Lower Urinary Tract Malformations Research Articles

A systematic review of kidney transplantation outcomes in patients with end-stage renal disease due to childhood lower urinary tract malformations.

Patients with lower urinary tract malformations (LUTM) were suspended from kidney transplantation (KT) programs in the past due to various concerns. Consequently, only a limited number of studies have explored this topic at hand. In this study, our objective was to perform a systematic review (SR) to evaluate the current evidence regarding KT outcomes as well as patient survival (PS), postoperative complications and urinary tract infections (UTI) in individuals with childhood LUTM. The search encompassed databases of Web of Science, Medline (via PubMed), and Embase (via Scopus) to identify all studies reporting outcomes on KT for patients with LUTM. The research included articles published in English from January 1995 till September 2023. Of the 2634 yielded articles, 15 met the inclusion criteria, enrolling a total of 284,866 KT patients. There was significantly better 5-year graft survival (GS) in recipients with LUTM compared to the control group (RR, 1.04; 95% CI 1.02-1.06); while GS at 1-year and 10-year, and PS at 1-year, 5-year and 10-year were similar between groups. On the other hand, the postoperative UTI rate was significantly higher in the LUTM group (RR: 4.46; 95% CI 1.89-10.51). However, data on serum creatinine and estimated glomerular filtration rate on follow-up were insufficient. GS and PS rates appear to be similar in patients with childhood LUTM and those with normal lower urinary tract functions. Despite a higher postoperative UTI rate within this patient group, it appears that this has no effect on GS rates.

Renal Transplants Due to Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) Have Better Graft Survival Than Non-CAKUT Controls: Analysis of Over 10,000 Patients

To determine whether graft survival for patients with congenital anomalies of the kidney and urinary tract (CAKUT) is impaired compared to non-CAKUT counterparts. The United States Renal Data System (USRDS) is a national data system that has collected information about end stage renal disease (ESRD) and renal transplantation since 1995. We identified 10,635 first-time renal transplant patients with ESRD attributed to a CAKUT diagnosis transplanted between 1995 and 2018, with follow-up of 7.9 ± 5.8 years. We matched 1:1 with non-CAKUT transplant recipients, using age at transplant, sex, race, year of transplant, and donor-type. We compared renal transplant death-censored graft survival between CAKUT vs non-CAKUT controls, with further stratification for age at transplant and lower urinary tract malformations (LUTM) vs upper urinary tract malformations (UUTM). Graft survival was better in CAKUT patients with a 5-year survival of 83.3% vs 79.3% (P< .001), and CAKUT status infers a hazard ratio of 0.878 for graft failure on multivariable analysis with Cox regression. Favorability of CAKUT status persisted when stratifying for both pediatric (80.3 vs 77.6% P< .001) and adult (84.5 vs 81.4% P< .001) age groups. Looking within the CAKUT population: comparison of LUTM to UUTM yielded no difference, implying that LUTM is not a risk factor for graft failure. Examining pediatric LUTM alone, graft survival was not better than matched non-CAKUT counterparts with 5-year graft survival of 69%-75% for LUTM adolescents. Renal transplant graft survival is better overall in CAKUT patients as opposed to non-CAKUT counterparts. Pediatric LUTM patients have similar graft survival to controls.

Long-term Outcome of Renal Transplantation in Patients with Congenital Lower Urinary Tract Malformations: A Multicenter Study.

Renal insufficiency can occur in patients with congenital lower urinary tract malformations (LUTM) even when managed during infancy. Data in the current literature concerning this subject remain sparse. The aim of this study was to report the feasibility and long-term results of renal transplantation during adulthood in patients with a congenital LUTM. A retrospective multicenter study from 3 French renal transplant centers was conducted, including 123 transplantations on 112 patients with LUTM (1996-2016). Graft survival, patient survival, and complications were analyzed. Results were stratified according to the underlying uropathy and the type of initial management during childhood or before transplantation. In this study, patients suffering from posterior urethral valves (n = 49), spina bifida (n = 21), central neurogenic bladder (n = 13), bladder exstrophy (n = 14), prune belly syndrome (n = 12), Hinman syndrome (n = 6), urogenital sinus (n = 4), and other pathologies (n = 4) were included. The mean age at transplantation was 32.1 years old (±11.2). The mean follow-up period was 7.2 years. Patient survival at 1, 5, 10, and 15 years was 97.4%, 93.0%, 89.4%, and 80.0%, respectively. Graft survival at 1, 5, 10, 15, and 20 years was 96.6%, 87.6%, 77.3%, 60.6%, and 36.4%, respectively. Enterocystoplasty and continent urinary diversions exposed grafts to more frequent acute pyelonephritis (P = 0.02). There was no difference in graft survival when transplantation was performed on an enterocystoplasty or urinary diversions compared with a native bladder, provided a well-conducted bladder management. Even though enterocystoplasty and continent urinary diversions exposed grafts to more frequent acute graft pyelonephritis, patient and graft survival rates in LUTM at 10 years were similar to other kidney transplantations on native bladders.

Pelvic floor dysfunction in the immediate puerperium, and 1 and 3 months after vaginal or cesarean delivery.

To identify and assess postpartum pelvic floor dysfunction (PFD) between vaginal delivery, elective cesarean delivery (ECD), and intrapartum cesarean delivery (ICD). The present prospective observational study included women aged at least 18years with no history of pelvic surgery or lower urinary tract malformation, and who had not undergone pelvic floor muscle (PFM) training in the preceding 12months, who underwent delivery at Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil between August 1, 2016, and May 31, 2017. Participants were assessed at 48hours (phase 1), 1month (phase 2), and 3months (phase 3) after delivery. Assessments included the International Consultation on Incontinence Questionnaire, Short Form (ICIQ-SF); the Jorge-Wexner anal incontinence scale; a self-rated visual analog scale for pelvic pain; the pelvic organ prolapse quantification (POP-Q) system; and a PFM perineometer. A total of 227 women were assessed in phase 1 (141 vaginal deliveries; 28 ICDs; and 58 ECDs), 79 in phase 2, and 41 in phase 3. The ICIQ-SF, Jorge-Wexner scale, visual analog scale, and perineometer measurements did not identify significant differences in relation to the type of delivery (P>0.05). The type of delivery was not associated with differences in the short-term development of postpartum PFD.

Molecular Characterization of the Genital Organizer: Gene Expression Profile of the Mouse Urethral Plate Epithelium

Lower urinary tract malformations are among the most common congenital anomalies in humans. Molecular genetic studies of mouse external genital development have begun to identify mechanisms that pattern the genital tubercle and orchestrate urethral tubulogenesis. The urethral plate epithelium is an endodermal signaling region that has an essential role in external genital development. However, little is known about the molecular identity of this cell population or the genes that regulate its activity. We used microarray analysis to characterize differences in gene expression between urethral plate epithelium and surrounding tissue in mouse genital tubercles. In situ hybridizations were performed to map gene expression patterns and ToppCluster (https://toppcluster.cchmc.org/) was used to analyze gene associations. A total of 84 genes were enriched at least 20-fold in urethral plate epithelium relative to surrounding tissue. The majority of these genes were expressed throughout the urethral plate in males and females at embryonic day 12.5 when the urethral plate is known to signal. Functional analysis using ToppCluster revealed genetic pathways with known functions in other organ systems but unknown roles in external genital development. Additionally, a 3-dimensional molecular atlas of genes enriched in urethral plate epithelium was generated and deposited at the GUDMAP (GenitoUrinary Development Molecular Anatomy Project) website (http://gudmap.org/). We identified dozens of genes previously unknown to be expressed in urethral plate epithelium at a crucial developmental period. It provides a novel panel of genes for analysis in animal models and in humans with external genital anomalies.

Female Bladder Exstrophy: Report of 2 Unique Cases and Review of the Literature

Bladder exstrophy is a rare lower urinary tract malformation that occurs less frequently in women than in men. We report 2 cases of bladder exstrophy occurring in women. One patient was an adult with congenital bladder exstrophy; the patient's bladder wall flap was used to reconstruct the neourethra after the bladder was closed using a conventional procedure. The other patient experienced lower abdominal trauma that led to widespread loss of skin and subcutaneous tissue, exposing the bladder in the lower abdominal wall. In this patient, a pedicled gracilis muscle flap was used to close the abdominal wall after the closure of the bladder. To our knowledge, the first is the fifth reported case of bladder exstrophy in an adult woman and the latter is the first reported case of bladder exstrophy caused by trauma. Both patients showed good outcomes after undergoing surgical treatment.

Non-neurogenic elimination disorders in children

Non-neurogenic elimination disorders cover a wide spectrum of lower urinary tract and bowel dysfunctions, observed in the absence of a neurological background or lower urinary tract malformation. We reviewed conditions responsible for incontinence during bladder filling with normal voiding patterns (such as overactive bladder, giggle incontinence, post-void dribbling), and dysfunctional voiding syndromes. Dysfunctional elimination syndrome usually includes detrusor-sphincter dyscoordination, small-capacity overactive bladder or decompensated large poorly contractile bladder, and large-volume post-micturition residuals, occasionally associated with bowel dysfunction. At the most severe end of the spectrum lies the non-neurogenic neurogenic bladder syndrome, characterized by the association of a severe impairment of the upper urinary tract with a dysfunctional elimination syndrome. It must be emphasized that if the term 'non-neurogenic' relates to the absence of a neurological lesion, it is however conceivable that these conditions actually do have an underlying neurological cause that remains to be identified.

Differential gene expression in the developing mouse ureter

In many instances, kidney dysgenesis results as a secondary consequence to defects in the development of the ureter. Through the use of mouse genetics a number of genes associated with such malformations have been identified, however, the cause of many other abnormalities remain unknown. In order to identify novel genes involved in ureter development we compared gene expression in embryonic day (E) 12.5, E15.5 and postnatal day (P) 75 ureters using the Compugen mouse long oligo microarrays. A total of 248 genes were dynamically upregulated and 208 downregulated between E12.5 and P75. At E12.5, when the mouse ureter is comprised of a simple cuboidal epithelium surrounded by ureteric mesenchyme, genes previously reported to be expressed in the ureteric mesenchyme, foxC1 and foxC2 were upregulated. By E15.5 the epithelial layer develops into urothelium, impermeable to urine, and smooth muscle develops for the peristaltic movement of urine towards the bladder. The development of these two cell types coincided with the upregulation of UPIIIa, RAB27b and PPARγ reported to be expressed in the urothelium, and several muscle genes, Acta1, Tnnt2, Myocd, and Tpm2. In situ hybridization identified several novel genes with spatial expression within the smooth muscle, Acta1; ureteric mesenchyme and smooth muscle, Thbs2 and Col5a2; and urothelium, Kcnj8 and Adh1. This study marks the first known report defining global gene expression of the developing mouse ureter and will provide insight into the molecular mechanisms underlying kidney and lower urinary tract malformations.

Pediatric renal transplantation and the dysfunctional bladder

We retrospectively reviewed our long-term experience with pediatric renal transplantation into a dysfunctional lower urinary tract to evaluate graft survival, function, and special urological complications. Between 1967 and March 2000, a total of 349 renal transplantations were performed in children younger than 18 years. Malformations of the lower urinary tract were the reasons for end-stage renal failure in 66 children (18.6%). The cause of urinary tract disorders included: meningomyelocele connected with neuropathic bladder (n = 4 transplantations); prune belly syndrome (n = 5 transplantations); VATER association (n = 2 transplantations); posterior urethral valves (n = 27 transplantations); and vesico-uretero-renal reflux (n = 28 transplantations). The majority of the patients underwent surgical interventions to preserve renal function or to prepare renal transplantation. The 1- and 5-year graft survival rate was evaluated with special reference to the underlying disease. The 1-year graft survival rate in all children with lower urinary tract malformations was 83.3%, compared with 88% for all children. In those children with vesico-ureteral reflux, it was 92.8% and in the children with Vater association and prune belly syndrome, it was 85.7%. One graft was lost in the children who had neurogenic bladder, so the 1-year graft survival rate was 75%. The worst 1-year graft survival rate was obtained for boys who had posterior urethral valves (1-year graft survival rate: 74%; 5-year graft survival rate: 62.9%). Concerning the 5-year graft survival rate, it was 70% for all children with malformations of the urinary tract. The best rate was obtained for children with reflux in the native kidneys (78.5%), followed by those with VATER association and prune belly syndrome. As an additional child with neurogenic bladder lost his graft, the 5-year graft survival rate was 50%. Pediatric renal transplantation into a dysfunctional bladder can be connected with high urological complication rates which may contribute to worse graft survival. The 1- and 5-year graft survival rate in children with malformations of the lower urinary tract is worse than in children without bladder dysfunction. We regarded a striking difference between graft survival and the urological disorders which led to renal insufficiency. We obtained the worst graft survival rates in children with posterior urethral valves which are usually connected with bladder emptying problems and dysfunctional voiding. Potential pediatric transplant recipients must be classified according to pathophysiological as well as anatomical abnormalities of the urinary tract and all urological problems have to be solved prior to transplantation. At our center, living donors are favored to plan transplantation of these children properly.

The life of the human kidney before birth: its secrets unfold.

Human kidney and lower urinary tract malformations are a major cause of chronic renal failure in young children. Evidence is emerging that at least some of these disorders have a defined genetic basis. This is a rapidly evolving field, with new human mutations and informative animal models described almost monthly. In this review, we provide a background on important animal studies and then address human kidney development, highlighting recent studies where specific genes have been implicated in the pathogenesis of disease.

Pediatric Laparoscopic Nephroureterectomy in Complicated Urinary Tract Anomalies

In as many as 20% of cases, renal anomalies are associated with lower urinary tract malformations. The management of these complicated urinary tract anomalies often requires ablative as well as reconstructive surgery, which traditionally necessitates simultaneous abdominal and pelvic exposure through debilitating wide and/or separate incisions if repair at the same setting is to occur. The authors present two cases of transperitoneal laparoscopic nephroureterectomy (LN) using minimally invasive techniques in the management of complicated urinary tract anomalies. Two children aged 18 months and 12 years, respectively, with urinary tract anomalies (detrusor hypertrophy secondary to posterior urethral valves, and ureterocele, respectively) underwent LN with lower urinary tract reconstructive surgery. The LN was performed through three 5-mm trocar sites, and most tissue and vascular dissection was done with a 5-mm harmonic scalpel. Specimen retrieval and ureterocystoplasty or ureterocelectomy were accomplished through a small suprapubic incision. Patients were studied for safety of surgery, postoperative recovery, resolution of symptoms, and cosmetic results. The LN was performed successfully and safely in each case. Operative times were 89 and 92 min for the LN portion. Recovery was uniformly uneventful, and parenteral analgesics were unnecessary. Both patients were discharged on postoperative day 2 without delayed complications on follow-up visits. Cosmetic results were considered excellent in both cases. The authors advocate LN in the management of complicated urinary tract anomalies requiring nephroureterectomy. Potentially debilitating wide and/or separate incisions required to address these geographically separated anomalies at the same setting via traditional open techniques can thus be avoided.