Circadian Rhythm of Glomerular Filtration and Solute Handling Related to Nocturnal Enuresis.

PURPOSE: Although nocturnal polyuria in patients with monosymptomatic enuresis can largely be explained by the decreased nocturnal vasopressin secretion hypothesis, other circadian rhythms in the kidney also seem to have a role. We recently documented an absent day/night rhythm in a subgroup of desmopressin refractory cases. We explore the importance of abnormal circadian rhythm of glomerular filtration and tubular (sodium, potassium) parameters in patients with monosymptomatic enuresis. MATERIALS AND METHODS: In this retrospective study of a tertiary enuresis population we collected data subsequent to a standardized screening (International Children's Continence Society questionnaire), 14-day diary for nocturnal enuresis and diuresis, and 24-hour concentration profile. The study population consisted of 139 children with nocturnal enuresis who were 5 years or older. Children with nonmonosymptomatic nocturnal enuresis were used as controls. RESULTS: There was a maintained circadian rhythm of glomerular filtration, sodium, osmotic excretion and diuresis rate in children with monosymptomatic and nonmonosymptomatic nocturnal enuresis, and there was no difference between the 2 groups. Secondary analysis revealed that in patients with nocturnal polyuria (with monosymptomatic or nonmonosymptomatic nocturnal enuresis) circadian rhythm of glomerular filtration, sodium and osmotic excretion, and diuresis rate was diminished in contrast to those without nocturnal polyuria (p <0.001). CONCLUSIONS: Circadian rhythm of the kidney does not differ between patients with nonmonosymptomatic and monosymptomatic enuresis. However, the subgroup with enuresis and nocturnal polyuria has a diminished circadian rhythm of nocturnal diuresis, sodium excretion and glomerular filtration in contrast to children without nocturnal polyuria. This observation cannot be explained by the vasopressin theory alone.

Sleep fragmentation and increased periodic limb movements are more common in children with nocturnal enuresis.

AIM: To determine sleep fragmentation in children with nocturnal enuresis (NE). METHODS: Paediatricians assessed NE parameters in children referred to an enuresis clinic. Control subjects, matched by age and gender and without incontinence or (un)treated NE, were recruited from the paediatric sleep clinic regardless of their sleep problem. Sleep was investigated by one overnight video-polysomnography in both groups. RESULTS: The study group comprised 67 children with proven NE (50 boys and 17 girls between six and 16 years: 11.1 ± 2.8 SD). They were matched with 67 control subjects (47 boys and 20 girls aged between six and 16 years: 11.0 ± 2.9 SD). Children with NE had a higher incidence of periodic limb movements associated with cortical arousals in their sleep. They displayed significant higher periodic limb movement index, arousal index and awakening index than the control group. CONCLUSION: Children with NE displayed higher sleep fragmentation and periodic limb movements in sleep than the control children with a possible sleep disorder without NE. The findings emphasise the central involvement of the pathophysiology of NE and the multifactorial nature of the condition.

The development of the Belgian paediatric clinical trial network.

Paediatric clinical trials are critical to ensure that medications prescribed to children are safe and effective. However, evidence-based dosing and labelling of such medications remain limited, and most clinical trials in paediatrics fail. Factors for lack of trial completion include performance at site level (limited patient recruitment, limited site staff experience and lack of infrastructure), the sponsor team (limited paediatric specific expertise in design, uncertainties on robustness of biomarkers or outcome variables) as well as regulatory and administrative burdens. As a result of the growing demand for site support, the Belgian Paediatric Clinical Research Network (BPCRN) established in 2009 has been relaunched in 2018 to improve paediatric clinical trials, with the support of innovative-medicines-initiative 2 (IMI2) pan-European network conect4children (c4c) and the transatlantic network I-ACT for Children (US).This paper highlights the formation of the BPCRN and the practical insights it offers for advancing paediatric clinical trials through national networks. A national network can improve trial quality, safety and efficiency, provide clinical research expertise, identify suitable sites, and help with troubleshooting of common trial issues. The BPCRN's centralized approach has advanced paediatric clinical trials by streamlining communication and standardizing trial conduct. Challenges and opportunities have arisen, including a relaunch in 2018, orphan medicine trials, and network sustainability. Collaboration between network activities, government support, site-level improvements, efficient communication, and interaction with industry are key to achieve lasting transformation in paediatric medicine research.

Voiding camp: A successful and unique bladder rehabilitation program for children with urinary incontinence.

INTRODUCTION & BACKGROUND: Standard urotherapy is a well-established treatment for children with incontinence, although it is often challenging for both child and parents, and not always successful. As an alternative, several in- and outpatient bladder training programs have shown positive results on achieving continence. However, the disadvantage is the hospital environment, which can be more stressful for the child, and also quite expensive for society. OBJECTIVE: The aim was to evaluate the outcome on achieving continence following a voiding camp, where standard urotherapy was applied during a one-week stay at a regular summer youth camp, outside the hospital. STUDY DESIGN: Retrospective analysis of 105 children with urinary incontinence, followed in an expert centre for urinary incontinence for at least one year. Data at 7 different time points, before, during and until 6 months after voiding camp were collected. RESULTS: Even though all children had regular follow-up in an expert centre for urinary incontinence for at least one year before participating voiding camp, only 15% of the children reached the recommended amount of daily fluid intake (1.5 L/day). Once minimal daily fluid intake was re-established during the voiding camp, an immediate increase in the maximum voided volume (MVV), and a decrease in the number of wet days and wet nights per week was noted. This effect on a higher MVV remained even 3 months after voiding camp. DISCUSSION: Although sufficient daily fluid intake is a well-established part of standard urotherapy, up until now there was no data that proved the positive impact of sufficient daily fluid intake on bladder volume training and achieving continence in children. CONCLUSION: Voiding camp, as an unique bladder rehabilitation program for children with incontinence, is a successful alternative treatment option. Optimizing the daily fluid intake during voiding camp had a major positive impact on bladder volume training and achieving continence in children.

Oral lyophylizate formulation of desmopressin: superior pharmacodynamics compared to tablet due to low food interaction.

PURPOSE: Desmopressin is a standard treatment for monosymptomatic nocturnal enuresis. Different formulations are promoted as bioequivalent, although these claims are not supported by comparative pharmacodynamic data in children. Food interaction is known to influence the bioavailability of desmopressin. We compared the pharmacodynamics of the 2 most frequently used desmopressin formulations, tablet and lyophilizate, with a standardized meal, allowing extrapolation to clinical reality, where the interval between evening meal and medication intake is limited for school-age children. We hypothesized there would be a faster pharmacodynamic response, and greater concentrating and antidiuretic activity for the fast dissolving (melt) formulation compared to the tablet with simultaneous food intake. MATERIALS AND METHODS: Two tests were performed on separate days in identical standardized conditions, starting with a 15 ml/kg water load. After achieving maximal diluting capacity a standardized meal was administered, followed by desmopressin tablet (t test) or melt (M-test). Diuresis rate and urinary osmolality were measured hourly. Paired data from 4 girls and 15 boys with a mean age of 12.1 years were obtained. RESULTS: In the early response phase more than 25% of patients had a higher diuresis rate with tablet vs melt formulation, reaching statistical significance in the plateau phase (urine collected at hours 3 to 5, p <0.02) and in duration of action (urine collected at hours 5 to 8, p <0.005). For desmopressin melt smaller standard deviations in diuresis rate were remarkable. Concentrating capacity demonstrated no significant differences between formulations in the early response phase, in contrast to the plateau phase (p <0.036) and duration of action (p <0.001). CONCLUSIONS: With meal combination desmopressin melt formulation has a superior pharmacodynamic profile to tablet, making it more suitable for the younger age group with a limited interval between meal and drug administration.

Prospective evaluation of clinical voiding reeducation or voiding school for lower urinary tract conditions in children.

PURPOSE: We conducted a prospective controlled study evaluating the results of a clinical voiding reeducation program (voiding school) for treatment of lower urinary tract conditions in children compared to no treatment. MATERIALS AND METHODS: A total of 38 children with nonneurogenic lower urinary tract conditions were included in the study. Controls, consisting of 15 children on the waiting list for the same program, received no treatment. The clinical voiding reeducation program consisted of instruction on voiding and drinking, individualized voiding diaries, pelvic floor biofeedback training, uroflowmetry, alarm therapy, cognitive therapy and psychological support. Data on voiding, drinking, pelvic floor control, voided volume, uroflow, incontinence and stool habits were gathered before the program, during the program and 6 months after the program. In the control group the same data were gathered. RESULTS: In the study group a positive effect of voiding school was observed in 92% of children, with 42% becoming completely dry, 24% improving from incontinence during the day and night to incontinence during the day or night only, and 26% remaining incontinent. In all patients the number and amount of incontinence episodes decreased. In the control group no differences were observed between the start of study and 6 months later. The study group did significantly better on voided volume and incontinence compared to controls. CONCLUSIONS: In this prospective controlled study a positive effect was noted on voided volume and incontinence with a clinical voiding reeducation program (voiding school).

Population Pharmacokinetics of Unbound and Total Teicoplanin in Critically Ill Pediatric Patients.

BACKGROUND AND OBJECTIVES: Teicoplanin is a highly protein-bound antibiotic, increasingly used to treat serious Gram-positive infections in critically ill children. Maturational and pathophysiological intensive care unit-related changes often lead to altered pharmacokinetics. In this study, the objectives were to develop a pediatric population-pharmacokinetic model of unbound and total teicoplanin concentrations, to investigate the impact of plasma albumin levels and renal function on teicoplanin pharmacokinetics, and to evaluate the efficacy of the current weight-based dosing regimen. METHODS: An observational pharmacokinetic study was performed and blood samples were collected for quantification of unbound and total concentrations of teicoplanin after the first dose and in assumed steady-state conditions. A population-pharmacokinetic analysis was conducted using a standard sequential approach and Monte Carlo simulations were performed for a probability of target attainment analysis using previously published pharmacokinetic-pharmacodynamic targets. RESULTS: A two-compartment model with allometric scaling of pharmacokinetic parameters and non-linear plasma protein binding best described the data. Neither the inclusion of albumin nor the renal function significantly improved the model and no other covariates were supported for inclusion in the final model. The probability of target attainment analysis showed that the standard dosing regimen does not satisfactory attain the majority of the proposed targets. CONCLUSIONS: We successfully characterized the pharmacokinetics of unbound and total teicoplanin in critically ill pediatric patients. The highly variable unbound fraction of teicoplanin could not be predicted using albumin levels, which may support the use of therapeutic drug monitoring of unbound concentrations. Poor target attainment was shown for the most commonly used dosing regimen, regardless of the pharmacokinetic-pharmacodynamic target evaluated.

Neurocognitive functioning in school-aged cystinosis patients.

INTRODUCTION: Cystinosis is an autosomal recessive disorder leading to intralysosomal cystine accumulation in various tissues. It causes renal Fanconi syndrome and end stage renal failure around the age of 10 years if not treated with cysteamine. Children with cystinosis seem to have a normal intelligence but frequently show learning difficulties. These problems may be due to specific neurocognitive deficits rather than impaired renal function. Whether cysteamine treatment can improve cognitive functioning of cystinosis patients is thus far unknown. We aim to analyze neurocognitive functioning of school-aged cystinosis patients treated with cysteamine in order to identify specific deficits that can lead to learning difficulties. PATIENTS AND METHODS: Fourteen Dutch and Belgian school-aged cystinosis patients were included. Glomerular filtration rate was estimated using the Schwartz formula. Children were tested for general intelligence, visual-motor integration, inhibition, interference, sustained attention, accuracy, planning, visual memory, processing speed, motor planning, fluency and speed, and behavioural and emotional functioning using standardized methods. RESULTS: Glomerular filtration rate ranged from 22 to 120 ml min(-1) 1.73 m(-2). Median full-scale intelligence was below the average of a normal population (87, range 60-132), with a discrepancy between verbal (median 95, range 60-125) and performance (median 87, range 65-130) intelligence. Over 50% of the patients scored poorly on visual-motor integration, sustained attention, visual memory, planning, or motor speed. The other tested areas showed no differences between patients' and normal values. CONCLUSION: Neurocognitive diagnostics are indicated in cystinosis patients. Early recognition of specific deficits and supervision from special education services might reduce learning difficulties and improve school careers.

Acid-base disturbances in dehydrated patients with cystic fibrosis : four case reports with review of literature.

Most episodes of vomiting, reduced intake and diarrhoea in children can be evaluated and treated without additional tests. However, when the degree of clinical dehydration is not in line with the patient's medical history, other diagnoses should be suspected. In the presence of a hyponatraemic hypochloraemic metabolic alkalosis, cystic fibrosis (CF) should be included in the differential diagnosis, especially if there is failure to thrive even in the absence of respiratory symptoms. Furthermore, young patients diagnosed with CF have a higher risk for an acute electrolyte decompensation caused by increased salt and fluid losses. We present 4 paediatric cases to raise the awareness of electrolyte disturbances in CF patients.

The long-term added value of voiding school for children with refractory non-neurogenic overactive bladder: an inpatient bladder rehabilitation program.

INTRODUCTION & BACKGROUND: Despite adequate management, 20% of children with overactive bladder (OAB) syndrome fail to improve their bladder function. To approach the need for alternative strategies, an inpatient bladder rehabilitation 'voiding school' program was established. OBJECTIVE: The objective of this study was to evaluate the short- and long-term (1-year follow-up) outcome of this voiding school program in children with refractory OAB. In addition, the authors aimed to identify which children achieved the best outcomes with this voiding school program. STUDY DESIGN: The charts of all children (n = 357, mean age: 9.7 ± 2.0 years, 63.6% boys) with refractory OAB who attended voiding school between 2000 and 2010 were reviewed. A linear mixed model with random intercept was used to evaluate the incontinence (expressed by enuresis and daytime incontinence voiding scores) and maximal voiding volume (MVV). RESULTS & DISCUSSION: This study demonstrated an overall beneficial long-term effect of the inpatient program on day- and night-time incontinence, in which 36.6% of children achieved dryness during day- and night-time. In addition, the mean overall decline in the number of wet nights and days declined with 4 extra dry days and/or nights per week, in comparison with the level of continence before attending the voiding school program. In contrast, only a temporary increase in MVV was seen, however, without relapse incontinence. At last, the authors identified the negative impact of decreasing age, male sex, dysfunctional voiding and nocturnal polyuria on the overall outcome of the inpatient program. CONCLUSION: An inpatient rehabilitation 'voiding school' program is a successful and safe treatment modality for children with refractory OAB that results in long-term significant increase of continence, as well as amelioration in degree of severity. The worst outcomes of this voiding school program were detected in children with young age, who were boys, or had associated nocturnal polyuria, dysfunctional voiding, and/or faecal incontinence.

Desmopressin resistant nocturnal polyuria may benefit from furosemide therapy administered in the morning.

PURPOSE: There is increasing evidence that a subgroup of patients with monosymptomatic nocturnal enuresis and nocturnal polyuria resistant to desmopressin may have an abnormal circadian rhythm of renal tubular sodium handling. The pathogenesis of this phenomenon remains to be elucidated. If the increased sodium excretion overnight results in desmopressin resistance, decreasing the sodium excretion overnight may result in subsequently better desmopressin response. MATERIALS AND METHODS: We conducted a pilot study of the anti-enuretic and antidiuretic effects of desmopressin combined with 0.5 mg/kg furosemide daily in patients with desmopressin resistant nocturnal polyuria despite dietary sodium and protein restriction. Values were plotted against the reference frame of a desmopressin responsive enuresis group. RESULTS: Baseline values revealed significantly lower urinary osmolality and higher diuresis rate overnight compared to the reference population (monosymptomatic nocturnal enuresis desmopressin responders). Introduction of desmopressin resulted in normalization of nocturnal urinary osmolality. However, nocturnal polyuria persisted, despite reaching maximal urinary concentration overnight. Although protein and sodium restriction resulted in a significant decrease in urinary osmolality and diuresis rate, the difference was not clinically important enough to reach normal values or to achieve continence. Furosemide in the morning resulted in a significant increase in diuresis and osmotic and sodium excretion during the day, and decreased nighttime diuresis and osmotic excretion. In 9 of 12 patients the nocturnal antidiuretic effect resulted in an anti-enuretic effect, defined as enuresis less than 1 wet night per month. In 3 patients insufficient anti-enuretic effects were obtained despite significant antidiuresis. CONCLUSIONS: This pilot study clearly demonstrates that introduction of early morning furosemide results in a significantly lower nocturnal diuresis rate. Reduced diuresis associated with unchanged urinary osmolality results in decreased nocturnal osmotic excretion in compensation for increased osmotic (sodium) excretion during the daytime.

Nocturnal polyuria is related to 24-hour diuresis and osmotic excretion in an enuresis population referred to a tertiary center.

PURPOSE: Primary nocturnal enuresis is a heterogeneous disorder, causing a mismatch between overnight diuresis volume and functional bladder capacity. Despite increasing insights in pathogenesis, lack of efficacy of the available treatments is a major problem. We evaluated characteristics of bladder volume and diuresis rate in patients with nocturnal enuresis referred to a tertiary enuresis center. MATERIALS AND METHODS: Noninvasive screening including maximal voided volume, 24-hour circadian rhythm of diuresis and osmotic excretion from 1,000 consecutive patients. RESULTS: Of the patients referred as having monosymptomatic nocturnal enuresis 32% were subsequently classified as having nonmonosymptomatic nocturnal enuresis. Differences in bladder volume and nocturnal diuresis characteristics between the monosymptomatic nocturnal enuresis and nonmonosymptomatic nocturnal enuresis groups were minimal. CONCLUSIONS: The most common observation is a nocturnal diuresis volume greater than maximal voided volume, which in both groups can be caused by nocturnal polyuria or small bladder volume for patient age. The most striking observation is that the positive correlation between nocturnal diuresis volume rate and nocturnal osmotic excretion and 24-hour fluid intake is significantly higher than with the inversed urinary osmolality overnight, which is not only unexpected based on the theory of the primary suppression of vasopressin levels overnight, but also points to a more important role for nutritional and fluid intake than accepted, if not in the primary pathogenesis, then at least in therapy resistance.

Nocturnal polyuria is related to absent circadian rhythm of glomerular filtration rate.

PURPOSE: Monosymptomatic nocturnal enuresis is frequently associated with nocturnal polyuria and low urinary osmolality during the night. Initial studies found decreased vasopressin levels associated with low urinary osmolality overnight. Together with the documented desmopressin response, this was suggestive of a primary role for vasopressin in the pathogenesis of enuresis in the absence of bladder dysfunction. Recent studies no longer confirm this primary role of vasopressin. Other pathogenetic factors such as disordered renal sodium handling, hypercalciuria, increased prostaglandins and/or osmotic excretion might have a role. So far, little attention has been given to abnormalities in the circadian rhythm of glomerular filtration rate. We evaluated the circadian rhythm of glomerular filtration rate and diuresis in children with desmopressin resistant monosymptomatic nocturnal enuresis and nocturnal polyuria. MATERIALS AND METHODS: We evaluated 15 children (9 boys) 9 to 14 years old with monosymptomatic nocturnal enuresis and nocturnal polyuria resistant to desmopressin treatment. The control group consisted of 25 children (12 boys) 9 to 16 years old with monosymptomatic nocturnal enuresis without nocturnal polyuria. RESULTS: Compared to the control population, children with nocturnal polyuria lost their circadian rhythm not only for diuresis and sodium excretion but also for glomerular filtration rate. CONCLUSIONS: Patients with monosymptomatic nocturnal enuresis and nocturnal polyuria lack a normal circadian rhythm for diuresis and sodium excretion, and the circadian rhythm of glomerular filtration rate is absent. This absence of circadian rhythm of glomerular filtration rate and/or sodium handling cannot be explained by a primary role of vasopressin, but rather by a disorder in circadian rhythm of renal glomerular and/or tubular functions.

Reduced decrease of peripheral vascular resistance during exercise in young type I diabetic patients.

OBJECTIVE: In normal subjects, peripheral vascular resistance decreases during dynamic exercise. We studied blood pressure and peripheral vascular resistance responses to dynamic exercise in young normotensive type I diabetic patients. RESEARCH DESIGN AND METHODS: Thirty adolescent diabetic patients (9-19 years of age) underwent a maximal exercise test on a cycle ergometer. In a subset of 14 patients, cardiac output was measured by a CO2 rebreathing method and peripheral vascular resistance was calculated. Twenty-four normal individuals, age and sex matched, served as control subjects. RESULTS: Diastolic blood pressure was significantly higher in diabetic patients at intermediate workload (77 +/- 2 vs. 71 +/- 1 mmHg) and peak exercise (86 +/- 2 vs. 73 +/- 2 mmHg). Peripheral vascular resistance was significantly higher in diabetic patients at intermediate workload (17.0 +/- 1.1 vs. 12.6 +/- 0.5 mmHg.l-1.min-1.m-2) and peak exercise (16.3 +/- 1.3 vs. 11.4 +/- 0.5 mmHg.l-1.min-1.m-2). There were no significant correlations with the patient's age, diabetes duration, or diabetes control. CONCLUSIONS: We observed the decrease of vasodilator response during dynamic exercise in normotensive young type I diabetic patients.

Propylthiouracil induced ANCA-associated vasculitis in a 14-year-old girl.

BACKGROUND: Antineutrophil cytoplasmic antibodies (ANCAs) are the serologic hallmark of ANCA-associated primary small-vessel vasculitides (AAVs), but these antibodies have also been described in other autoimmune diseases such as inflammatory bowel diseases. Furthermore, different drugs are linked to the induction of ANCA, including propylthiouracil (PTU). However progression into clinical overt vasculitis is less common. CASE-DIAGNOSIS/TREATMENT: We describe the case of a young girl with Graves' disease presenting with fatigue, fever, episcleritis and arthritis. The unexpected double myeloperoxidase/proteinase 3-ANCA positivity triggered a multidisciplinary diagnostic work-up and resulted in the diagnosis of a clinically overt PTU-induced AAV. After PTU-withdrawal and treatment with high-dose corticosteroids, a favorable clinical and biochemical evolution was obtained. CONCLUSIONS: The use of PTU in the management of hyperthyroidism is not considered first-line treatment in Europe and is even less commonly used in children. Nevertheless, pediatricians should be aware of the possibility of PTU-induced AAV, especially in the presence of multiple ANCA reactivities. Therefore, the use of this drug should be weighed carefully in children.

Pituitary adenylate cyclase-activating polypeptide deficiency associated with increased platelet count and aggregability in nephrotic syndrome.

BACKGROUND: Pituitary adenylate cyclase-activating polypeptide (PACAP) was recently identified as an inhibitor of megakaryopoiesis and platelet aggregability. OBJECTIVE: We studied PACAP levels in children with nephrotic syndrome (NS), which is associated with thrombocytosis, platelet hyperaggregability, and an increased risk of thrombosis. PATIENTS/METHODS: In four children with congenital NS (CNS) and 24 children with idiopathic NS (INS), plasma and urine levels of PACAP and ceruloplasmin were measured, as were platelet counts and platelet aggregation responses to collagen. In CNS patients, in vitro megakaryopoiesis and nuclear factor-κB expression in platelet lysates were also measured. All tests were performed during the nephrotic state and the non-nephrotic state. RESULTS: Urinary losses of PACAP and ceruloplasmin were observed during the nephrotic state, and disappeared during the non-nephrotic state. Plasma PACAP deficiency was more pronounced in CNS patients than in INS patients. Thrombocytosis was observed in all CNS patients and in 11 of 29 INS patients during the nephrotic state. During the PACAP-deficient state, in vitro megakaryopoiesis was increased for CNS patients, and this effect could be reversed by the addition of recombinant PACAP. Platelet hyperaggregability was observed during the nephrotic state in both CNS and INS patients. In INS patients, the addition of recombinant PACAP to patients' platelets was studied, and resulted in decreased aggregation during the nephrotic state. Platelet aggregation correlated inversely with plasma PACAP levels, but not with serum albumin levels. CONCLUSIONS: We demonstrate urinary losses of PACAP and plasma PACAP deficiency in children with NS, associated with thrombocytosis and platelet hyperaggregability.

Outpatient pelvic-floor therapy in girls with daytime incontinence and dysfunctional voiding.

OBJECTIVES: Analysis of an experience in treating girls with dysfunctional voiding with an outpatient pelvic-floor therapy consisting of voiding and drinking schedule, pelvic-floor relaxation biofeedback, instructions on toilet behavior, and uroflowmetry. METHODS: The files of 50 girls (between 6 and 13 years of age) with urodynamically proven dysfunctional voiding who participated in the training program were analyzed retrospectively. Thirty-five girls received anticholinergics during the entire course of the training. The long-term absence of diurnal incontinence was used as the criterion for the success of the therapy. The duration of treatment before reaching this success was used as a parameter to measure the intensity of therapy. For a portion of the study group, a comparison is made with the duration of the preceding therapies to demonstrate indirectly the cumulative effect of the pelvic-floor therapy. RESULTS: Forty-six girls (92%) normalized their flow and bladder capacity after therapy and saw their daytime incontinence disappearing. All of these girls achieved this result in a maximum of 18 sessions within a 6-month period. At the follow-up examination after 6 months, five of the girls had relapsed (10%), which brings the ultimate success after 6 months of follow-up to 82%. CONCLUSIONS: Pelvic-floor therapy seems to be a reasonable and meaningful component in the treatment of bladder dysfunction in which detrusor-sphincter dyscoordination plays a role.

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.

Advantages of HCO3 solution with low sodium concentration over standard lactate solutions for acute peritoneal dialysis.

The aim of this study was to identify the advantages of a bicarbonate solution with a low sodium concentration. Twelve children (3 days-6 years) with acute renal failure (ARF), positive fluid balance, and lactate acidosis (> 40 mg/dL) were treated by automated peritoneal dialysis (APD) with frequent exchanges of small fill volumes of a hypertonic solution. For Day 1 we used PD1/PD4 Dianeal (3.86%) (Baxter). After 24 hours we switched to a HCO3 solution: 38 mmol/L, Na 128 mmol/L. As the control group, we studied retrospectively the last 12 children of the previous period who were treated with APD. The age distribution was 4 days to 4 years. No significant differences were found between the groups for serum creatinine, blood urea nitrogen, and fluid overload (Day 1 to Day 4). Although the values for lactate and Na were not different before the start of the study (Day 1) and after 24 hours of Dianeal (Day 2), they were significantly lower in the study group on Day 4 [HCO3 53 (23-83), Na 148 (137-136) mEq/L] than in the control group [lactate 148 (137-156), Na 154 (142-165) mEq/L]. A low sodium concentration results in higher sodium extraction, which is important for patients with fluid overload. Low sodium concentrations in APD are needed because the peritoneal membrane "sieves" the sodium during short dwells. HCO3 dialysis is a logical choice for patients with lactate acidosis, resulting in a significant lower serum lactate and increase of BE after 48 hours of treatment.

New perspectives for PD in acute renal failure related to new catheter techniques and introduction of APD.

Acute renal failure remains a major problem in pediatric intensive care unit (PICU) patients. Although in most handbooks peritoneal dialysis (PD) is still considered to be the first choice for children < 20 kg and there is some evidence that PD may preserve and/or favor recuperation of renal function, most PICU departments are using continuous veno-venous hemofiltration and dialysis or hemodialysis as treatment. The main reasons for this are workload for the PICU nurses, catheter problems, the risk of peritonitis, and limited ultrafiltration. In a retrospective study (1992-1995) in 46 patients (age 3 days to 14 years), automated PD (APD) was the initial treatment in 44 patients. Complications of the Seldinger-placed Cook (pleuropericard) catheter were limited: leakage (1/44); bleeding: n = 0; obstruction or dislocation: n = 4; peritonitis: n = 1 (Candida); ultrafiltration (UF) problems: n = 3. APD in children with acute renal function (ARF) is a good alternative for continuous veno-venous dialysis. Placement of a pigtail (Cook) catheter is a quick (10 min), safe procedure, with low leakage risk. This, together with the low manipulation rate, gives a low peritonitis rate. The use of the cycler makes frequent changes of small volumes possible, resulting in better clearance, good UF, no interference with hemodynamic or respiratory stability, and a reduced workload.