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- Rieke, Johanna Magdalena, et al.
(författare)
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SLC20A1Is Involved in Urinary Tract and Urorectal Development
- 2020
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Ingår i: Frontiers in Cell and Developmental Biology. - : FRONTIERS MEDIA SA. - 2296-634X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies in developingXenopusand zebrafish reported that the phosphate transporterslc20a1ais expressed in pronephric kidneys. The recent identification ofSLC20A1as a monoallelic candidate gene for cloacal exstrophy further suggests its involvement in the urinary tract and urorectal development. However, little is known of the functional role ofSLC20A1in urinary tract development. Here, we investigated this using morpholino oligonucleotide knockdown of the zebrafish orthologslc20a1a. This caused kidney cysts and malformations of the cloaca. Moreover, in morphants we demonstrated dysfunctional voiding and hindgut opening defects mimicking imperforate anus in human cloacal exstrophy. Furthermore, we performed immunohistochemistry of an unaffected 6-week-old human embryo and detectedSLC20A1in the urinary tract and the abdominal midline, structures implicated in the pathogenesis of cloacal exstrophy. Additionally, we resequencedSLC20A1in 690 individuals with bladder exstrophy-epispadias complex (BEEC) including 84 individuals with cloacal exstrophy. We identified two additional monoallelicde novovariants. One was identified in a case-parent trio with classic bladder exstrophy, and one additional novelde novovariant was detected in an affected mother who transmitted this variant to her affected son. To study the potential cellular impact ofSLC20A1variants, we expressed them in HEK293 cells. Here, phosphate transport was not compromised, suggesting that it is not a disease mechanism. However, there was a tendency for lower levels of cleaved caspase-3, perhaps implicating apoptosis pathways in the disease. Our results suggestSLC20A1is involved in urinary tract and urorectal development and implicateSLC20A1as a disease-gene for BEEC.
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| 2. |
- Stenbäck, Anders, et al.
(författare)
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Proprietary non-animal stabilized hyaluronic acid/dextranomer gel (NASHA/Dx) for endoscopic treatment of grade IV vesicoureteral reflux : Longterm observational study
- 2020
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Ingår i: Journal of Pediatric Urology. - : ELSEVIER SCI LTD. - 1477-5131 .- 1873-4898. ; 16:3
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Tidskriftsartikel (refereegranskat)abstract
- Background Since 1993, children aged >1 year with persistent grade III-V vesicoureteral reflux (VUR) and febrile urinary tract infections (UTIs) attending Uppsala University Hospital have undergone endoscopic injection with proprietary non-animal stabilized hyaluronic acid/dextranomer gel (NASHA/Dx; Deflux (R)). Objective Investigate long-term incidence of UTI, bladder dysfunction, ureteral reimplantation and overall clinical findings following endoscopic injection of NASHA/Dx. Study design Children with grade IV VUR diagnosed by voiding cystourethrogram (VCUG) and dilating VUR persisting for >1 year were included in this study. 15-25 years after endoscopic treatment, patients' hospital charts were studied. Information on bladder function and UTIs was obtained via questionnaire, 8-18 years after endoscopic treatment. Results 185 patients (69 boys, 116 girls) were included in the study; 237 grade IV VUR ureters were treated. All study patients were diagnosed with VUR after a febrile UTI (i.e. pyelonephritis). According to the last voiding cystourethrogram, 69% of ureters showed a positive response (VUR grade 0-I), 7% had VUR grade II and 23% had VUR grade >= III. 46 patients (25%) required ureteral reimplantation during follow-up. Among patients treated during the second 5-year period compared with the first (1998-2003 versus 1993-1998), there was a significant decrease in the rate of ureteral reimplantation (31% vs 16%; p = 0.0365). This difference may be attributable to developments over time in the injection technique. UTIs occurred in 30 patients (21% of the evaluable population): 28 females and 2 males. Febrile UTIs were reported in 14 patients (10%), all females. Forty-nine patients (34%) had bladder problems (e.g. underactivity, overactivity, incontinence). Five patients underwent ureteral reimplantation 'late', 6-10 years after the last endoscopic injection. In one male patient, calcification around the NASHA/Dx implantation site was observed during routine examination 2 years after endoscopic treatment; no intervention was required. No safety issues were observed in the remaining 97% of the study population. Conclusions This study represents the longest published followu-p of Grade IV VUR patients undergoing endoscopic treatment. Three-quarters of patients did not need ureteral reimplantation. Optimal injection technique and higher injection volume were associated with a reduced ureteral reimplantation rate. Treatment with NASHA/Dx was durable and well tolerated: long-term risks of UTI, bladder dysfunction and recurrent VUR were low. [GRAPHICS] .
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