CDH12 as a Candidate Gene for Kidney Injury in Posterior Urethral Valve Cases:A Genome-wide Association Study Among Patients with Obstructive Uropathies

Background: Posterior urethral valves (PUVs) and ureteropelvic junction obstruction (UPJO) are congenital obstructive uropathies that may impair kidney development. Objective: To identify genetic variants associated with kidney injury in patients with obstructive uropathy. Design, setting, and participants: We included 487 patients born in 1981 or later who underwent pyeloplasty or valve resection before 18 yr of age in the discovery phase, 102 PUV patients in a first replication phase, and 102 in a second replication phase

Total Warm Ischemia and Reperfusion Impairs Flow in All Rat Gut Layers but Increases Leukocyte–Vessel Wall Interactions in the Submucosa Only

OBJECTIVE: To study the effect of warm ischemia and reperfusion (I/R) on local perfusion and leukocyte–vessel wall interactions in vivo in all small bowel layers, and to quantify small bowel tissue injury histologically and by measuring intestinal fatty acid binding protein (I-FABP) release from the enterocytes. SUMMARY BACKGROUND DATA: Gut injury as a result of I/R plays a pivotal role in a variety of clinical conditions, such as small bowel transplantation, heart or aortic surgery, and (septic) shock. The precise mechanism behind I/R injury and the role of microvascular changes remain unclear. The influence of warm I/R of the gut on microvascular parameters in the different gut layers has not been studied before. METHODS: Anesthetized Lewis rats were either subjected to 30 minutes of ischemia and 1 hour of reperfusion or sham-treated as controls. After ligating the inferior mesenteric artery, total warm ischemia was induced by clamping the superior mesenteric artery. Intravital video microscopic measurements were obtained at intervals. Tissue injury of the small bowel and other organs was histologically evaluated afterward. In addition, plasma levels of I-FABP were determined to measure enterocyte damage. RESULTS: After ischemia, mean red blood cell velocity decreased significantly in all layers of the small bowel, but no diameter changes were observed. Leukocyte–vessel wall interactions increased in the submucosa but not in the muscle layers. Plasma levels of I-FABP significantly increased from 30 minutes of reperfusion onward. The intestinal mucosa was severely injured; no histologic damage was detected in other tissues. CONCLUSIONS: This is the first in vivo study showing that total warm ischemia of the rat gut impairs perfusion in the whole small bowel, whereas leukocyte–vessel wall interactions increase in the submucosal layer only. Therefore, the early inflammatory response to I/R seems to be limited to the submucosa. Both microvascular effects may have contributed to the severe morphologic and functional mucosal injury observed after I/R

Clinical and surgical consequences of the COVID-19 pandemic for patients with pediatric urological problems Statement of the EAU guidelines panel for paediatric urology, March 30 2020:Statement of the EAU guidelines panel for paediatric urology, March 30 2020

The COVID-19-pandemic forces hospitals to reorganize into a dual patient flow system. Healthcare professionals are forced to make decisions in patient prioritization throughout specialties. Most pediatric urology pathologies do not require immediate or urgent care, however, delay may compromise future renal function or fertility. Contact with patients and parents, either physical in safe conditions or by (video)telephone must continue. The Paediatric-Urology-Guidelines-panel of the EAU proposes recommendations on prioritization of care. Pediatric-Urology program directors must ensure education, safety and attention for mental health of staff. Upon resumption of care, adequate prioritization must ensure minimal impact on outcome

Compensatory Hypertrophy in Paediatric Patients with a Unilateral Ureteropelvic Junction Obstruction

BACKGROUND: Compensatory hypertrophy is common in children with solitary functioning kidney, but it is unknown whether it also develops in children with unilateral partial reduction of kidney function. OBJECTIVE: The aim of this study was to assess whether children with a unilateral ureteropelvic junction obstruction (UPJO) show compensatory growth of the unaffected kidney. Furthermore, we investigated whether the length of the unaffected kidney was related to the degree of split kidney function lost and other possible risk factors. Lastly, we studied a possible relationship with signs of kidney injury. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively analysed clinical information from 194 children with a unilateral UPJO who participated in the Aetiologic research into Genetic and Occupational/environmental Risk factors for Anomalies in children (AGORA) data- and biobank. Data on kidney length, split kidney function, and other factors possibly associated with kidney length were extracted from electronic patient records. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Pearson’s correlation coefficients between the split kidney function and unaffected kidney length were calculated. Multivariable logistic regression analyses were performed to identify factors associated with kidney length and signs of kidney injury. RESULTS AND LIMITATIONS: Most children with a UPJO had an unaffected kidney length above the reference for age at the end of follow-up (median age 6.5 yr). A correlation with split kidney function was present only in children with a split kidney function of ≥60% in the unaffected kidney (r = 0.41). Aside from split kidney function, UPJO side was the only determinant of kidney length, while no associations between kidney length and kidney injury were identified. CONCLUSIONS: Compensatory growth was visible in most children with a UPJO after sufficient follow-up time and was correlated with split kidney function in children with a severe UPJO. Contralateral kidney length provided no clear prognostic value for developing kidney injury. Studies with more patients and additional biomarkers of kidney injury are needed to further personalise care. PATIENT SUMMARY: Children with obstruction of urine outflow in one kidney often had a larger contralateral kidney. However, the size of this kidney could not be used to predict which children would develop kidney injury

Genome-wide association study in patients with posterior urethral valves

Congenital lower urinary tract obstructions (LUTO) are most often caused by posterior urethral valves (PUV), a male limited anatomical obstruction of the urethra affecting 1 in 4,000 male live births. Little is known about the genetic background of PUV. Here, we report the largest genome-wide association study (GWAS) for PUV in 4 cohorts of patients and controls. The final meta-analysis included 756 patients and 4,823 ethnicity matched controls and comprised 5,754,208 variants that were genotyped or imputed and passed quality control in all 4 cohorts. No genome-wide significant locus was identified, but 33 variants showed suggestive significance (P < 1 x 10(-5)). When considering only loci with multiple variants residing within < 10 kB of each other showing suggestive significance and with the same effect direction in all 4 cohorts, 3 loci comprising a total of 9 variants remained. These loci resided on chromosomes 13, 16, and 20. The present GWAS and meta-analysis is the largest genetic study on PUV performed to date. The fact that no genome-wide significant locus was identified, can be explained by lack of power or may indicate that common variants do not play a major role in the etiology of PUV. Nevertheless, future studies are warranted to replicate and validate the 3 loci that yielded suggestive associations