Does the development and use of modern disposable diapers affect bladder control? A systematic review.

INTRODUCTION AND OBJECTIVE: During the last decades, the development of the modern disposable diaper (DD) has changed the way we diaper our children, as they are safe, easy to use, comfortable and easy to dispose, compared to cloth diapers used earlier. Concurrently, the age of initiating toilet training (TT) is rising. We aimed to investigate the connection between DD usage and the tendencies seen in TT and childhood urinary incontinence, with specific interest on studies evaluating the effect of diapering on enuresis. STUDY DESIGN: A literature search was conducted in PubMed and Embase. A systematic literature search was conducted, revealing 309 studies in Embase and 269 studies in Pubmed. After removing duplicates, 400 studies were eligible for screening. All abstracts were screened, and 12 relevant abstracts where identified, but only eight studies were eligible. No prospective intervention studies specifically evaluating the effect of diaper on enuresis were identified. Literature on TT and diapers in general was identified using the respective search terms on both databases. RESULTS: The eight studies identified showed a tendency towards diaper use being related to a delay on obtaining continence in children, but no secure conclusions can be made, as the literature is inadequate. DISCUSSION AND CONCLUSION: Based on the available literature no secure conclusions can be drawn although an association is suggested. In order to evaluate the effect of diapers on incontinence, prospective randomized studies are needed.

Desmopressin use in pediatric nocturnal enuresis patients: is there a sex difference in prescription patterns?

Desmopressin is a long-established treatment for nocturnal enuresis with clear guidelines regarding its usage. A sex difference in renal sensitivity has recently been reported in adults. The objective of this study was to investigate real-life desmopressin prescription in the Danish pediatric population, and prescription patterns which may reflect a sex difference in pediatric usage. Formulation, dose, treatment duration, and safety (hyponatremia) were investigated. 40,596 children received 214,220 desmopressin prescriptions between 2004 and 2011 in the Danish National Prescription Registry. Data were linked to hyponatremia diagnoses from the National Patient Registry. Although the lowest recommended dose of desmopressin oral lyophilisate is 120 µg, around a fifth of children were prescribed 60 µg for long-term use. A greater proportion of girls (22.6%) than boys (19.8%) received this low dose. Treatment duration was longer for boys than girls on oral lyophilisate (mean 489-524 vs. 414-462 days) and tablet (0.1 mg: 204 vs. 161 days). Prescribed daily dose was consistent with time between prescriptions, indicating no significant drug holidays. There were no admissions for hyponatremia during the observation period. CONCLUSION: Danish national prescription data on pediatric desmopressin dosage are consistent with a greater sensitivity to desmopressin in girls than boys. Further studies are required. What is Known: • Desmopressin has been used for pediatric nocturnal enuresis for decades • Recent evidence suggests a sex difference in desmopressin sensitivity in adults What is New: • For the first time, desmopressin prescription practices in nocturnal enuresis are documented for an entire country • A higher proportion of girls than boys received a low dose of desmopressin, consistent with the sex difference in sensitivity reported in adults.

Evidence of reduced bladder capacity during nighttime in children with monosymptomatic nocturnal enuresis.

INTRODUCTION: Bladder capacity in children with nocturnal enuresis is assessed by maximal voided volumes (MVV) obtained through daytime frequency volume (FV) charts. Although a degree of association has been demonstrated, daytime MVV does not consistently correspond with the nocturnal bladder capacity (NBC) in monosymptomatic nocturnal enuresis (MNE). It was hypothesized that isolated reduced NBC is a common phenomenon in children with nocturnal enuresis, despite normal daytime bladder function. OBJECTIVE: The aim of this study was to evaluate NBC in children with MNE and normal daytime voided volumes. Specifically, it aimed to determine the prevalence and degree of reduced NBC when using nocturnal urine production (NUP) during wet nights as a surrogate estimate of NBC. Furthermore, it aimed to investigate the relationship between NBC and desmopressin response. MATERIALS AND METHODS: Data from 103 children aged 5-15 years consecutively treated for MNE in a tertiary referral centre and with normal MVV on daytime FV charts were collected for this cohort study. Home recordings were completed for 2 weeks at baseline and during desmopressin dose titration. Estimated nocturnal bladder capacity (eNBC) was assessed separately each night as the total NUP causing a wet night. If NUP during a wet night was less than MVV, it was considered to be reduced eNBC during that particular night. RESULTS: Surprisingly, 82% (n = 84) of the children with MNE and normal daytime MVV experienced at least one wet night, with NUP below the daytime MVV indicative of a reduced eNBC. For 84 patients, mean percentage of wet nights with reduced eNBC (NUP below MVV) was 49% (SD ± 31). A total of 11% of children with frequently reduced eNBC (>40% of wet nights with reduced eNBC) responded to desmopressin (Summary Fig.). Of the children with frequently reduced NBC, 91% experienced wet nights, with NUP <65% of expected bladder capacity (EBC). CONCLUSIONS: A significant proportion of children with MNE and normal MVV during the daytime frequently experienced wet nights, with a NUP well below their MVV and even <65% of EBC. This indicated that bladder reservoir dysfunction during sleep is relatively common in MNE. This abnormality was not reflected on daytime recordings, and thus nighttime data with NUP must be collected. This phenomenon may explain treatment failure to desmopressin, despite adequate antidiuretic response.

Reduced sCD36 following weight loss corresponds to improved insulin sensitivity, dyslipidemia and liver fat in obese children.

BACKGROUND/OBJECTIVES: Childhood obesity is a major health problem with serious long-term metabolic consequences. CD36 is important for the development of obesity-related complications among adults. We aimed to investigate circulating sCD36 during weight loss in childhood obesity and its associations with insulin resistance, dyslipidemia, hepatic fat accumulation and low-grade inflammation. SUBJECTS/METHODS: The impact of a 10-week weight loss camp for obese children (N=113) on plasma sCD36 and further after a 12-month follow-up (N=68) was investigated. Clinical and biochemical data were collected, and sCD36 was measured by an in-house assay. Liver fat was estimated by ultrasonography and insulin resistance by the homeostasis model assessment (HOMA-IR). RESULTS: Along with marked weight loss, sCD36 was reduced by 21% (P=0.0013) following lifestyle intervention, and individual sCD36 reductions were significantly associated with the corresponding decreases in HOMA-IR, triglycerides and total cholesterol. The largest sCD36 decrease occurred among children who reduced HOMA-IR and liver fat. After 12 months of follow-up, sCD36 was increased (P=0.014) and the metabolic improvements were largely lost. CONCLUSIONS: Weight-loss-induced sCD36 reduction, coincident with improved insulin resistance, circulating lipids and hepatic fat accumulation, proposes that sCD36 may be an early marker of long-term health risk associated with obesity-related complications.

Carfilzomib alters the HLA-presented peptidome of myeloma cells and impairs presentation of peptides with aromatic C-termini.

Recent studies suggest that multiple myeloma is an immunogenic disease, which might be effectively targeted by antigen-specific T-cell immunotherapy. As standard of care in myeloma includes proteasome inhibitor therapy, it is of great importance to characterize the effects of this treatment on HLA-restricted antigen presentation and implement only robustly presented targets for immunotherapeutic intervention. Here, we present a study that longitudinally and semi-quantitatively maps the effects of the proteasome inhibitor carfilzomib on HLA-restricted antigen presentation. The relative presentation levels of 4780 different HLA ligands were quantified in an in vitro model employing carfilzomib treatment of MM.1S and U266 myeloma cells, which revealed significant modulation of a substantial fraction of the HLA-presented peptidome. Strikingly, we detected selective down-modulation of HLA ligands with aromatic C-terminal anchor amino acids. This particularly manifested as a marked reduction in the presentation of HLA ligands through the HLA allotypes A*23:01 and A*24:02 on MM.1S cells. These findings implicate that carfilzomib mediates a direct, peptide motif-specific inhibitory effect on HLA ligand processing and presentation. As a substantial proportion of HLA allotypes present peptides with aromatic C-termini, our results may have broad implications for the implementation of antigen-specific treatment approaches in patients undergoing carfilzomib treatment.

Short-term effects of liraglutide on kidney function and vasoactive hormones in type 2 diabetes: a randomized clinical trial.

AIMS: To investigate the effects of a single dose of 1.2 mg liraglutide, a once-daily glucagon-like peptide-1 (GLP-1) receptor agonist, on key renal variables in patients with type 2 diabetes. METHODS: The study was a placebo-controlled, double-blind, crossover trial in 11 male patients with type 2 diabetes. Measurements included (51) Cr-EDTA plasma clearance estimated glomerular filtration rate (GFR) and MRI-based renal blood flow (RBF), tissue perfusion and oxygenation. RESULTS: Liraglutide had no effect on GFR [95% confidence interval (CI) -6.8 to 3.6 ml/min/1.73 m(2) ] or on RBF (95% CI -39 to 30 ml/min) and did not change local renal blood perfusion or oxygenation. The fractional excretion of lithium increased by 14% (p = 0.01) and sodium clearance tended to increase (p = 0.06). Liraglutide increased diastolic and systolic blood pressure (3 and 6 mm Hg) and heart rate (2 beats per min; all p < 0.05). Angiotensin II (ANG II) concentration decreased by 21% (p = 0.02), but there were no effects on other renin-angiotensin system components, atrial natriuretic peptides (ANPs), methanephrines or excretion of catecholamines. CONCLUSIONS: Short-term liraglutide treatment did not affect renal haemodynamics but decreased the proximal tubular sodium reabsorption. Blood pressure increased with short-term as opposed to long-term treatment. Catecholamine levels were unchanged and the results did not support a GLP-1-ANP axis. ANG II levels decreased, which may contribute to renal protection by GLP-1 receptor agonists.

The effect of puberty on diurnal sodium regulation.

The aim of this study was to investigate the impact of sex and puberty stage on circadian changes in sodium excretion, sodium-regulating hormones, and hemodynamics. Thirty-nine healthy volunteers (9 prepuberty boys, 10 prepuberty girls, 10 puberty boys, and 10 puberty girls) were included. They all underwent a 24-h circadian in-patient study under standardized conditions regarding activity, diet, and fluid intake. Blood samples were drawn every 4 h, and the urine was collected in fractions. Blood pressure and heart rate were noninvasively monitored. Atrial natriuretic peptide (ANP), angiotensin II, aldosterone, and renin were measured in blood. Children in puberty had lower plasma levels of renin (P<0.05) and angiotensin II (P<0.05) and a 26% reduction in filtered sodium without changes in sodium excretion compared with prepuberty children. A circadian rhythm in sodium excretion, the renin-angiotensin system, ANP, and blood pressure was found with a midnight ANP peak (P<0.001), a nighttime decrease in hemodynamic parameters (P<0.001), an increase in plasma renin (P<0.001) and angiotensin II (P<0.001), and a decrease in sodium excretion (P<0.001) mainly on the basis of increased sodium reabsorption (P<0.001). The timing of the changes did not depend on sex or puberty group. There is a circadian rhythm of sodium excretion and sodium regulation in 7- to 15-yr-old children. This rhythm is similar in boys and girls. As an important new finding, puberty changes the plasma levels of renin and angiotensin II without changing the amount of sodium excreted or the day to night sodium excretion ratio.

The macrophage activation marker sCD163 is associated with changes in NAFLD and metabolic profile during lifestyle intervention in obese children.

BACKGROUND: Obesity is associated with metabolic derangement and non-alcoholic fatty liver disease (NAFLD). Macrophages are involved in liver inflammation and fibrosis, and soluble (s)CD163 is a macrophage activation marker. OBJECTIVES: To associate sCD163 with parameters of paediatric obesity and NAFLD, as well as changes in these parameters during lifestyle intervention. METHODS: We studied 117 obese children during a 10-week lifestyle intervention; 71 completed the 12-month follow-up. We recorded clinical and biochemical data, and performed liver ultrasonography. RESULTS: Baseline sCD163 was higher in children with elevated alanine transaminase (ALT) (2.3 ± 0.7 vs. 2.0 ± 0.6 mg L(-1), P = 0.03), steatosis (2.3 ± 0.7 vs. 2.0 ± 0.6 mg L(-1), P = 0.01) and high paediatric NAFLD fibrosis index (2.3 ± 0.7 vs. 1.9 ± 0.6 mg L(-1) , P = 0.03). Baseline sCD163 was independently associated with ALT, cholesterol and high-sensitivity C-reactive protein (hs-CRP). The change in sCD163 during lifestyle intervention was associated with changes in ALT, homeostatic model assessment of insulin resistance (HOMA-IR), hs-CRP and cholesterol, and inversely associated with the change in high-density lipoprotein cholesterol. CONCLUSION: sCD163 was associated with markers of liver injury and metabolic parameters in obese children, and changes in these parameters during lifestyle intervention. This may suggest that activated macrophages play a role in NAFLD and sCD163 may serve as a marker of liver disease severity and treatment effect.

National Surveillance of Central Diabetes Insipidus (CDI) in Denmark: results from 5 years registration of 9309 prescriptions of desmopressin to 1285 CDI patients.

CONTEXT: Epidemiological data for central diabetes insipidus (CDI) are sparse. OBJECTIVE: The purpose of this study was to provide accurate epidemiological data on CDI on a national level. DESIGN AND SETTING: This was a drug utilization and patient registry study during a 5-year period from 2007 to 2011. METHODS: We used the Danish National Prescription Registry data linked with the Danish National Patient Registry to study the epidemiology of CDI using waiting time distribution and other pharmacoepidemiological methods. PATIENTS: A total of 1285 patients with CDI were recorded in the observation period and given 9309 prescriptions for desmopressin in the nasal formulation, orodispersible tablet, or conventional tablet. RESULTS: The period prevalence rate of CDI in Denmark over the 5-year period investigated was 23 CDI patients per 100 000 inhabitants, with a higher prevalence in children and older adults (>80 years of age). The 1-year period prevalence rate of CDI decreased in Denmark over the 5 years from approximately 10 to 7 CDI patients per 100 000 inhabitants. The yearly incidence rate of new cases of CDI was found to be 3 to 4 patients per 100 000. The incidence of (presumable) congenital CDI was found to be 2 infants per 100 000 infants. Half of the patients with CDI prescribed as oral treatment were provided dosing instructions to only administer the drug before bedtime, and one third of the CDI patients either had no specific instructions or were instructed to use the drug as needed. Hospital admissions due to severe hyponatremia occurred in 0.9% of patients over a 5-year period, predominantly in females with an incidence ratio of women to men of 1.8:1. CONCLUSION: Half of the cases of CDI are acquired later in life. At least half of the patients with CDI are instructed to prevent nocturnal polyuria, but it is not clear whether their CDI remains uncontrolled during the daytime or, alternatively, whether they use desmopressin only as needed. Female patients with CDI had approximately twice the number of hospital admissions due to severe hyponatremia than male patients with CDI.

Puberty alters renal water handling.

We investigated the influence of sex and puberty stage on circadian urine production and levels of antidiuretic hormone [arginine vasopressin (AVP)] in healthy children. Thirty-nine volunteers (9 prepuberty boys, 10 prepuberty girls, 10 midpuberty boys, and 10 midpuberty girls) were included. All participants underwent a 24-h circadian inpatient study under standardized conditions regarding Na(+) and fluid intake. Blood samples were drawn every 4 h for measurements of plasma AVP, serum 17-ß-estradiol, and testosterone, and urine was fractionally collected for measurements of electrolytes, aquaporin (AQP)2, and PGE2. We found a marked nighttime decrease in diuresis (from 1.69 ± 0.08 to 0.86 ± 0.06 ml·kg(-1)·h(-1), P < 0.001) caused by a significant nighttime increase in solute-free water reabsorption (TcH2O; day-to-night ratio: 0.64 ± 0.07, P < 0.001) concurrent with a significant decrease in osmotic excretion (day-to-night ratio: 1.23 ± 0.06, P < 0.001). Plasma AVP expressed a circadian rhythm (P < 0.01) with a nighttime increase and peak levels at midnight (0.49 ± 0.05 pg/ml). The circadian plasma AVP rhythm was not influenced by sex (P = 0.56) or puberty stage (P = 0.73). There was significantly higher nighttime TcH2O in prepuberty children. This concurred with increased nighttime urinary AQP2 excretion in prepuberty children. Urinary PGE2 exhibited a circadian rhythm independent of sex or puberty stage. Levels of serum 17ß-estradiol and testosterone were as expected for sex and puberty stage, and no effect on the AVP-AQP2-TcH2O axis was observed. This study found a circadian rhythm of plasma AVP independent of sex and puberty stage, although nighttime TcH2O was higher and AQP2 excretion was more pronounced in prepuberty children, suggesting higher prepuberty renal AVP sensitivity.

Genetics of steroid-resistant nephrotic syndrome: a review of mutation spectrum and suggested approach for genetic testing.

UNLABELLED: Identification of genes, associated mutations and genotype-phenotype correlations in steroid-resistant nephrotic syndrome (SRNS) is being translated to clinical practice through genetic testing. This review provides an update on the genes and mutations associated with SRNS along with a suggested approach for genetic testing in patients with SRNS. CONCLUSION: The number of indentified genes associated with SRNS is increasing along with our understanding of their impact on treatment response and risk of recurrence. A systematic approach to genetic testing in patients with SRNS might aid the physician in selecting appropriate treatment.

A novel deletion partly removing the AVP gene causes autosomal recessive inheritance of early-onset neurohypophyseal diabetes insipidus.

Familial neurohypophyseal diabetes insipidus (FNDI) typically presents with age-dependent penetrance and autosomal dominant inheritance caused by missense variations in one allele of the AVP gene encoding the arginine vasopressin (AVP) prohormone. We present the molecular genetic characteristics underlying an unusual form of FNDI occurring with very early onset and seemingly autosomal recessive inheritance. By DNA amplification and sequencing, we identified a novel variant allele of the AVP gene carrying a 10,396 base pair deletion involving the majority of the AVP gene as well as its regulatory sequences in the intergenic region between the AVP and the OXT gene, encoding the oxytocin prohormone. We found two chromosomes carrying the deletion in affected family members and one in unaffected family members suspected to transmit the deleted allele. Whole-genome array analysis confirmed the results and excluded the presence of any additional major pathogenic abnormalities. The deletion is predicted to abolish the transcription of the AVP gene, thus the fact that family members heterozygous for the deletion remain healthy argues, in general, against haploinsufficiency as the pathogenic mechanism FNDI. Accordingly, our data is strong support to the prevailing idea that dominant inheritance of FNDI is due to a dominant-negative effect exerted by variant AVP prohormone.

Sleep deprivation induces excess diuresis and natriuresis in healthy children.

Urine production is reduced at night, allowing undisturbed sleep. This study was undertaken to show the effect of sleep deprivation (SD) on urine production in healthy children. Special focus was on gender and children at an age where enuresis is still prominent. Twenty healthy children (10 girls) underwent two 24-h studies, randomly assigned to either sleep or SD on the first study night. Diet and fluid intake were standardized. Blood samples were drawn every 4 h during daytime and every 2 h at night. Urine was fractionally collected. Blood pressure and heart rate were noninvasively monitored. Blood was analyzed for plasma antidiuretic hormone (AVP), atrial natriuretic peptide (ANP), angiotensin II, aldosterone, and renin. Urine was analyzed for aquaporin-2 and PGE(2). Successful SD was achieved in all participants with a minimum of 4 h 50 min, and full-night SD was obtained in 50% of the participants. During SD, both boys and girls produced markedly larger amounts of urine than during normal sleep (477 ± 145 vs. 291 ± 86 ml, P < 0.01). SD increased urinary excretion of sodium (0.17 ± 0.05 vs. 0.10 ± 0.03 mmol·kg(-1)·h(-1)) whereas solute-free water reabsorption remained unchanged. SD induced a significant fall in nighttime plasma AVP (P < 0.01), renin (P < 0.05), angiotensin II (P < 0.001), and aldosterone (P < 0.05) whereas plasma ANP levels remained uninfluenced (P = 0.807). Nighttime blood pressure and heart rate were significantly higher during SD (mean arterial pressure: 78.5 ± 8.0 vs. 74.7 ± 8.7 mmHg, P < 0.001). SD leads to natriuresis and excess diuresis in healthy children. The underlying mechanism could be a reduced nighttime dip in blood pressure and a decrease in renin-angiotensin-aldosterone system levels during sleep deprivation.

Effect of laser acupuncture for monosymptomatic nocturnal enuresis on bladder reservoir function and nocturnal urine output.

PURPOSE: The alternative treatments for enuresis have been reported with high efficacy but in noncontrolled studies. Therefore, using a prospective, single-blind, randomized, placebo controlled design we evaluated the effect of laser acupuncture on bladder reservoir function and enuresis frequency in cases of monosymptomatic nocturnal enuresis with reduced maximal voided volume. MATERIALS AND METHODS: A total of 31 patients with monosymptomatic nocturnal enuresis, with at least 3 enuretic nights per week and less than 70% of normal age related maximal voided volume without first morning void (Koff's formula), no constipation, urinary tract abnormalities, or daytime incontinence were randomized into group 1--active laser acupuncture, group 2--placebo treatment with red light and skin contact and group 3--placebo treatment with red light without skin contact. After a 2-week run-in period (when patients made home recordings of nocturnal urinary production and during 2 weekends frequency-volume charts), the patients started a 5-week treatment. During the last 2 weeks of treatment patients performed the same recordings as during the run-in period. RESULTS: We found no significant effect of active laser acupuncture on maximal voided volume (first morning void excluded), maximal morning voided volume, voiding frequency, enuresis frequency before and after treatment or nocturnal urine production among the patient groups. However, we found that laser acupuncture resulted in a significant increase in average daytime voided volume. We found no effect of skin contact during placebo laser acupuncture. CONCLUSIONS: Laser acupuncture is a safe but inefficient treatment for monosymptomatic nocturnal enuresis with reduced maximal voided volume. However, we found subtle effects on bladder reservoir function.

Abnormal diurnal rhythm of urine output following renal transplantation: the impact of blood pressure and diuretics.

BACKGROUND: Nocturnal polyuria is the excretion at night of an excessive volume of urine. A major problem following renal transplantation is an abnormal diurnal rhythmicity in urine output. The purpose of this study was to elucidate the prevalence of nocturnal polyuria among renal transplant recipients in the early period after transplantation as well as at least 1 year after transplantation. We aimed to explore possible pathophysiological mechanisms behind nocturnal polyuria in this group of patients, focusing on the impact of blood pressure and medication. METHODS: Seventeen recently transplanted patients 17 late transplant recipients, and 17 healthy controls were included in the study. Voiding habits were assessed by completion of a frequency-volume chart recording all fluid intakes and voiding. A concomitant 24-hour blood pressure profile was obtained in all. RESULTS: Renal transplant recipients had a high prevalence of nocturnal polyuria (74%) and a disturbed blood pressure profile with a lack of appropriate nocturnal dipping (P < .0001) compared to controls. We found a positive correlation between increased nocturnal blood pressure and urine output at night (r = .368, P = .008). Patients taking diuretics had a circadian diurnal rhythm of urine output and a blood pressure profile similar to controls. CONCLUSIONS: Nocturnal polyuria was very common among both recent and late transplant recipients. A high fluid intake during daytime and hypervolemia were suggested as causes of a disturbed blood pressure profile, which partly seemed to explain the high urine output at night. Daytime diuretics may be an effective treatment of this inconvenient complication.

Effect of weight reduction on insulin sensitivity, sex hormone-binding globulin, sex hormones and gonadotrophins in obese children.

OBJECTIVE: Obesity in men is associated with reduced insulin sensitivity and hypoandrogenism, while obesity in women is associated with reduced insulin sensitivity and hyperandrogenism. In children, the effect of obesity and weight reduction on the hypothalamo-pituitary-gonadal axis is rarely investigated. The aim of the present study was to investigate the effect of weight reduction in obese Caucasian children on insulin sensitivity, sex hormone-binding globulin (SHBG), DHEAS and the hypothalamo-pituitary-gonadal axis. METHODS: One hundred and sixteen (65 females) obese children with a median age of 12.3 (7-15) years were examined before and after a 10-week stay at a weight loss camp. Examination included anthropometry and fasting blood samples measuring plasma glucose, serum insulin, SHBG, DHEAS, testosterone, 17ß-oestradiol, FSH and LH. RESULTS: Body mass index (BMI) decreased (P<0.01), insulin sensitivity and SHBG increased (P<0.01), independent of gender and puberty. The changes in insulin sensitivity and the changes in SHBG correlated significantly (P<0.01) independent of gender, puberty and the changes in BMI. Testosterone increased in boys (P<0.01) and tended to decrease in girls (P=0.05, in girls after menarche (P=0.03)). FSH increased in boys and girls. LH increased in boys and was unchanged in girls. CONCLUSIONS: During weight loss, insulin sensitivity and SHBG increased significantly in obese children, and the changes in insulin sensitivity and the changes in SHBG correlated significantly independent of gender, puberty and the changes in BMI. There was sexual dimorphism in the changes of testosterone, with the changes in boys towards increased virilisation and the changes in girls towards less virilisation.

Age related nocturnal urine volume and maximum voided volume in healthy children: reappraisal of International Children's Continence Society definitions.

PURPOSE: We determined normal, age related reference data regarding maximum voided volume and nocturnal urine production using the same methodology as in clinical practice. MATERIALS AND METHODS: A total of 62 girls and 86 boys without enuresis (mean +/- SD age 9.64 +/- 2.63 years, range 3 to 15) completed 4 days (2 weekends) of frequency-volume charts and 14 days of home recording of nocturnal urine production. From these recordings maximum voided volume with and without first morning void was derived for each subject. Also, average nocturnal urine volume with and without nocturia was calculated. Percentiles were produced by dividing the population into 1-year age groups. RESULTS: Based on 2,836 daytime voids and 1,977 overnight recordings, maximum voided volume and nocturnal urine volume showed a significant linear relationship with age but not with gender. Maximum voided volume with first morning void was significantly higher than without (403 +/- 137 ml vs 281 +/- 112 ml, p <0.0001) and the 50th percentile line of maximum voided volume with first morning void was 80 to 100 ml higher than Koff's formula (30 x [age + 1] ml). Conversely the 50th percentile of maximum voided volume without first morning void was almost identical to Koff's formula. Regarding nocturnal measurements, nocturia was noted on 128 nights (6.5%) and nocturnal urine volume on nights with nocturia was significantly higher than on nights without nocturia (365 +/- 160 ml vs 248 +/- 75 ml, respectively, p <0.0001). The 97.5th nocturnal urine volume percentile line of healthy children deviated markedly from the current International Children's Continence Society definition of nocturnal polyuria, especially at low and high ages. CONCLUSIONS: We demonstrate clearly that the universally used formula 30 x (age + 1) ml is indeed valid for a population of healthy Danish children but only if the first morning void is disregarded. Furthermore, we question the validity of the current International Children's Continence Society formula for nocturnal polyuria (nocturnal urine volume greater than 130% of maximum voided volume for age), and instead we propose the formula, nocturnal urine volume greater than 20 x (age + 9) ml.

Early high-dose immunosuppression in Henoch-Schönlein nephrotic syndrome may improve outcome.

OBJECTIVE: Renal involvement in Henoch-Schönlein purpura (HSP) constitutes a risk of end-stage renal disease (ESRD), especially in patients presenting with nephrotic syndrome. PATIENTS AND METHODS: The clinical courses of six patients (mean age 13.2 years; four boys and two girls) admitted from 2000 to 2007 with HSP and nephrotic syndrome were reviewed. Average follow-up was 44 months (28-59). Treatment protocols included oral prednisolone and in non-responders cyclosporin A, cyclophosphamide, mycophenolate mofetil or tacrolimus. Five patients were treated immediately after presentation of nephrotic syndrome/nephrotic range proteinuria (median 277 mg/m(2)/h). The last patient was treated locally with low-dose prednisolone (0.2-0.9 mg/kg/day) and 3 months of low-dose cyclophosphamide (1 mg/kg/day). RESULTS: All five patients treated promptly with high-dose immunosuppressant had normal estimated glomerular filtration rate (eGFR) (median 159 ml/min/1.73 m(2)) at follow-up. One obtained complete remission, two had positive dipstick proteinuria and two needed angiotensin-converting enzyme inhibitors to stay normotensive. The patient receiving low-dose immunosuppression at onset progressed to ESRD 44 months later. At initial presentation eGFR, blood pressure, renal biopsy grading, proteinuric range and plasma albumin were similar in all patients. CONCLUSION: Follow-up data from the patients suggest that an early aggressive immunosuppressive approach improves long-term renal outcome in HSP patients with nephrotic syndrome.

Basis and therapeutical rationale of the urinary concentrating mechanism.

The urine-concentrating mechanism performs one of the most essential functions in water and electrolyte metabolism and serves primarily to maintain extracellular osmolality within a very narrow range. The history of anti-diuresis dates back more than 100 years and includes the discovery of antidiuretic hormone (AVP), the renal AVP receptor, and most recently the water channel (aquaporin) proteins. Today, the mechanisms of antidiuresis are understood on a highly detailed molecular level including both short term and long-term regulation of AQP2 function. Furthermore, the background behind many acquired and inherited disturbances of water balance has now been revealed and has enabled a precise differential diagnosis. These include different forms of diabetes insipidus, nocturnal enuresis and nocturia in the elderly. Diabetes insipidus represents a dramatic but rare disturbance of water balance caused by deficient AVP secretion (neurogenic), reduced renal sensitivity to AVP (nephrogenic), an abnormally high fluid intake (primary polydipsia), or in rare cases by placental enzymatic degradation of AVP (gestational). Nocturnal enuresis and nocturia in the elderly represents much more common disturbances and share common pathogenic features including an abnormally high nocturnal urine production. This seems at least in part to be caused by abnormally low levels of plasma AVP during night. The increased understanding of such water balance disturbances have changed dramatically prior treatment practice by introducing antidiuresis as a treatment modality. The ongoing progress in our understanding of antidiuresis may provide the basis for the development of new antidiuretic compounds.

A randomised comparison of oral desmopressin lyophilisate (MELT) and tablet formulations in children and adolescents with primary nocturnal enuresis.

AIMS: Desmopressin is a useful treatment for primary nocturnal enuresis (PNE), a common childhood condition that can persist into adolescence. This open-label, randomised, cross-over study evaluated the preference of children and adolescents with PNE for sublingual desmopressin oral lyophilisate (MELT) vs. tablet treatment, and the efficacy, safety, compliance and ease of use associated with each formulation. In total, 221 patients aged 5-15 years who were already receiving desmopressin tablets were randomised 1 : 1 to receive desmopressin treatment in the order MELT/tablet (n = 110) or tablet/MELT (n = 111) for 3 weeks each. Each formulation was administered in bioequivalent doses (0.2/0.4 mg tablets identical with 120/240 microg MELT). Following treatment, patients were questioned regarding treatment preference. Diary card data and 100 mm Visual Analogue Scale scores were also recorded. RESULTS: Overall, patients preferred the MELT formulation to the tablet (56% vs. 44%; p = 0.112). This preference was age dependent (p = 0.006); patients aged < 12 years had a statistically significant preference for desmopressin MELT (p = 0.0089). Efficacy was similar for both formulations (MELT: 1.88 +/- 1.94 bedwetting episodes/week; tablet: 1.90 +/- 1.85 episodes/week). Ease of use of both formulations was high. Compliance (> or = 80%) was 94.5% for MELT patients vs. 88.9% for the tablet (p = 0.059). No serious/severe adverse events were reported. CONCLUSIONS: There was an overall preference for the MELT, and a statistically significant preference for desmopressin MELT in children aged 5-11 years. Desmopressin MELT had similar levels of efficacy and safety at lower dosing levels than the tablet, and therefore facilitates early initiation of PNE treatment in children aged 5-6 years.