Joop van den Hoek

Genes in the Ureteric Budding Pathway: Association Study on Vesico-Ureteral Reflux Patients

Vesico-ureteral reflux (VUR) is the retrograde passage of urine from the bladder to the urinary tract and causes 8.5% of end-stage renal disease in children. It is a complex genetic developmental disorder, in which ectopic embryonal ureteric budding is implicated in the pathogenesis. VUR is part of the spectrum of Congenital Anomalies of the Kidney and Urinary Tract (CAKUT). We performed an extensive association study for primary VUR using a two-stage, case-control design, investigating 44 candidate genes in the ureteric budding pathway in 409 Dutch VUR patients. The 44 genes were selected from the literature and a set of 567 single nucleotide polymorphisms (SNPs) capturing their genetic variation was genotyped in 207 cases and 554 controls. The 14 SNPs with p<0.005 were included in a follow-up study in 202 cases and 892 controls. Of the total cohort, ∼50% showed a clear-cut primary VUR phenotype and ∼25% had both a duplex collecting system and VUR. We also looked for association in these two extreme phenotype groups. None of the SNPs reached a significant p-value. Common genetic variants in four genes (GREM1, EYA1, ROBO2 and UPK3A) show a trend towards association with the development of primary VUR (GREM1, EYA1, ROBO2) or duplex collecting system (EYA1 and UPK3A). SNPs in three genes (TGFB1, GNB3 and VEGFA) have been shown to be associated with VUR in other populations. Only the result of rs1800469 in TGFB1 hinted at association in our study. This is the first extensive study of common variants in the genes of the ureteric budding pathway and the genetic susceptibility to primary VUR.

20 years experience with appendicovesicostomy in paediatric patients: Complications and their re-interventions

To evaluate the long‐term outcome of appendicovesicostomies and to present the frequency and timing of complications needing re‐intervention.

Urotherapy in children with dysfunctional voiding and the responsiveness of two condition-specific questionnaires

We sought to establish the responsiveness of the Dutch Vancouver Symptom Score for Dysfunctional Elimination Syndrome (VSSDES) and Pediatric urinary incontinence Quality of life (PinQ) questionnaires. Secondary, we evaluated the outcome of urotherapy extended for children with dysfunctional voiding (DV).

Neurogenic lower urinary tract dysfunction in the early disease phase of paediatric multiple sclerosis

Neurogenic lower urinary tract dysfunction (LUTD) in multiple sclerosis (MS) is highly prevalent in adults, but has not previously been described in paediatric MS. A total of 24 consecutive children with newly diagnosed MS were prospectively assessed for bladder and bowel problems early after diagnosis. Five of 24 children (21%) showed LUTD during assessment. One of these patients did not report voiding complaints. This high prevalence of LUTD indicates that all recently diagnosed patients with paediatric MS should be evaluated early in their disease and treated for urinary problems in order to prevent potential damage to the upper urinary tract.