Søren Hagstrøm

Outcome of a standardized approach to childhood urinary symptoms

To investigate the relevance of enuresis subtyping for selection of treatment modality and for long‐term outcome in a large consecutive patient cohort.

Rectal motility in pediatric constipation

Objectives: Constipation is a common disorder in children, but little is known about its etiology. Rectal impedance planimetry determines segmental rectal cross-sectional area (CSA) and pressure, allowing detailed description of rectal motility. The aim of the present study was to compare rectal motility in healthy and constipated children. Methods: We analyzed data from 10 children (1 girl) with constipation according to the Rome III criteria, mean age 8.8 years (standard deviation ± 1.2), and 10 healthy children (5 girls), mean age 9.9 years (standard deviation ± 1.5). CSA was determined at 3 levels (4, 5.5, and 7 cm from the anal verge). The resting rectal motility was recorded for 30 minutes followed by a distension protocol to assess compliance. Runs of phasic rectal contractions were defined as changes of >10% from baseline CSA and lasting at least 2 minutes. Rectal dimensions were expressed as mean CSA. Results: A low-amplitude contraction pattern (3%–5% of baseline CSA) with a frequency of 6 to 8/minute was present in all of the children. There was significantly more time with phasic rectal contractions in constipated children (median 38%, range [0–100]) compared with healthy children (median 8.8%, range [0–57]) (P < 0.05). The rectal CSA was higher in constipated children (median 1802 mm2 [range 1106–2948]) compared with healthy children (1375 mm2 [range 437–1861]) (P < 0.05), but compliance did not differ (constipated: median 38 mm2/H2O [range 12–86] vs healthy 33 mm2/H2O [range 10–63]) (P = 30). Conclusions: In children with constipation, we found phasic rectal contractions for a significantly longer period compared with healthy children, and their rectum is larger than normal.

High plasma aldosterone is associated with a risk of reversible decreased eGFR in childhood idiopathic nephrotic syndrome

BACKGROUND Oedema formation in nephrotic syndrome (NS) may be associated with volume overload or volume contraction. The present study investigates if plasma aldosterone was related to a clinical course symptomatic of either volume expansion or hypovolaemia. METHODS Twenty patients with NS were included. Blood and urine samples were collected before treatment of NS and at stable remission. Aldosterone and other vasoactive hormones were measured in plasma and the patients were classified based on the aldosterone concentrations. RESULTS Five patients were classified with stimulated aldosterone, mean 611 pg/mL [95% confidence interval (CI): 365-993], 12 with suppressed aldosterone, mean 13 pg/mL (95% CI: 6-26), and 3 with unchanged aldosterone, mean 117 pg/mL (95% CI: 101-135). Patients with high aldosterone were characterized by lower estimated glomerular filtration rate (eGFR) (87 ± 30 versus 142 ± 30, P < 0.01), and increased albuminuria (14 ± 11 versus 6 ± 4 g/L, P = 0.03) compared with the remaining patients. eGFR was normalized rapidly by volume expansion in four of these five patients. CONCLUSIONS Elevated plasma aldosterone during NS may be associated with a risk of temporary reduced eGFR. The normalization of eGFR by volume expansion supports the hypothesis of functional hypovolaemia in some patients. Our data suggest that acute measurement of aldosterone may have implications for the management of oedema.

Novel and recurrent variants in AVPR2 in 19 families with X-linked congenital nephrogenic diabetes insipidus

Congenital nephrogenic diabetes insipidus (CNDI) is characterized by the reduced ability of renal collecting duct cells to reabsorb water in response to the antidiuretic effect of vasopressin. Chronic polyuria and polydipsia are the hallmarks of the disease. Approximately 90% of all patients with CNDI have X-linked inherited disease caused by variants in the arginine vasopressin receptor 2 (AVPR2) gene. We present genetic findings in 34 individuals from 19 kindreds including one or more family members with CNDI. Coding regions of AVPR2 were sequenced bi-directionally. We identified eight novel disease-causing variants in AVPR2, p.Arg68Alafs*124, p.Ser171Arg, p.Gln174Pro, p.Trp200Arg, p.Gly201Cys, p.Gly220Arg, p.Val226Glu, and p.Gln291Pro in nine kindreds. In all three families with more than one affected individual, the novel variants segregated with the disease. We also identified eight recurrent disease-causing variants, p.Val88Met, p.Leu111Valfs*80, p.Arg113Trp, p.Tyr124*, p.Ser167Leu, p.Thr207Asn, p.Arg247Alafs*12, and p.Arg337* in ten kindreds. Our findings contribute to the growing list of AVPR2 variants causing X-linked CNDI.Conclusion: Being a rapid diagnostic tool for CNDI, direct sequencing of AVPR2 should be encouraged in newborns with familial predisposition to CNDI.What is Known:• Disease-causing variants in AVPR2 cause X-linked congenital nephrogenic diabetes insipidus (CNDI).• DNA sequencing of AVPR2 is rapid, facilitates differential diagnosis, early intervention, and genetic diagnosis thus reducing morbidity in CNDI.What is New:• We identified eight novel disease-causing variants in AVPR2: p.Arg68Alafs*124, p.Ser171Arg, p.Gln174Pro, p.Trp200Arg, p.Gly201Cys, p.Gly220Arg, p.Val226Glu, and p.Gln291Pro, thereby adding to the growing list of AVPR2 disease-causing variants and emphasizing the importance of genetic testing in CNDI.