Impact of surgical intervention on progression to end-stage renal disease in patients with posterior urethral valve

Background Posterior urethral valve patients present with varied presentations at any age of life and have significant associated morbidity and require long-term follow-up and care. Methods This was a single-center ambispective cohort study carried out over a period of 2 years. Patient data regarding the symptoms, investigations, interventions, secondary complications were recorded and were followed up regularly during the study till either normalization of their creatinine level which was maintained up to one-year post-fulguration (non-CKD) or progression to end-stage renal disease (ESRD) requiring renal transplant. Various clinical factors were then compared between these groups. Results The age of presentation varies from 6 months antenatal period to a maximum of 34 years. Most common symptom was of lower urinary tract obstruction, followed by recurrent febrile UTI. The interval between disease presentation detection and PU valve fulguration ranged from 6 days to more than 5 years, median duration being 1 month. 85.7% patients had hydroureteronephrosis on initial USG. In VCUG, there was no significant difference found between the presence of reflux and poor renal outcome. Age of presentation greater than 2 years was seen in 52% of patients with CKD compared to only 10% patients in non-CKD group (significant, p value 0.02). Among patients who developed CKD, 60% of patients had PU valve fulguration after one month of disease presentation, while in contrast, among the non-CKD group, 80% of patients had it done within one month of disease presentation. (significant, p value 0.03). Conclusions Late age of presentation, delayed fulguration with high initial creatinine, and failure of serum creatinine to return to normal after one-month post-fulguration are important risk factors in the progression of the disease to ESRD. Symptomatic improvement after interventions does not correlate with progression to ESRD. The number of interventions also does not predict progression to ESRD. Interventions should be chosen wisely on case to restore near-normal physiology and delay progression to ESRD.

Antenatal and postnatal management of posterior urethral valves: where do we stand?

Introduction Posterior urethral valve (PUV) is the leading etiology of lower urinary tract obstruction (LUTO) in boys and is an important cause of end-stage renal disease (ESRD) in children. The aim of this article is to review the current status on antenatal intervention for PUV as well as postnatal medical and surgical management. Main body MEDLINE, EMBASE, Pubmed and Google Scholar search was conducted throughout December 2020 using the keywords: posterior urethral valves, congenital urinary obstruction, antenatal, valve bladder syndrome, medical, anticholinergics, alpha blocker, antibiotics, biofeedback, diversion, augmentation cystoplasty and renal transplantation. Only papers written in English were included. The relevant literature was summarized. Despite advances in antenatal intervention for fetal LUTO, it remains associated with considerable fetal and maternal morbidity. Patient selection criteria for antenatal intervention are greatly debated. Fetal intervention has resulted in improved perinatal survival in properly selected cases, with a questionable benefit to postnatal renal function. There is decent evidence supporting the use of anticholinergics in infants and young children following valve ablation, with less robust evidence advocating alpha blockers, overnight catheter drainage and biofeedback. The role of urinary diversion remains contentious. Optimizing bladder dynamics is crucial for successful renal transplantation outcomes. Conclusion While antenatal intervention has failed to improve renal function outcomes of PUV, patient-centered medical and sometimes surgical interventions can help delay the progression of chronic kidney disease. Lifelong monitoring and management of the associated bladder dysfunction is indispensable even after successful renal transplantation.

Genome-Wide Survey for Microdeletions or -Duplications in 155 Patients with Lower Urinary Tract Obstructions (LUTO)

Lower urinary tract obstruction (LUTO) is, in most cases, caused by anatomical blockage of the bladder outlet. The most common form are posterior urethral valves (PUVs), a male-limited phenotype. Here, we surveyed the genome of 155 LUTO patients to identify disease-causing CNVs. Raw intensity data were collected for CNVs detected in LUTO patients and 4.392 healthy controls using CNVPartition, QuantiSNP and PennCNV. Overlapping CNVs between patients and controls were discarded. Additional filtering implicated CNV frequency in the database of genomic variants, gene content and final visual inspection detecting 37 ultra-rare CNVs. After, prioritization qPCR analysis confirmed 3 microduplications, all detected in PUV patients. One microduplication (5q23.2) occurred de novo in the two remaining microduplications found on chromosome 1p36.21 and 10q23.31. Parental DNA was not available for segregation analysis. All three duplications comprised 11 coding genes: four human specific lncRNA and one microRNA. Three coding genes (FBLIM1, SLC16A12, SNCAIP) and the microRNA MIR107 have previously been shown to be expressed in the developing urinary tract of mouse embryos. We propose that duplications, rare or de novo, contribute to PUV formation, a male-limited phenotype.

Diagnostics of anatomical obstruction of the lower urinary tract using uroflowmetry with a pharmacourodynamic test

Uroflowmetry is an effective, non-invasive method for detecting lower urinary tract obstruction. However, by the nature of the uroflowgram, it is impossible to distinguish between the anatomical and functional obstruction of the urethra. The aim of the study was to develop a screening non-invasive method for the diagnosis of anatomical urethral obstruction using uroflowmetry with a pharmacourodynamic test with selective alpha-1-blocker silodosin. The study involved 235 patients aged 66.2±1.8 years (from 30 to 76 years) with symptoms of the lower urinary tract (LUTS). Uroflowmetry was performed using a “Flow-K” uroflowmeter. Ultrasound examinations of the kidneys, prostate and bladder with determination of residual urine were performed using a HONDA HS-2000 ultrasound machine. All patients underwent a pharmacourodynamic test: repeated uroflowmetry 2.5-3 hours after a single dose of 8 mg of silodosin, taking into account the pharmacodynamics of the drug. During the pharmacourodynamic test, 15 patients with obstructive or obstructive-interrupted uroflowgram had no reaction to silodosin, which was considered a positive test for anatomical (mechanical) urethral obstruction. Аn increase the maximum and average volumetric flow rate of urine during urination by 25-30%, respectively from 9.02±0.24 ml/s up to 11.69±0.32 ml/s and from 5.64±0.21 ml/s to 7.03±0.25 ml/s, were noted in 220 patients with obstructive, obstructive-interrupted obstructive-intermittent or intermittent type of uroflowgram when conducting a pharmacaurodynamic test. Such results were considered negative for anatomical (mechanical) urethral obstruction. They testified to functional obstruction of the urethra, which was subsequently successfully corrected with prescribing selective alpha-1-blockers. Patients with a positive pharmacourodynamic test were prescribed further examination using such methods as ureteroscopy, urethrocystoscopy, retrograde urethrography, to confirm the violation of the patency of the urethra or bladder neck. Urethral stricture was diagnosed in 10 patients, a calculus of the posterior urethra in 2 patients, a median lobe of the prostate gland in 3 patients with BPH. In the presence of obstructive or obstructive-interrupted uroflowgram in patients with LUTS, the pharmacourodynamic test with silodosin can be used as a screening non-invasive test to detect anatomical obstruction of the lower urinary tract.

Obstructive urinary disorders

Both upper and lower urinary tract obstruction are prevalent in the palliative care setting. Although sometimes related to urological conditions, non-urological aetiologies are also seen. Common causes of lower urinary tract obstruction include benign prostatic hyperplasia in men, an underlying neurological condition, and advanced pelvic malignancy. In the acute setting, bladder decompression with a Foley catheter is the easiest and fastest way to resolve the problem. Common causes of upper urinary tract obstruction include nephrolithiasis and advanced malignancy. This chapter will address the evaluation and management of these common clinical issues.

Evaluation of the Fetal Therapy Evidence in Lower Urinary Tract Obstruction: Would an ERAS Guideline Improve Outcomes?

<b><i>Background:</i></b> Pregnancies that are prenatally identified to have fetal anomalies are complex and require expert multidisciplinary care. As many conditions can impact the fetus prenatally and require intervention, an enhanced recovery after surgery (ERAS) for lower urinary tract obstruction (LUTO) is being evaluated to determine the level of evidenced-based data available. <b><i>Problem:</i></b> The percutaneous ultrasound-guided fetal surgery procedure for bladder neck obstruction is the focus for elements of preoperative counseling, intraoperative procedure/risk complications, and postoperative management. <b><i>Methods:</i></b> A quality improvement review Squire 2.0 (2000–2020) was undertaken for the percutaneous LUTO fetal surgery shunting (lower urinary tract obstruction), process and procedure which require 2 process pathways, one to evaluate the fetal candidate and a second to treat. This structured review is focused on identifying the process elements to allow the determination of the number of evidenced-based elements that would allow for audit and measurement of the clinical element variance for comparative feedback to the individual surgical provider or surgery center. <b><i>Interventions:</i></b> Titles and abstracts were screened to identify potentially relevant articles with priority given to meta-analyses, systematic reviews, randomized controlled studies, nonrandomized controlled studies, reviews, and case series. <b><i>Results:</i></b> A series of potential clinical elements for the diagnostic fetal evaluation and for the 3 protocol areas of surgical care for the procedures (pre-, intra-, and postoperative care) are identified using an ERAS-like process. <b><i>Conclusions:</i></b> The identified clinical elements have the potential for ERAS-LUTO fetal therapy guideline. Multidisciplinary collaboration (surgeon, anesthesia, nursing, imaging, and laboratory) is required for ERAS quality improvement in the pre-, intra-, and postoperative processes. Process elements in each of the operative areas can be audited, evaluated, compared, and modified/improved.