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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 51Cr-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 m2] 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. [ABSTRACT FROM AUTHOR]

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 s CD163 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 s CD163 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 s CD163 was independently associated with ALT, cholesterol and high-sensitivity C-reactive protein (hs- CRP). The change in s CD163 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 s CD163 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 s CD163 may serve as a marker of liver disease severity and treatment effect. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Christensen JH, Kvistgaard H, Knudsen J, Shaikh G, Tolmie J, Cooke S, Pedersen S, Corydon TJ, Gregersen N, Rittig S. 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. [ABSTRACT FROM AUTHOR]

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 ≡ 120/240 μg 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 (≥ 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. [ABSTRACT FROM AUTHOR]

Deals with a study which demonstrated that male patients with nocturnal polyuria and age-matched controls without nocturia had a diurnal variation in functional bladder capacity with higher nighttime values. Background to the study; Material and methods; Results; Discussion.

Objective To collate data on voiding patterns at baseline (no treatment) and during short-term desmopressin treatment, with special reference to the functional and the mean bladder capacity. Patients and methods The study included 120 children (aged 6–16 years) with monosymptomatic nocturnal enuresis. While at home they recorded their fluid intake and diuresis in two separate periods, i.e. 2 weeks as a baseline registration and another 2 weeks during desmopressin titration. On four study days the children recorded the time and volume of all voids and of fluid intake. From the diaries their functional and mean bladder capacities, 24-h diuresis and day/night ratio of diuresis were determined. Results The mean 24-h diuresis was significantly lower during short-term desmopressin treatment. In most of the enuretics the mean day/night ratio increased on desmopressin treatment. The mean functional and mean bladder capacities were unaffected by desmopressin. Those not responding had bladder capacities of ≈ 100 mL less than full responders. Regardless of response, practically all the enuretics in the study had a smaller functional bladder capacity than expected for their age. Among responders the morning void was significantly larger than the following voids during the day, and among non-responders the fourth void was significantly larger than the previous voids in the day. Desmopressin treatment did not influence these volumes significantly. Conclusions Short-term desmopressin treatment does not affect functional and mean bladder capacity; 24-h urine production was reduced significantly (P <0.01) during desmopressin treatment. [ABSTRACT FROM AUTHOR]

OBJECTIVE The effect of food ingestion on the gastrointestinal absorption and antidiuretic action of oral desmopressin. An oral preparation of desmopressin, a synthetic analogue of vasopressin, has recently become available for clinical use. DESIGN A randomized, single-blind, crossover study with four treatment arms. Day A, no meal + placebo; B, no meal + 400 μg oral desmopressin; C, standard meal + 400 μg oral desmopressin; D, standard meal + 400 μg oral desmopressin after 1.5 hours. Plasma desmopressin was measured every 15–30 minutes for 6 hours after drug intake. An intravenous hydration regimen was employed on each study day. SUBJECTS Sixteen healthy, non-smoking, men aged 20–35 years (mean 27.8 years). MEASUREMENTS Plasma desmopressin concentrations were measured throughout each study day to calculate the area under the desmopressin plasma-concentration–time curve to infinity (AUCinf ), the maximum plasma desmopressin concentration (Cmax ), the time at which Cmax was reached (Tmax ) and the time at which plasma desmopressin was first detected (Tlag ). Urine volume, urine osmolality and plasma sodium concentrations were also measured at specified times on each study day. RESULTS The total absorption of oral desmopressin, reflected by the AUCinf , was significantly higher when taken during the fasting state (day B) compared with its administration with or 1.5 hours after a standard meal (days C and D). In addition, Cmax was higher and both Tmax and Tlag were shorter on day B compared with days C and D. No effect of food ingestion was observed on the pharmacodynamics of oral desmopressin: urine volume was decreased and urine osmolality was increased to similar extents on all active treatment days (B, C and D). No significant reductions in plasma sodium concentrations (a safety parameter) was observed during the trial.... [ABSTRACT FROM AUTHOR]

Examines the molecular genetic, clinical and psychiatric associations in nocturnal enuresis. Indication of clinical and genetic heterogeneity of nocturnal enuresis; Effects of combined primary nocturnal enuresis and voiding postponement; Presence of similar DNA-polymorphism for marker D8S260.

Aim: Bartter syndrome is an autosomal-recessive inherited disease in which patients present with hypokalaemia and metabolic alkalosis. We present two apparently nonrelated cases with antenatal Bartter syndrome type I, due to a novel variant in the SLC12A1 gene encoding the bumetanide-sensitive sodium-(potassium)-chloride cotransporter 2 in the thick ascending limb of the loop of Henle., Methods: Blood samples were received from the two cases and 19 of their relatives, and deoxyribonucleic acid was extracted. The coding regions of the SLC12A1 gene were amplified using polymerase chain reaction, followed by bidirectional direct deoxyribonucleic acid sequencing., Results: Each affected child in the two families was homozygous for a novel inherited variant in the SLC12A1gene, c.1614T>A. The variant predicts a change from a tyrosine codon to a stop codon (p.Tyr538Ter). The two cases presented antenatally and at six months of age, respectively., Conclusion: The two cases were homozygous for the same variant in the SLC12A1 gene, but presented clinically at different ages. This could eventually be explained by the presence of other gene variants or environmental factors modifying the phenotypes. The phenotypes of the patients were similar to other patients with antenatal Bartter syndrome., (©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Aim: To investigate the effect of treating defecation problems on urinary incontinence in children suffering from combined urinary bladder and bowel dysfunction (BBD)., Methods: We established a clinical database from medical records of all children referred to the urinary incontinence and gastroenterology outpatient clinics with BBD. The following variables were extracted: symptoms of constipation, faecal incontinence, urinary incontinence, age at onset of symptoms, treatment, including duration and response. All children went through the same treatment protocol. Faecal disorders were treated primarily and once relieved, the daytime incontinence was managed and followed by intervention for nocturnal enuresis., Results: In total, 73 children were included in the study. The treatment regimen resulted in resolution of the defecation disorder in 96% of the patients. Of the children with daytime urinary incontinence, 68% had at least a 50% reduction in number of daytime incontinence episodes by successful relief of bowel dysfunction and 27% became completely continent during daytime. Only 17% of the children suffering from enuresis had a significant reduction in number of wet nights after relief of their faecal problem., Conclusion: The empirical treatment approach of managing bowel symptoms before intervening for bladder dysfunction in children with BBD is found to be appropriate., (©2013 The Author(s)/Acta Paediatrica ©2013 Foundation Acta Paediatrica.)

Unlabelled: Isolated aldosterone synthase deficiency can be the source of life-threatening salt wasting and failure to thrive in infancy. We studied an infant with failure to thrive and persistent hyponatremia despite oral sodium supplementation. Initial analyses revealed highly elevated plasma renin but normal values of plasma aldosterone. The biochemical diagnosis of corticosterone methyl oxidase deficiency type II was established by multisteroid analysis, revealing a pathognomonic pattern with a highly elevated ratio of 18-OH-corticosterone to aldosterone. This reflects an enzymatic defect in the aldosterone synthase that is responsible for the terminal steps in the aldosterone biosynthesis. Molecular genetic analysis supported the diagnosis revealing homozygosity for a pathogenic c.554C>T (p.T185I) variation in exon 3 of the CYP11B2 gene encoding aldosterone synthase. Homozygosity for two other polymorphic variations c.504C>T (p.F168F) and c.518A>G (p.K173R) were identified as well. Treatment with fludrocortisone resulted in catch-up growth. Discontinuation of treatment at the age of 9 years was later possible without any clinical or biochemical deterioration., Conclusions: Isolated deficiency in aldosterone biosynthesis should be considered in neonates and infants with failure to thrive and salt wasting. Normal levels of plasma aldosterone compared with highly elevated levels of plasma renin indicate an impaired aldosterone biosynthesis and suggest the disorder. Recognition of its existence is important as fludrocortisone replacement therapy effectively normalizes sodium balance and growth., (© 2012 The Author(s)/Acta Paediatrica © 2012 Foundation Acta Paediatrica.)

Studies were carried out on 16 healthy male volunteers to investigate whether intravenous administration of the alpha 2-adrenoreceptor antagonist, idazoxan, could affect fasting antroduodenal motility with and without administration of the agonist, clonidine. Contractile activity was recorded using an oral tube with perfused side holes positioned in the stomach and duodenum. Clonidine decreased antral contractile activity, an effect that idazoxan did not restore. Idazoxan alone did not affect antral motility. In the duodenum, clonidine decreased the number of contractions significantly and idazoxan restored them. Idazoxan alone did not increase duodenal motility but clonidine induced phase-III activity within the first 15 min after administration. The observations indicate that regulation of antroduodenal motility is influenced by alpha 2-adrenoreceptor drugs. Idazoxan may have potential as a motility restoring drug, for example, in postoperative ileus.