Problems in interhospital pediatric intensive care transport in The Netherlands: results from a survey of general pediatricians.

OBJECTIVE: Interhospital pediatric intensive care transport accompanied by non-trained specialists usually occurs with inadequate equipment and has been associated with high incidence of complications. These facts have serious consequences for patients but also can be very disconcerting for specialists. This survey was undertaken to gain insight into the problems encountered in organizing pediatric intensive care transport in The Netherlands to measure the specialist's satisfaction or dissatisfaction with the current state of affairs in the organization of such transports, and additional workload and feelings of insecurity experienced during self-organized transports. DESIGN: Survey, retrospective. SETTING: A postal questionnaire sent to all pediatricians of community hospitals in The Netherlands. METHODS: Results of direct questioning are given as discrete frequencies. After factor and reliability analysis 5-point Likert scale items are summed up in scale constructions. Relationships between scales are examined in regression analysis. RESULTS: Pediatricians appear to be satisfied with current specialist retrieval teams if these teams are available in their region, and highly dissatisfied if not available. Many nontrained specialists consider these transports burdening tasks with a high workload, and they feel insecure during these transports, especially if they report lack of knowledge of the transport equipment. CONCLUSIONS: The need for pediatric specialist retrieval teams in The Netherlands is seen not only in the insufficient level of care delivered by accompanying nontrained specialists and the reported high incidence of complications as shown in the literature but also in the dissatisfaction and high stress of these specialists.

Distal nephron sodium-potassium exchange in children with nephrotic syndrome.

While recent literature data suggest that a primary impairment in sodium excretion is the basic abnormality in the pathogenesis of edema formation in the nephrotic syndrome, there is ample evidence that functional hypovolemia contributes to stimulation of renal sodium and fluid retention. Vasoactive hormones such as renin and aldosterone are involved in this process. Discrimination between both mechanisms would be possible by assessment of aldosterone bioactivity and will have therapeutical consequences by indicating the need for administration of i.v. albumin or diuretics. In this paper, several indices of aldosterone bioactivity were assessed in 85 patients with minimal lesion nephrotic syndrome (118 measurements were performed in patients while in remission and 210 following relapses), and in 41 nephrotic patients with different types of nephropathy and were related to plasma renin and aldosterone levels. A better correlation was found between log aldosterone and U(K+)/U(Na+) + U(K+) ratio than with other parameters measuring renal potassium handling such as transtubular potassium gradient, fractional excretion of potassium and urine K+/urine Na+ or urine K+ creatinine ratios. In patients with renal sodium retention (FE(Na)% less than 0.5), an U(K+)/U(Na+) + U(K+) ratio higher than 0.60 identifies patients with increased aldosterone levels and indicates functional hypovolemia. This index may therefore be used to assess which patients will benefit from i.v. albumin administration.

[Transfer of the care for adolescents with chronic illnesses: from pediatrics to specialists for adults]. / Overdracht van de zorg voor adolescenten met chronische ziekten: van kindergeneeskunde naar specialismen voor volwassenen.

Over the past few decades, paediatrics has increasingly been characterised by many developments in medical technology. This has led to a dramatic change in the clinical outcome of many severe and chronic childhood diseases. The number of children dying due to a severe illness has decreased, and at the same time the number of children surviving with a chronic disease or handicap has increased. This development requires that paediatricians and physicians in adult care adopt new initiatives so as to ensure an efficient and caring transfer of adolescents from paediatric to adult care. The purpose of this transition is (a) preparing the patient for the transfer to adult medicine by gaining an understanding of the clinical picture and the treatment goal and possibilities, and obtaining a personal responsibility for medication and diet and (b) tuning paediatric care and adult care to one another. Procedures for the transition should be established in a protocol. The responsibility for monitoring the process lies in principle with the treating paediatrician.

Pathogenesis of edema formation in the nephrotic syndrome.

Based on observations in 110 children with nephrotic syndrome (NS) and data from the literature, existing concepts on the pathogenesis of edema formation in the NS have been modified. The data suggest that the basic abnormality is a primary disturbance in renal sodium excretion. Depending on the stage in the development of the NS, the rate of progression in the development of hypoproteinemia, and the absolute levels of plasma oncotic pressure, functional hypovolemia may develop, resulting in stimulation of hemostatic mechanisms and secondary sodium retention. This applies as much to patients with minimal change NS as to patients with histological lesions. Alterations in kidney function (glomerular filtration rate, renal plasma flow, filtration fraction) in the NS cannot be explained by hypo- or hypervolemia, but reflect variations in plasma oncotic pressure and glomerular basement membrane permeability. These abnormalities will also influence sodium excretion. Evaluation of the presence of functional hypovolemia will have therapeutic consequences. A quick diagnosis can be made by assessment of FENa+ and UK+/ (UK+ + UNa+) Sodium retention associated with increased distal Na/K exchange indicates functional hypovolemia, and may be treated by albumin infusion if clinically required.

Pathophysiology of edema formation in children with nephrotic syndrome not due to minimal change disease.

It has been shown that children with nephrotic syndrome due to minimal change disease (MCD) can present with avid salt retention and stimulated vasoactive hormones, as well as with stable edema. The present study examines these conditions in children with nephrotic syndrome not due to MCD (non-MCD). In six children with hypovolemic symptoms (congenital nephrotic syndrome in four), strong sodium retention (fractional sodium excretion, FE(Na), 0.2 +/- 0.2%) was found. Lithium clearance (FE(Li)) and maximal water excretion (Vmax) were suppressed, suggesting avid sodium reabsorption throughout the nephron. Aldosterone, renin, and norepinephrine were elevated. Sixteen other children with non-MCD had stable edema. FE(Na) was 1.8 +/- 1.1%, whereas FE(Li), Vmax, and hormones were normal, and not different from data in 35 nonproteinuric children. In children with MCD, 12 presented with hypovolemic symptoms and strong sodium retention (FE(Na) 0.3 +/- 0.3%), whereas 15 were stable (FE(Na) 1.1 +/- 0.7%). Regarding tubular sodium handling and hormones, the same distinction could be made as for the children with non-MCD. However, hypoproteinemia differed. In the children with non-MCD lesions, plasma colloid osmotic pressure was significantly lower in the hypovolemic types (4.2 +/- 0.4 mmHg) than in those with stable edema (13.0 +/- 3.8 mmHg; P < 0.05); in MCD, no such difference existed (respectively, 8.1 +/- 3.0 and 9.9 +/- 2.2 mmHg). In summary, children with nephrotic syndrome may present with pathophysiologic pictures of decreased effective circulating volume or of stable edema, regardless of whether they have non-MCD or MCD. The pathogenesis of the hypovolemic picture seems to be different, since it is associated with extreme hypoproteinemia only in the children with non-MCD.

Renal sodium handling in children with nephrotic relapse: relation to hypovolaemic symptoms.

We studied renal sodium handling during water diuresis in children in the early phase of relapse of minimal lesion nephrotic syndrome (MLNS). Findings were related to presence or absence of symptoms suggestive of hypovolaemia, and to neurohumoral factors, and were compared to results of similar studies in the same children in remission. Nine children (aged 7.8 +/- 3.1 years) presented with hypovolaemic symptoms, and 10 (7.4 +/- 4.3 years) without such symptoms. Both groups displayed severe proteinuria, hypoproteinaemia and oedema. Symptomatic patients showed tendency for a low glomerular filtration rate, and significantly impaired urine dilution, decreased fractional sodium and lithium excretions, and elevated diluting segment reabsorption [CH2O/(CH2O + CNa)] and sodium/potassium exchange [UK/(UK + UNa)]. In the non-symptomatic patients these parameters were normal. Plasma renin and aldosterone were significantly elevated in the symptomatic children, and strongly correlated with all parameters of tubule sodium reabsorption. Weaker associations were found for plasma noradrenaline and atrial natriuretic peptide. Vasopressin was also relatively high in the symptomatic group, but showed no association with impaired urine dilution. The diffusely stimulated tubular sodium reabsorption in the symptomatic children, in association with stimulated neurohumoral factors, indicates that secondary sodium retention contributes to oedema formation in at least a subset of children developing a nephrotic relapse. This may be limited to the early stage, and be more pronounced in some patients than in others. The tubular defect responsible for maintenance of oedema in stabilized MLNS remains unclear.

Use of recombinant human growth hormone (rhGH) in pubertal patients with CRI/dialysis/post-transplant: Dutch data. Dutch Study Group on Growth in Children with Chronic Renal Disease.

In the intermediate term, recombinant human growth hormone (rhGH) therapy in a dose of 28-30 i.u./m2/week accelerates growth significantly in most pubertal patients with growth retardation secondary to chronic renal insufficiency (CRI), dialysis and after renal transplantation (RTx), without evidence of adverse effects or acceleration of bone maturation. Therefore, rhGH therapy may well improve the final height of these patients.

[Henoch-Schoenlein purpura-nephritis followed by IgA-nephritis in 3 children]. / Henoch-Schönlein-purpura-nefritis gevolgd door IgA-nefropathie bij drie kinderen.

In three patients, two boys of 7 and 10 and a girl of 9 years old, a kidney disease was diagnosed which evolved from Schönlein-Henoch nephritis to IgA nephropathy or Berger's disease. These two kidney diseases show striking similarities in pathological and immunological respects. Several patients have been described in the literature who suffered from both clinical pictures consecutively and of families in which different members showed either one or the other disease. A remarkable finding was the persistence of an elevated IgA serum level in all three children after the Schönlein-Henoch nephritis had subsided. These cases show the importance of long-term follow up of patients who had Schönlein-Henoch nephritis, in order to diagnose late renal complications at an early stage. They also give more evidence in favour of the assumption that Schönlein-Henoch nephritis and IgA nephropathy have a common aetiology.

A placebo-controlled, double-blind trial of growth hormone treatment in prepubertal children after renal transplant.

Sustained growth retardation in spite of a successful renal transplantation (RTx) is a serious problem for many pediatric allograft recipients. Biosynthetic growth hormone (GH) was given to 11 prepubertal children with severe growth retardation after RTx in a placebo-controlled double-blind study, assessing its effect on height velocity (HV), bone maturation, renal function, plasma IGF-I and IGF-II, serum IGF-binding proteins (IGFBP), and lipid and carbohydrate metabolism. Six months of GH (4 IU/m2/day s.c.) was either preceded or followed by six months of placebo. The patients underwent a full examination every three months. All children completed the study. Mean HV improved significantly with GH therapy (P < 0.0001), but there was also some improvement with placebo (P = 0.06). The GH-induced HV increment exceeded that of placebo by 2.9 cm/six months. Bone maturation was not accelerated. Acute renal graft rejection did not occur in any of the patients. 125I-thalamate and 131I-hippuran tests showed that mean glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) did not change significantly during GH therapy. GH caused a significant increase in IGF-I (P < 0.0001), which was far greater than the insignificant increase in serum IGFBP-3 levels (P = 0.16). Mean serum levels of total cholesterol, low density lipoprotein, apolipoprotein-A1 and -B, which are elevated at the start of the study compared with that of controls, did not change significantly during GH therapy. GH induced a significant increase in mean integrated plasma insulin levels during oral glucose tolerance test, without changing plasma glucose levels. Serum fructosamine and parathyroid hormone levels remained constant. Impressive HV increment can be achieved with GH therapy in children with growth retardation after RTx, without significant changes in renal function. Bone maturation appears unaffected, suggesting an improve final height.

Volume regulation in children with early relapse of minimal-change nephrosis with or without hypovolaemic symptoms.

The cause of sodium retention in nephrotic syndrome is unclear. Hypovolaemia has traditionally been labelled as the cause but there is evidence in adults of a renal disturbance as the main cause. We aimed to find out whether children with early nephrosis can be classified as hypovolaemic by objective measures. We measured blood volume, kidney function, and hormone concentrations in children with early relapse of minimal-change nephrosis. Three presentations could be defined. The first was patients with incipient proteinuria and normal plasma protein, characterised by sodium retention, increased renal plasma flow, and slightly increased aldosterone, but normal noradrenaline. The second was patients with severe proteinuria, hypoproteinaemia, and hypovolaemic symptoms, who had oedema, sodium retention, and high concentrations of plasma renin, aldosterone, and noradrenaline, low atrial natriuretic peptide, and low glomerular filtration rate. The third was patients with equally severe proteinuria and hypoproteinaemia, but without hypovolaemic symptoms; they had oedema, but no active sodium retention, and normal plasma hormones and glomerular filtration. Neither blood pressure nor blood volume discriminated patients with or without hypovolaemic symptoms. These findings show that children with early full-blown nephrosis can present both with and without hypovolaemic symptoms and laboratory signs, despite equally severe hypoproteinaemia, and also that sodium retention precedes the reduction in serum protein.

Pulmonary hemosiderosis and immune complex glomerulonephritis.

Two children with a syndrome of pulmonary hemorrhage and immune complex nephritis are reported. Clinical history suggests that pulmonary lesions precede renal abnormalities. Necrotizing glomerulonephritis with granular immune deposits along the glomerular basement membrane was found. Although the etiology of this disease complex is still unknown, the clinical and pathological findings in these patients suggest that immune complex glomerulonephritis is an unusual complication of idiopathic pulmonary hemosiderosis.

Amino acid and carnitine supplementation in haemodialysed children.

Plasma carnitine, amino acids and lipids levels were studied in ten uraemic children treated with haemodialysis and given amino acid supplementation with and without carnitine. As carnitine is synthesised from lysine and methionine and has a significant influence on lipid metabolism, the relationship between these was examined. Amino acid supplementation (0.25 g/kg body weight) was started with the intention of improving the plasma amino acid pattern in these children and increasing the concentration of lysine, which is the substrate for carnitine synthesis. Amino acids were administered i.v. during dialysis and carnitine (25 mg/kg body weight i.v.) was administered after dialysis three times a week. Concentrations of most essential amino acids were decreased in these patients. The first period of amino acid supplementation did not increase plasma levels of the essential amino acids, with the exception of tyrosine (P < 0.01). After the second period of supplementation, methionine was increased (P < 0.01), isoleucine was decreased (P < 0.01), but tyrosine normalised and was significantly lower than after the first period (P < 0.05). Thus overall amino acid supplementation did not improve amino acid levels; it was inconsistently associated with a further decrease in high-density lipoprotein-cholesterol and an increase in total protein levels. Lysine concentrations after amino acid supplementation remained low. Paradoxically, before carnitine supplementation a positive correlation between free carnitine and triglycerides was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Rate-dependent distal renal tubular acidosis and carnitine palmitoyltransferase I deficiency.

An infant girl presented with recurrent episodes of Reye-like syndrome associated with hypoketosis and plasma carnitine levels in the high-normal range. A liver biopsy revealed massive macrovesicular steatosis. Ketogenesis was absent after a long-chain triglyceride loading test; in contrast, the medium-chain triglyceride loading test resulted in a brisk rise in plasma ketone concentration. Carnitine palmitoyltransferase I deficiency was demonstrated in cultured skin fibroblasts. Hypoglycemia was only found once in the neonatal period. Renal carnitine handling was normal except for a higher renal threshold for free carnitine. Mild, persistent metabolic acidosis was a constant feature, even during periods between metabolic decompensation. Evaluation of the renal acidification capacity showed a failure to acidify the urine during spontaneous acidosis but increased acid excretion and a normal decrease of urinary pH after acid loading. Also, a small difference between urine and blood PCO2 was found after bicarbonate administration. This acidification defect can best be explained as an abnormality in distal tubular H+ secretion: a rate-dependent distal tubular acidosis.off is speculated that long-chain acylcarnitines, substances that cannot be formed by carnitine palmitoyltransferase I-deficient patients, play an essential role in renal acid-base homeostasis.

Double blind trial comparing the effects of two doses of growth hormone in prepubertal patients with chronic renal insufficiency.

Growth retardation is a major problem for children with chronic renal insufficiency (CRI). Recent studies have convincingly shown that recombinant human GH accelerates growth significantly, but the optimal GH dose with regard to long term growth response and safety has not yet been established. GH therapy was given to 23 prepubertal children (18 boys and 5 girls; mean +/- SD age, 7.1 +/- 3.6 yr; range, 1.6-14.1) with CRI and severe growth retardation in a double blind, dose-response trial. Patients were randomly assigned to either 2 or 4 IU GH/m2.day for 2.5 yr. During the first 6 months, there were comparable and significant increases in height velocity SD score for chronological age with both doses (P < 0.001). However, during the ensuing 2 yr, the higher GH dose induced a significantly greater improvement in height velocity SD score for chronological age than 2 IU GH. Catch-up growth was only sustained for 2.5 yr with 4 IU. In contrast, catch-up growth ceased after 6 months with 2 IU. Neither 2 nor 4 IU GH resulted in accelerated bone maturation during 2.5 yr of therapy. There was a significant increase in plasma insulin-like growth factor-I (IGF-I) levels with either dose, but significantly more so with 4 IU. Plasma IGF-II levels only increased significantly with 4 IU. The pretreatment elevation of IGF-binding protein-1 (IGFBP-1) levels decreased by 50% during the first study year with the higher GH dose, whereas there was no decrease with 2 IU. The elevated pretreatment IGFBP-3 levels increased comparably and significantly with either GH dose. Interestingly, only 4 IU resulted in a significantly greater increase in IGF-I than in IGFBP-3 levels. Regardless of GH dose, there was an insignificant decrease in fructosamine levels, whereas lipid and parathyroid concentrations remained constant. Renal function deterioration did not accelerate. GH therapy with 4 IU/m2.day induced and maintained catch-up growth during 2.5 yr in children with CRI without evidence of adverse effects. Bone maturation did not accelerate. This suggests that this higher GH dose may be beneficial for children with severe growth retardation secondary to CRI.

Final height and its predictive factors after renal transplantation in childhood.

A retrospective study is reported assessing final height (FH) and its predictive factors in 52 patients (31 male, 21 female) who underwent renal transplantation (RTx) before the age of 15 y. They received prednisone daily or on alternate days as well as azathioprine. The study period covered 20 y. FH remained below the third height percentile [height standard deviation score for chronologic age (hSDSCA) < -1.88] for most of these patients (77% males, 71% females). Median (range) FH was 165.0 (143.0-176.8) cm in males and 153.0 (135.0-168.4) cm in females. Median difference between FH and target height was 15.0 and 15.4 cm for males and females, respectively. For both sexes, the median hSDSCA was already below -1.88 at the start of the first hemodialysis, after which it decreased significantly until the first RTx. After RTx, there was no significant improvement of hSDSCA. The predictive factors for FH were determined by evaluating various factors simultaneous in a multiple regression analysis. This analysis provided a regression equation for predicting FH. A higher hSDSCA at the time of the first RTx and alternate-day versus daily prednisone therapy both had a significantly positive influence on FH, whereas a longer duration of reduced GFR (< 50 mL/min/1.73 m2) had a significantly negative effect on FH. Other factors such as age or bone age at first RTx, primary renal disease, duration of initial dialysis, repeat RTx, and the cumulative dose of prednisone did not influence FH significantly. In conclusion, 71-77% of patients that received their first renal transplant before the age of 15 ended up with severely short adult stature. Optimization of the hSDSCA at first RTx appears very important. Long-term administration of prednisone on alternate days would then result in optimal FH, particularly if the GFR remains above 50 mL/min/1.73 m2.

Growth hormone treatment in growth-retarded adolescents after renal transplant.

Growth failure is a psychosocial problem for many patients who have undergone renal transplantation. 18 adolescents (mean age 15.6, range 11.3-19.5) with severe growth retardation after renal transplantation were treated with biosynthetic growth hormone (GH) for 2 years. All received prednisone, administered daily or on alternate days, with azathioprine and/or cyclosporin A. 16 were blindly assigned to one of two GH doses (4 vs 8 IU per m2 per day). Growth, bone maturation, renal graft function, plasma insulin-like growth factors, serum binding proteins, and other biochemical parameters were checked regularly. Glomerular filtration rate and effective renal plasma flow were tested with 125I-Thalamate and 131I-Hippuran. Data on growth and glomerular filtration rate during GH treatment were also compared with those of matched non-GH-treated controls. Mean (standard deviation) increment in height after 2 years of GH was 15.7 (5.1) cm, significantly greater (p < 0.0001) than in matched controls, 5.8 (3.4) cm. Results were similar for the two GH dosage groups. Bone maturation was not accelerated. Glomerular filtration rate and effective renal plasma flow did not change significantly. The incidence of a > 25% reduction in glomerular filtration rate over 2 years was not significantly higher in GH-treated patients than in non-GH-treated controls (39% vs 32%, p = 0.97). Although a few patients had deterioration of graft function, we could not find a relation with GH treatment. Our results show that sustained improvement of height can be achieved with GH in severely growth-retarded adolescents after renal transplantation.