Modified unilateral periureteral injection technique in the treatment of patients with high-grade vesicoureteral reflux: A study of primary findings

Objective:Although endoscopic treatment has been used by many pediatric urologists for the treatment of vesicoureteral reflux(VUR),it has no considerable success in high-grade VUR.We aimed to describe the primary outcomes of unilateral periureteral injection technique(PIT),as well as bilateral PIT in high-grade VUR.Methods:In this prospective study,we examined 92 ureters in 45 boys and 40 girls from February 2010 to May 2018.Bilateral PIT and unilateral PIT were applied in 67 and 25 refluxing units,respectively.In the unilateral PIT,the subureteral injection site was only at the 5-or 7-o’clock position.However,in the bilateral PIT,the subureteral injection sites were at 5-and 7-o’clock position.Pre-and post-operative reflux grades were evaluated by voiding cystourethrography 6 months after surgery.Results:Seven patients had bilateral reflux.Overall,75(81.5%)ureters showed Grade IV VUR,while 17(18.5%)had primary Grade V VUR.The mean age of the subjects was 39.2 months.In unilateral PIT ureters,VUR was resolved in 23(92.0%)refluxing units.It was downgraded to Grade III in one ureter(4.0%)and to Grade II in another ureter(4.0%).In addition,in bilateral PIT cases,VUR was resolved in 60(89.6%)ureters;it downgraded to Grades II and III in 3(4.5%)and 4(6.0%)refluxing units,respectively.Conclusion:Unilateral PIT can be highly effective in the treatment of selected ureters of high-grade VUR.However,further studies are needed to confirm our results.

Long term outcomes of Cohen’s cross trigonal reimplantation for primary vesicoureteral reflux in poorly functioning kidney

BACKGROUND Open ureteric reimplantation by cross trigonal technique described by Cohen is considered a common surgical option for correction of vesicoureteral reflux(VUR). There is a lack of evidence in literature though for what happens to such kidneys, in the long run, particularly those which are poorly functioning.AIM To assess the long-term outcomes of ureteric reimplantation in poorly functioning kidneys in children with unilateral primary VUR.METHODS Children with unilateral primary VUR and a relative renal function of less than 35% who underwent open or laparoscopic ureteric reimplantation between January 2005 and January 2017 were included in the study. Patients who had a follow up of less than five years were excluded. Preoperative evaluation consisted of a voiding cystourethrogram and Dimercaptosuccinic acid(DMSA) scan. In the follow-up period, patients underwent a diuretic scan at 6 weeks and 6 months.Follow up ultrasound was done for change in grade of hydronephrosis and retrovesical ureteric diameter. Subsequent follow up was done at 6 monthly intervals with evaluation for proteinuria and hypertension and any recurrent urinary tract infection(UTI). For assessment of cortical function, DMSA was repeated annually for 5 years after surgery. A paired-samples t-test was used to test the mean difference of DMSA between pre-post observations.RESULTS During this period, 36 children underwent ureteric reimplantation for unilateral primary VUR. After excluding those with insufficient follow-up, 31 were included in the analysis. Most of the patients were males(n = 26/31, 83.8%). Patient’s age(mean ± SD, range) was 5.21 ± 3.71, 1-18 years. The grades of VUR were grade Ⅱ(1patient), grade Ⅲ(8 patients), grade Ⅳ(10 patients), and grade Ⅴ(12 patients). The pre and postoperative DMSA was 24.064 ± 12.02 and 24.06 ± 10.93, which was almost the same(statistically equal, paired-samples t-test: P = 0.873). The median(range) follow-up duration was 82(60-120)mo. One patient had persistent reflux after surgery(preoperative: grade Ⅳ, postoperative: grade Ⅲ), and the very same patient developed recurrent UTI. The difference in the preoperative and postoperative DRF was less than 10% in 29 patients. In one patient, the DRF decreased by 17%(22% to 05%) while in another patient, the DRF increased by 12%(25% to 37%) after surgery. None of the patients had an increase in scarring after surgery. 15% of patients were hypertensive before surgery and all of them continued to be hypertensive after surgery while none developed hypertension after surgery. None of the patients had significant proteinuria(> 150 mg/d) during the follow-up period.CONCLUSION Children with unilateral primary VUR and poorly functioning kidney maintain the renal function over the long term in most cases. Hypertension and proteinuria do not progress over time in these patients.

Relationship between Vesicoureteral Reflux and Glomerular Filtration Rate in Children

Vesicoureteral reflux(VUR)is one of the most common urinary tract anomalies in children and causes renal damage and studies focusing on the effect of VUR on renal function are rare.We recruited 35 primary VUR patients with recurrent urinary tract infection(UTI)and 10 non-VUR patients with recurrent UTI.Contrast-enhanced voiding urosonography(ceVUS)was performed for VUR grading,and renal dynamic imaging was used for evaluating glomerular filtration rate(GFR,mL/min).Standardized GFR(sGFR),namely GFR/BSA(mL·min-1·m-2),was calculated based on the body surface area(BSA).Total sGFR(tsGFR,mL·min-1·m-2)was obtained from the sum of sGFR on the left and right sides of all the children.The risk of renal regurgitation was equal in the unilateral reflux group.The sGFR of children with grade Ⅳ(45.74±18.05mL·min-1·m-2)and grade V(49.67±23.63mL·min-1·m-2)reflux was significantly lower than that in children with grade Ⅱ(77.69±22.21 mL·min-1·m-2).The renal function compensation of contralateral non-reflux kidney increased in unilateral reflux group,which was higher than that in the control group and level Ⅱ,Ⅳ and Ⅴ of reflux group respectively.In VUR group of the same grade,sGFR decreased with the age at diagnosis.In unilateral grade V refux group,the tsGFR was lower than that in the unilateral grade I reflux group(133.51±48.21 vs.186.87+53.49mL·min-1·m-2).The patients with VUR of unilateral grade Ⅱ were significantly older than those with VUR of unilateral grades Ⅱ and Ⅳ.This study indicates that severe VUR is significantly associated with decreased renal function.Therefore,VUR should be diagnosed early and managed individually.

Off-label-use of sulfur-hexafluoride in voiding urosonography for diagnosis of vesicoureteral reflux in children:A survey on adverse events

AIM To evaluate the risk profile of sulfur hexafluoride in voiding urosonography(VUS) based on a large cohort of children.METHODS Since 2011 sulfur hexafluoride(SH,SonoV ue?,Bracco,Italy) is the only ultrasound contrast available in the European Union and its use in children has not been approved.Within a 4-year-period,531 children with suspected or proven vesicoureteral reflux(f/m = 478/53; mean age 4.9 years; 1 mo-25.2 years) following parental informed consent underwent VUS with administration of 2.6 ± 1.2 mL SH in a two-center study.A standardizedtelephone survey on adverse events was conducted three days later.RESULTS No acute adverse reactions were observed.The survey revealed subacute,mostly self-limited adverse events in 4.1%(22/531).The majority of observed adverse events(17/22) was not suspected to be caused by an allergic reaction: Five were related to catheter placement,three to reactivated urinary tract infections,five were associated with perineal disinfection before voiding urosonography or perineal dermatitis and four with a common cold.In five patients(0.9%) hints to a potential allergic cause were noted: Perineal urticaria was reported in three interviews and isolated,mild fever in two.These were minor self-limited adverse events with a subacute onset and no hospital admittance was necessary.Ninety-six point two percent of the parents would prefer future VUS examinations with use of SH.CONCLUSION No severe adverse events were observed and indications of self-limited minor allergic reactions related to intravesical administration of SH were reported in less than 1%.

Comparative study of conventional urosonography without contrast enhancement and x-ray voiding cystourethrography for diagnosis of vesicoureteral reflux in children

Background:Vesicoureteral reflux is the most common urinary congenital anomaly in children.Given the risk associated with radiation exposure there has been an increasing need for radiation-free method in the diagnosis and follow-up of the vesicoureteral reflux.The aim of our study is to compare conventional urosonography without contrast enhancement and x-ray voiding cystourethrography.Patients and Methods:Children with recurrent urinary tract infection with suspected vesicoureteral reflux were included to the study.Vesicoureteral reflux is demonstrated and graded by x-ray voiding cystourethrography.DMSA is used for the evaluation of renal scar.Conventional sonographic procedure was performed in all patients.Ureterovesical junction insertion angle was evaluated.The diameter and length of the ureterovesical junction were also measured.Results:268 children enrolled to the study.Vesicoureteral reflux was demonstrated in 62 children by x-ray voiding cystourethrography.Ureterovesical junction insertion angle measurement had a statistically significant relation for right and left vesicoureteral reflux presence(right:r:.646,p:.01 and left:r:.446,p:.01).Diagnosis sensitivity of vesicoureteral reflux with conventional ultrasonography is 95.10%and specificity is 81%(Youden’s index 76.1%)for the cutoff value of the ureterovesical junction insertion angle is 28.6 degrees.Positive predictive value is 87.2%,negative predictive value is 94.73%and diagnostic accuracy is 86.29%with conventional ultrasonography.Conclusions:Measurement of ureterovesical junction insertion angle,length and diameter by conventional urosonography is an easy accessible and cheap technique with high sensitivity and specificity for the diagnosis and followup of the vesicoureteral reflux without exposure to ionizing radiation.

Hereditary Vesicoureteral Reflux: A Study of 66 Families

Purpose: We studied the inheritance pattern, clinical features and outcome in children with vesicoureteral reflux (VUR). Characteristics of known familial VUR cases were also compared with those of sporadic VUR. Material and Methods: 726 patients were treated for VUR between 1990-2004. The families were contacted by letter inquiring if other members of the family were affected. The phenotype of all cases (familial and non-familial) was characterized in terms of presenting symptoms, reflux grade, recurrent urinary tract infections, kidney damage, and the natural course of reflux. Results: The response rate was 79%. A total of 99 individuals (22%) reported relatives with VUR. Since some of the 99 index cases belonged to the same family, the total number of families was ultimately 66. The distribution of relatives with VUR was: 38 siblings, 20 parents (15 mothers), 19 cousins, 15 aunts/uncles and 12 grandparents. The phenotype of VUR did not differ between familial and non-familial cases. However, VUR among relatives was of milder grade than index and sporadic cases. Conclusions: The proportion of hereditary reflux in our material was lower than in other studies (22%). We found a strong overrepresentation of maternal transmission of reflux. Severity of the disease did not differ between familial and non-familial VUR.

An evaluation of ureteral diameter ratio and vesicoureteral reflux index in the treatment of primary vesicoureteral reflux

Objective:Vesicoureteral reflux(VUR)index is a simple,validated tool that reliably predicts significant improvement and spontaneous resolution of primary reflux in children.The aim of this study was to evaluate and compare the ureter diameter ratio(UDR)and VUR index(VURx)of patients treated with endoscopic injection(EI)and ureteroneocystostomy(UNC)methods in the pediatric age group due to primary VUR.Methods:Patients under the age of 18 years old who underwent EI and UNC with the diagnosis of primary VUR between January 2011 and September 2021 were determined as the participants.The UDR was assessed using voiding cystourethrography,and the VURx score was determined prior to treatment based on hospital records included in the study.Results:A total of 255 patients,60(23.5%)boys and 195(76.5%)girls,with a mean age of 76.5(range 13.0e204.0)months,were included in the study.EI was applied to 130(51.0%)patients and UNC was applied to 125(49.0%)patients due to primary VUR.The optimum cut-off for the distal UDR was obtained as 0.17 with sensitivity and specificity of 73.0%and 63.0%,respectively.The positive and negative predictive values were 66.0%and 70.0%,respectively.Conclusion:When the UDR and VURx score are evaluated together for the surgical treatment of primary VUR in the pediatric age group,it is thought that it may be useful in predicting the clinical course of the disease and evaluating surgical treatment options.

Responsible genes in children with primary vesicoureteral reflux: findings from the Chinese Children Genetic Kidney Disease Database

Background Primary vesicoureteral reflux(VUR)is a common congenital anomaly of the kidney and urinary tract(CAKUT)in childhood.The present study identified the possible genetic contributions to primary VUR in children.Methods Patients with primary VUR were enrolled and analysed based on a national multi-center registration network(Chinese Children Genetic Kidney Disease Database,CCGKDD)that covered 23 different provinces/regions in China from 2014 to 2019.Genetic causes were sought using whole-exome sequencing(WES)or targeted-exome sequencing.Results A total of 379 unrelated patients(male:female 219:160)with primary VUR were recruited.Sixty-four(16.9%)children had extrarenal manifestations,and 165(43.5%)patients showed the coexistence of other CAKUT phenotypes.Eighty-eight patient(23.2%)exhibited impaired renal function at their last visit,and 18 of them(20.5%)developed ESRD at the median age of 7.0(IQR 0.9–11.4)years.A monogenic cause was identified in 28 patients(7.39%).These genes included PAX2(n=4),TNXB(n=3),GATA3(n=3),SLIT2(n=3),ROBO2(n=2),TBX18(n=2),and the other 11 genes(one gene for each patient).There was a significant difference in the rate of gene mutations between patients with or without extrarenal complications(14.1%vs.6%,P=0.035).The frequency of genetic abnormality was not statistically significant based on the coexistence of another CAKUT(9.6%vs.5.6%,P=0.139,Chi-square test)and the grade of reflux(9.4%vs.6.7%,P=0.429).Kaplan–Meier survival curve showed that the presence of genetic mutations did affect renal survival(Log-rank test,P=0.01).PAX2 mutation carriers(HR 5.1,95%CI 1.3–20.0;P=0.02)and TNXB mutation carriers(HR 20.3,95%CI 2.4–168.7;P=0.01)were associated with increased risk of progression to ESRD.Conclusions PAX2,TNXB,GATA3 and SLIT2 were the main underlying monogenic causes and accounted for up to 46.4%of monogenic VUR.Extrarenal complications and renal function were significantly related to the findings of genetic factors in children with primary VUR.Like other types of CAKUT,several genes may be responsible for isolated VUR.

Diagnosis and management of ureteral complications following renal transplantation

When compared with maintenance dialysis,renal transplantation affords patients with end-stage renal disease better long-term survival and a better quality of life.Approximately 9% of patients will develop a major urologic complication following kidney transplantation.Ureteral complications are most common and include obstruction(intrinsic and extrinsic),urine leak and vesicoureteral reflux.Ureterovesical anastomotic strictures result from technical error or ureteral ischemia.Balloon dilation or endoureterotomy may be considered for short,low-grade strictures,but open reconstruction is associated with higher success rates.Urine leak usually occurs in the early postoperative period.Nearly 60% of patients can be successfully managed with a pelvic drain and urinary decompression(nephrostomy tube,ureteral stent,and indwelling bladder catheter).Proximal,large-volume,or leaks that persist despite urinary diversion,require open repair.Vesicoureteral reflux is common following transplantation.Patients with recurrent pyelonephritis despite antimicrobial prophylaxis require surgical treatment.Deflux injection may be considered in recipients with low-grade disease.Grade IV and V reflux are best managed with open reconstruction.

Augmentation cystoplasty in children with stages III and IV chronic kidney disease secondary to neurogenic bladder

Objective:This study examines the outcome of augmentation cystoplasty(AC)in children with stages III and IV chronic kidney disease(CKD)secondary to neurogenic bladder in which transplantation was not imminent.Methods:Hospital records of all children with CKD stages III and IV who underwent AC between 2008 and 2017 were retrieved to study outcome and complications including estimated glomerular filtration rate(eGFR,National Kidney Foundation Calculator),somatic growth(percentiles,compared with population data),and febrile urinary tract infections(fUTIs)requiring admission.Statistical analysis was performed using R.Results:AC was performed in 13 children with CKD stages III and IV(10 girls;median 8.0 years)with median follow-up of 51 months.Patients had incontinence(10/13),reflux(7/13),and hydronephrosis(13/13)despite antimuscarinics and intermittent catheterization.Bladder capacity was 74%of expected and median compliance was 5 mL/cm H20(inter-quartile range 4 mL/cm H20).All underwent ileocystoplasty(25 cm bowel).One each had nephrectomy and mitrofanoff conduit.All had resolution of incontinence.One had acute kidney injury that recovered.Initial eGFR at presentation(24 mL/min/1.73 m2)improved with conservative management alone(52 mL/min/1.73 m2,p=0.004).This improved further 1 year following AC(61 mL/min/1.73 m2,p=0.036)with stable function at 7 years.There was improvement in somatic growth,hydronephrosis,and fUTI despite no ureteric re-implantation.Conclusion:AC carries acceptable morbidity in children with CKD stages III and IV secondary to neurogenic bladder.Surgery is effective with improvements in continence,eGFR,somatic growth,and propensity for fUTIs.Ureteric re-implantation might not be necessary.