both adjustments with depression and depressive disorders were the most common psychiatric disorders. This array of disorders was more likely explained by the difficulties encountered in living with CRF rather than by demographic or physical factors.     

Growth in young children with chronic renal failure

Statural growth and its relation to growth potential, renal function, blood urea nitrogen (BUN), mineral metabolism hormones and dietary intake were studied in 17 prepubertal children (aged 1.6–9.3 years) on conservative treatment for chronic renal failure due to tubulo-interstitial nephropathy. Statural growth (height SDS) was related to the degree of renal failure, was more retarded than ossification, and was independent of the chronological age of the patients. We observed that the lower the glomerular filtration rate (GRF), the lower was the growth potential (increased bone age/statural age ratio). Growth velocity may be normal regardless of statural and bone maturation delay and the degree of renal insufficiency. Impaired growth rate correlated with parathyroid hormone levels, caloric intake and increased blood urea nitrogen during the year of observation. These data show that comprehensive monitoring and suitable treatment must be performed in order to prevent growth retardation at any GFR level.     

Electrocardiographic monitoring in children with chronic renal failure

Continuous electrocardiographic (ECG) monitoring was performed over 24 h in 44 children at various stages of chronic renal failure in order to determine the incidence and nature of cardiac dysrhythmias. In addition the ECG was followed during haemodialysis sessions and during dialysate exchanges in continuous ambulatory peritoneal dialysis (CAPD) patients. In contrast to adult patients on haemodialysis life-threatening dysrhythmias were not observed. The proportion of children with premature ventricular complexes (41%) was at the upper limit of that in healthy children. A relatively high heart rate was found in children on CAPD, which varied during the exchange procedure. In 57% of all patients a transient marked prolongation of the QT interval up to 40% greater than normal was observed without obvious changes in the serum electrolyte levels. Continuous ECG monitoring is a useful tool for detecting alterations of cardiac rhythm and conduction in at-risk children with renal failure.     

Oral health in children with chronic renal failure

Seventy children with chronic renal failure (CRF) aged 4-13.6 years were recruited from the Renal Unit of the Great Ormond Street Hospital for Children. Indices were recorded for dental caries, dental plaque, gingival inflammation, gingival enlargement, and enamel defects. Salivary urea, buffering capacity, and the oral streptococcal flora were determined for 25 of the children. A significantly greater proportion of the CRF children was caries free, 40% compared with 8.5% of the controls. The mean plaque score was significantly greater in the CRF group for both the primary 12.7 (16) and permanent dentition 22.0 (18.2) compared with the controls, 5.3 (7.6) and 15.5 (13.3), respectively. Eight CRF children had gingival enlargement. Enamel defects affecting the permanent teeth were observed in 57% of the CRF children compared with 33% of the controls. The buffering capacity was significantly greater in the CRF group, pH 6.4 (0.5) compared with the controls pH 5.6 (0.8). The mean salivary urea level (mmol/l) was significantly greater in the CRF children, 11.6 (5.9) compared with 3.6 (1.4) for the controls. The isolation frequency of Streptococcus mutans was significantly greater from controls compared with the CRF children ( P=0.002). An integrated dental service needs to be developed with emphasis on tooth brushing to prevent gingival hyperplasia and periodontal disease after puberty.     

Endothelin-1 in children with chronic renal failure

Endothelin-1 (ET-1) was meansured after extraction from plasma of normal adults (5.9±1.9 pg/ml,n=22), normal children (7.1±1.86 pg/ml,n=29), nonhaemodialysed children with chronic renal failure (CRF) (11.1±1.8 pg/ml),n=10), renal graft recipients (9.5±3.4 pg/ml,n=37), haemodialysed children 24 h after a haemodialysis session (20.02±10.9 pg/ml,n=26) and haemodialysed children before and after a haemodialysis session (15.31±10.6 and 13.8±8.5 respectively,n=14). A sensitive and specific radioimmunoassay was used. ET-1 was significantly higher in non-haemodialysed CRF children and in renal graft recipients than in normal children (P<0.001 andP<0.01, respectively) and significantly higher in haemodialysed children when compared with normal children, non-haemodialysed CRF children and renal graft recipients (P<0.001). ET-1 concentrations were similar in normal children and normal adults. ET-1 was inversely correlated with glomerular filtration rate in non-haemodialysed CRF children (r=–0.39,P<0.01) and positively correlated with extracellular volume in haemodialysed children (r=0.435,P<0.03). After haemodialysis, ET-1 increased in 6 and decreased in 8 of the 14 children studied before and after a haemodialysis session.     

QTc interval in children with chronic renal failure and with renal transplants

Prolongation of the QTc interval, a risk factor for cardiac arrhythmias, has been observed in adult hemodialysis patients; there are few data on the QTc interval in children with chronic renal failure (CRF) and following renal transplantation (Tx). The purpose of our study was to determine the QTc interval in children with CRF and post renal Tx. Twenty children with CRF and 16 children with renal Tx who were followed at the University of California, Davis, underwent prospective EKG monitoring. The mean QTc interval in the CRF and post-Tx cohorts was normal at 407.9 ms and 408.2 ms, respectively. None of the children with CRF had QTc prolongation. Two Tx recipients had QTc prolongation; both had cardiac dilatation on echocardiography (ECHO). There was no correlation between the QTc interval and the creatinine clearance in either group. However, a significant correlation was noted between QTc prolongation and cardiac dilatation on ECHO in the Tx group (P=0.02, Fisher’s exact test). In conclusion, QTc prolongation is uncommon in children with CRF and following Tx, in the absence of cardiac dilatation. However, caution is still needed before prescribing medications known to cause QTc prolongation. Received: 7 March 2001 / Revised: 17 July 2001 / Accepted: 23 July 2001     

Growth in children with chronic renal failure and after renal transplantation

Growth retardation is a major problem for many children with chronic renal failure (CRF) and transplantation. The aim of this study is to assess the relation between height, glomerular filtration rate (GFR), hormonal alterations in children with CRF on regular haemodialysis (HD), and the impact of functioning graft after kidney transplantation. Thirty-six hemodialysed children were included in the study beside 32 pediatric transplants. Mean duration on HD was 14.72 ± 7.73 months for the CRF group, while the mean interval after transplantation was 1.97 ± 0.9 years for the second group. Moreover, twenty healthy children of matched age and sex served as controls. Assessment of growth parameters included height, expressed as standard deviation scores (Ht SDS) for chronological age, serum levels of growth hormone (hGH), and parathormone (PTH). Growth performance was evaluated twice: at the start of the study and one year later. Children with CRF and transplantation had significantly higher levels of both serum hGH and PTH compared to their controls, while CRF children experienced significantly higher serum levels of both hGH and PTH compared to those with functioning graft. Furthermore, analysis of our results by non-parametric Kendall’s correlation at the start and one year later revealed negative correlation concerning dialysis duration, serum creatinine, and PTH. On the other hand, positive correlation was achieved for serum calcium and GFR.     

Plasma homocysteine concentration in children with chronic renal failure

Hyperhomocysteinemia, a risk factor for vascular disease, is commonly found in adult patients with end-stage renal disease. Major determinants of elevated plasma homocysteine levels in these patients include deficiencies in folate and vitamin B₁₂, methylenetetrahydrofolate reductase (MTHFR) genotype and renal function. Little information is available for children with chronic renal failure (CRF). The prevalence and the factors that affect plasma homocysteine concentration were determined in children. Twenty-nine children with various degrees of CRF (15 were dialyzed, 14 were not dialyzed) were compared with 57 age- and sex-matched healthy children. Homocysteine concentrations were higher in patients than controls (17.3 μmol/l vs 6.8 μmol/l, P<0.0001) and hyperhomocysteinemia (>95th percentile for controls: 14.0 μmol/l) was seen in 62.0% of patients and 5.2% of controls. Folate concentrations were lower in patients (9.9 nmol/l) than controls (13.5 nmol/l), P<0.01. Vitamin B₁₂ was similar in patients (322 pmol/l) and controls (284 pmol/l). Dialyzed patients have a higher prevalence of hyperhomocysteinemia than nondialyzed patients (87% vs 35%). Dialyzed patients with MTHFR mutation have higher plasma homocysteine (28.5 μmol/l) than nondialyzed patients with the mutation (10.7 μmol/l), P<0.002. In our study, differences between controls and patients in plasma homocysteine concentrations are observed when age is greater then 92 months, folate less than 21.6 nmol/l and vitamin B₁₂ less than 522 pmol/l.Our study shows that hyperhomocysteinemia is common in children with CRF and is associated with low folate and normal vitamin B₁₂ status, compared to normal children. Among the patients, the dialyzed patients with the MTHFR mutation are particularly at risk for hyperhomocysteinemia. Further studies are needed to investigate therapeutic interventions and the potential link with vascular complications in these patients. Received: 26 January 2001 / Revised: 16 April 2001 / Accepted: 17 April 2001     

Connective tissue metabolism in children with chronic renal failure

To assess the characteristics of connective tissue metabolism in chronic renal failure (CRF), urinary excretion of glycosaminoglycan (GAG) fractions and hydroxyproline (HYP) was determined in ten patients with CRF and in ten age-matched healthy children. CRF was found to be associated with elevated free HYP (19.9±6.1 vs 9.8±3.6 mol/day,P<0.05) and depressed peptide HYP excretion (33.1±13.5 vs 225.2±17.7 mol/day,P<0.01), a low rate of total GAG excretion (7.0±2.4 vs 16.1±1.9 mol uronic acid/day,P<0.05) with low chondroitin 4 — sulphate + chondroitin 6 — sulphate (Ch-Ss) (14.0±9.9 vs 65.0±22.1%) and a high proportion of non-sulphated or under-sulphated fractions, i.e. hyaluronic acid + chondroitin + heparan sulphate (HA+Ch+HS) (75.3±11.4 vs 31.5±5.7%). Urinary 3-methyl-histidine (3-met-HIS) excretion and plasma essential free amino acids did not differ in the two groups. In response to haemodialysis no consistent change occurred in urinary excretion of 3-met-HIS, peptide-bound HYP, total GAG or percentage distribution of individual GAG fractions. After haemodialysis all plasma amino acids decreased significantly, and there was a significant increase in urinary excretion of free HYP (P<0.05). We conclude that the alterations in urinary excretion of total and individual GAGs observed in CRF may reflect disturbed connective tissue metabolism which does not appear to be accounted for by protein malnutrition or enhanced protein breakdown and remains uninfluenced by haemodialysis therapy.     

Growth retardation in children with chronic renal failure.

Growth retardation is a major obstacle to full rehabilitation of children with chronic renal failure (CRF). Several factors have been identified as contributors to impaired linear growth and they include protein and calorie malnutrition, metabolic acidosis, growth hormone resistance, anemia, and renal osteodystrophy. Although therapeutic interventions such as the use of recombinant human growth hormone, recombinant human erythropoietin, and calcitriol have made substantial contributions, the optimal therapeutic strategy remains to be defined. Indeed, growth failure persists in a substantial proportion of children with renal failure and those treated with maintenance dialysis. In addition, the increasing prevalence of adynamic lesions of renal osteodystrophy and its effect on growth have raised concern about the continued generalized use of calcitriol in children with CRF. Recent studies have shown the critical roles of parathyroid hormone-related protein (PTHrP) and the PTH/PTHrP receptor in the regulation of endochondral bone formation. The PTH/PTHrP receptor mRNA expression has been shown to be down-regulated in kidney and growth plate cartilage of animals with renal failure. Differences in the severity of secondary hyperparathyroidism influence not only growth plate morphology but also the expression of selected markers of chondrocyte proliferation and differentiation in these animals. Such findings suggest potential molecular mechanisms by which cartilage and bone development may be disrupted in children with CRF, thereby contributing to diminished linear growth.     

Bone alkaline phosphatase in children with chronic renal failure

Background: With the introduction of a new immunoradiometric assay based on two monoclonal antibodies (Tandem®-Ostase, Hybritech) the determination of bone alkaline phosphatase (BAP) to evaluate bone metabolism in chronic renal failure has become easier and more valid. Subjects and methods: Using this test we investigated BAP in a total of 90 paediatric patients, 42 (9.2±5.5 years) with chronic renal failure on conservative treatment, 22 (9.5±5.4 years) under chronic dialysis, and 26 (16.2±5.9 years) after renal transplantation, compared to 203 controls (10.1±5.7 years). Results: The physiological age dependency found in controls including two peaks during infancy and puberty was distinctly disturbed in chronic renal failure. However, in patients BAP significantly correlated with height velocity rather reflecting the last 6 (r=0.56 P<0.001) than the last 12 months. Although BAP correlated well with total alkaline phosphatase (TAP; r=0.95 P<0.001), a significant correlation with the serum level of the intact parathyroid hormone could only be detected for BAP (r=0.45 P<0.001) but not for TAP (R=0.19 N.S.) Furthermore, BAP positively correlated with trabecular (n=40; r=0.40 P<0.05) and inversely with cortical bone density (n=19; r=-0.58 P<0.01) but no relationship was found with conventional X-ray. Conclusion: BAP determined by the new radioimmunoassay seems to represent an additional diagnostic tool to assess growth and bone turnover in paediatric patients with chronic renal failure that is complementary to the information provided by X-ray and total alkaline phosphatase. Key words: bone alkaline phosphatase; children; chronic renal failure      

Nutritional management of children with chronic renal failure

Current information on the adaptations to progressive loss of renal function is presented. The assessment of renal function in infants and children using serum creatinine concentration and its derivatives is considered as are various methods for assessment of growth. Children with creatinine clearances less than 50% of normal, who do not have uremic symptoms (and who are not on dialysis), should be ingesting diets providing close to 100% of the RDA for calories with 8% of the calories as protein. Recommendations for nutritional management of children on chronic peritoneal dialysis are also presented.