Assessing safety and tolerability of super selective alpha-1 adrenergic blockers in infants under 3 years: Insights from a single-center study on lower urinary tract obstruction (LUTO).

BACKGROUND: Little is known about alpha blocker use in young children, particularly in those with lower urinary tract obstruction (LUTO). Therefore, we aimed to assess the safety and tolerability of selective alpha-blockers in children under 3 years of age with LUTO. METHODS: A prospectively-collected database captured 93 patients born between 12/2005 and 01/2023. Assessed data included baseline characteristics, ultrasound features, blood pressure (BP), side effects and creatinine values. Primary outcome was side effects or discontinuation of alpha-blockers. Secondary outcomes were BP parameters, growth, and kidney function. Data are shown as median with interquartile range (IQR), Odds Ratio (OR) with 95% CI and mean value with standard deviation (SD). RESULTS: A total of 33 patients less than 3 years of age were started on alpha-blockers at 16.8 ± 11.8 months and followed for 48.9 ± 40.5 months. At last follow-up, no significant effect on systolic/diastolic BP percentiles (p > 0.9 and p > 0.9), creatinine levels (p > 0.9). Weight percentiles increased to the last follow-up (37.8 ± 33.2 vs. 53.6 ± 32.9, p = 0.0133) while height percentiles increased from 28 to 100 days to last follow-up (12.9 ± 18.3 vs. 39.6 ± 35.2, p=0.001). Four patients discontinued alpha-blockers; however, no side-effects were reported during the study period. CONCLUSIONS: No severe clinical or systemic side effects were observed, demonstrating safety and tolerability in young children with LUTO. Although alpha-blockers did not significantly improve kidney function in short term follow-up, and failure to thrive was not observed in these children. Additional studies with more patients are required to assess the optimal dosing and timing leading to maximal benefits for these infants.

Right perirenal urinoma and urinothorax in an infant after neonatal ablation of posterior urethral valve: A rare complication diagnosed by pleural aspiration and treated with perinephric drainage: a case report.

OBJECTIVE: Urinothorax and urinoma are rare complications of obstructive uropathy. They might occur due to persistent high back pressure on the renal parenchyma. Urinothorax usually arises while the obstruction exists; in contrast to our case, the child presented after being operated on. He had falsely high creatinine before the operation, which was later explained by creatinine recirculation. CLINICAL PRESENTATION AND INTERVENTION: We are reporting an uncommon case of late presentation of ruptured urinoma in a 2-month-old Kuwaiti male. It led to urinothorax/uroperitoneum that caused respiratory distress and was associated with creatinine recirculation, requiring retroperitoneal perinephric catheter insertion. The child had recovered and was discharged home. CONCLUSION: A high index of suspicion is required to diagnose urinothorax, especially in patients with a history of obstructive uropathy. Aspiration of the pleural effusion will guide you to reach the diagnosis. Creatinine recirculation is rarely described in the literature. Having a patient with urinothorax/uroperitoneum should raise the suspicion of falsely elevated creatinine levels.

Retrospective evaluation of the prevalence and risk factors associated with red blood cell transfusions in cats with urethral obstruction (2009-2019): 575 cases.

OBJECTIVE: To evaluate the prevalence of red blood cell (RBC) transfusions and factors associated with the need for transfusion in cases of feline urethral obstruction (FUO). Secondarily, to compare survival to discharge in cats receiving an RBC transfusion versus those that did not. DESIGN: Retrospective, multi-institutional study from 2009 to 2019. SETTING: Four university teaching hospitals. ANIMALS: Six hundred twenty-two total occurrences of FUO in 575 cats. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Medical records were retrospectively reviewed for pertinent information. The overall prevalence of severe anemia (PCV < 0.20 L/L [<20%]) at presentation was 1.0% (6/622). The prevalence of RBC transfusions during hospitalization was 2.1% (13/622). Cats that received an RBC transfusion weighed significantly less than those that did not (4.9 vs 5.8 kg; P = 0.034) and had a lower PCV at presentation (0.30 L/L [30%] vs 0.41 L/L [41%]; P < 0.001). Hospitalization time (240 vs 72 h) and indwelling urinary catheter time (168 vs 48 h) were significantly longer in cats receiving a transfusion compared with those that did not (P < 0.001). Creatinine concentrations were not significantly associated with transfusion administration, while BUN was higher in cats receiving a transfusion (15.35 mmol/L [43 mg/dL] vs. 11.78 mmol/L [33 mg/dL]; P = 0.043). Transfusion rates were significantly higher in cats undergoing perineal urethrostomy (5.5%) compared with those that did not undergo surgery (0.97%; P < 0.001). The overall survival to discharge rate was 96%. Cats not receiving an RBC transfusion were significantly more likely to survive to discharge than those that did (odds ratio: 14.7, 95% confidence interval: 1.8-37; P < 0.001). CONCLUSIONS: FUO is rarely associated with severe anemia and the need for RBC transfusions. In this study, cats receiving an RBC transfusion were less likely to survive to discharge; therefore, requiring a blood transfusion may be associated with a worse prognosis. In addition, the need for surgical intervention was associated with a higher prevalence of RBC transfusions.

Advancement of 3D printing technology for the development of a training model in US-guided vesicoamniotic shunting for early LUTO therapy.

INTRODUCTION: Prenatal lower urinary tract obstruction (LUTO) is a rare and challenging condition with potential severe morbidity and mortality. Prenatal shunting methods, specifically vesicoamniotic shunting (VAS) and fetal cystoscopy, aim to manage this condition. However, comprehensive education and training are hindered by the rarity of LUTO. To address this gap, we present a low-cost 3D-printed ultrasound training model for VAS in LUTO fetuses. The aim of the study was to evaluate ultrasound and haptic fidelity of the model. MATERIAL AND METHODS: Ultrasound images of three LUTO fetuses at 12-14 weeks were utilized to create detailed 3D-printed models. Fusion360TM software generated stereo-lithography files, and the Formlabs Form3® printer, using Flexible 80A resin, produced the models. A simulation box mimicking uterine conditions and fetal anatomy was developed for testing. Ultrasound assessments determined model accuracy, and expert evaluations gauged fidelity for VAS placement. RESULTS: The 3D-printed model accurately replicated LUTO fetal anatomy, demonstrating structural integrity and realistic sonographic and haptic feedback during 20 punctures. Macroscopic visualization confirmed the model's durability and authenticity. DISCUSSION: This innovative 3D-printed model addresses the scarcity of LUTO cases and the lack of realistic training tools. Simulation models enhance skills, providing a controlled learning environment that bridges theoretical knowledge and clinical application, potentially improving patient outcomes. CONCLUSIONS: The 3D-printed training model for VAS in LUTO represents a significant advancement in surgical education, offering realistic anatomical simulation and tactile feedback. Future studies should assess its effectiveness in enhancing surgical skills and impacting patient outcomes in clinical practice.

Blood plasma and urinary biomarkers of oxidative stress in cats with urethral obstruction.

BACKGROUND: This study aimed to investigate variations of the oxidative status in cats affected by urethral obstruction (UO) under Feline Idiopathic Cystitis (FIC) and Bacterial Cystitis (BC), in comparison with a group of healthy subjects. In both groups, the levels of several markers (either direct or indirect) indicative of the oxidative attack and of the antioxidant response were analyzed on plasma and urine samples. In particular, the plasma samples were evaluated for nitric oxide (NO), hydroperoxides derived by reactive oxygen activity (d-ROMs test), superoxide anion (O2-), glutathione peroxidase activity (GPx), superoxide dismutase activity (SOD), and ferric reducing antioxidant power (FRAP test); while on urine the levels of NO, d-ROMs, FRAP, SOD, malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) were measured. Urine of UO patients was also subjected to urine-culture test. RESULTS: The analytical data on plasma showed that UO, independently of the FIC or BC etiology, induced the insurgence of oxidative stress conditions at the systemic level. In the urine of the UO patients, except for SOD that increased, the markers of redox status were markedly decreased due probably their compromised filtration, thus suggesting involvement of renal function (assessed also by the high levels of plasma creatinine and proteinuria) with no oxidative damage of the lower urinary tract. Moreover, the adoption of a novel oxidative stress index' (OSI) allowed to establish, by means of a numerical value, the different degrees of oxidative stress conditions for single UO patients, both in terms of oxidative attack and antioxidant response. CONCLUSIONS: Feline urethral obstruction, induced by Idiopathic Cystitis and Bacterial Cystitis, causes oxidative stress conditions at the systemic level that do not interest the lower urinary tract. Despite to the high variability of the profiles of oxidative stress indexes both in healthy and UO patients, the determination of OSI made possible the evaluation of their single degrees of oxidative stress. Possibly the results of this investigation can be compared with those of correspondent pathologies both in humans and in other animal species.

Surgical management of urethral obstruction secondary to perineal liposarcoma in a dog: a case report.

BACKGROUND: Swelling of the perineal region in male dogs is most commonly caused by a perineal hernia. Clinical signs associated with perineal hernia are constipation, tenesmus or stranguria. This case report documents a rare cause of perineal swelling created by the growth of a malignant tumour leading to urethral obstruction and subsequent stranguria. CASE PRESENTATION: An 11-year-old neutered male German Shepherd was presented for swelling in the perineal region and stranguria for three days. Complete blood count and serum biochemistry were unremarkable. Ultrasound revealed a heterogeneous mass in the perineal region. Retrograde urethrography showed a severe narrowing of the urethra caudal to the pelvis. A fine-needle aspirate of the mass was highly suspicious for liposarcoma. Staging was performed by computed tomography (CT) of the thorax and abdomen. Total penile amputation in combination with pubic-ischial pelvic osteotomy, transposition of the remaining urethra through the inguinal canal, V-Y-plasty cranial to the prepuce and preputial urethrostomy were performed to remove the tumour. Histopathology confirmed a well-differentiated liposarcoma with complete histological margins. Six months after the surgery the dog was doing well and there were no signs indicating local tumour recurrence. CONCLUSIONS: Wide surgical excision is generally recommended for soft tissue sarcomas, however this is sometimes not feasible for large tumours. In the case reported here, tumour resection was achieved by a combination of several surgical techniques with a good clinical outcome.

Therapeutic efficacy of 180-W GreenLight laser photoselective vaporization of the prostate for storage symptoms concomitant with benign prostatic obstruction and a search for outcome predictors.

PURPOSE: Benign prostatic obstruction (BPO) is the most common cause of lower urinary tract symptoms among men. GreenLight photoselective vaporization of the prostate (GL-PVP) using a 180-W Xcelerated performance system (XPS) laser is a well-established method for treating BPO-induced voiding symptoms. However, its therapeutic effects on storage symptoms remain unclear. This study aimed to analyze the storage outcomes in patients who underwent 180-W XPS GL-PVP for BPO and to identify outcome predictors. MATERIALS AND METHODS: Patients who underwent 180-W XPS GL-PVP for BPO between May 2018 and May 2021 were retrospectively reviewed. Data on clinical characteristics, prostate volume, preoperative and postoperative International Prostate Symptom Scores (IPSS), and preoperative urodynamic parameters were collected. A favorable storage outcome was defined as ≥50% reduction in the IPSS storage subscore. RESULTS: Ninety-nine male patients were included, with a mean age of 69.4 ± 9.6 years and a baseline prostatic volume of 75.9 ± 33.1 mL. The IPSS total, storage, and voiding subscores significantly decreased after GL-PVP (all p < 0.001). Seventy-two patients achieved favorable storage outcome at 6 months. Multivariate analysis revealed that detrusor underactivity was predictive of unfavorable storage outcomes (p = 0.022), while IPSS voiding-to-storage subscore ratio >1.25 and the presence of detrusor overactivity were predictive of favorable storage outcomes (p = 0.008 and 0.033, respectively). CONCLUSION: 180-W XPS GL-PVP provided excellent outcomes in both voiding and storage lower urinary tract symptoms concomitant with BPO. Preoperative IPSS and multichannel urodynamic parameters including detrusor overactivity and underactivity are valuable predictors of postoperative storage outcomes.

Obstructing urethral membrane in a girl: a rare cause of female bladder outlet obstruction.

Bladder outlet obstruction is known to produce back pressure changes on the urinary tract with devastating sequelae more often than not. Among the causes, posterior urethral valve, which is the most common, is documented to occur exclusively in males. Female posterior urethral valves have been reported in the past in less than 25 cases in existing literature. We discuss the case of a female toddler who presented with symptoms of straining to void and recurrent urinary tract infections. On evaluation, she was found to have an obstructing urethral membrane causing bladder outlet obstruction, which was endoscopically ablated with success.

Effect of tamsulosin on urethral tone in healthy male cats.

OBJECTIVES: Alpha-adrenergic antagonists are commonly used to prevent recurrent urethral obstruction in cats with mixed reports of efficacy. No published data on tamsulosin use in cats are available. The objective of this study was to measure changes in urodynamic parameters and blood pressure in five healthy male cats before and after administration of tamsulosin orally for 4 and 10 days. METHODS: Five young healthy adult male cats from a research colony were administered tamsulosin at 0.1 mg/cat PO q24h for 10 days. Urethral pressure profile and blood pressure measurements were performed before treatment and approximately 6 h after treatment on days 4 and 10. Maximum urethral closure pressure (MUCP) for the prostatic and penile urethra, functional urethral length (FPL), functional area (FA) and systolic blood pressures were recorded and compared between the time points. RESULTS: Significant changes in blood pressure on day 4 (121.1 mmHg ± 20.2 mmHg) and on day 10 (112.6 mmHg ± 14.9 mmHg) compared with day 0 (141.1 mmHg± 33.4 mmHg) were not detected (P = 0.18) in anesthetized cats. No significant difference in MUCP, FA or FPL measurements were detected among baseline, day 4 and day 10 of treatment. Hematuria and transient pollakiuria were induced in two cats with 3.5 Fr urethral catheters. CONCLUSIONS AND RELEVANCE: Tamsulosin at 0.1 mg/cat PO q24h did not induce hypotension in healthy cats. Urodynamic testing performed 6 h after the tamsulosin pill was administered did not detect consistent decreases in urodynamic functions induced by tamsulosin. Repeated catheterization of tom cats with 3.5 Fr catheters may induce significant urethral trauma.

Occurrence of cardiovascular events in 168 cats with acute urinary tract obstruction.

Background: Cardiovascular dysfunction associated with acute kidney injury has been recently described in veterinary medicine, but limited information is available for cats with urinary tract obstruction (UTO). Objective: This retrospective study aimed to describe the type, frequency, timeline, and risk factors for cardiovascular events (CVEs) in cats treated for acute UTO. Animals and procedures: Medical records of cats admitted to the intensive care unit for either upper (ureteral: UUTO) or lower (urethral: LUTO) UTO from 2016 to 2021 were reviewed. Cardiovascular events were defined as development of arrhythmia, heart murmur or gallop sound, clinical signs consistent with fluid overload (CRFO), or decreased tissue perfusion (DTP). Results: One hundred and sixty-eight cats with UTO were recruited (56 with UUTO and 112 with LUTO). Cardiovascular events were reported in 61.9% of cases, including arrhythmia (33.6%), gallop rhythm (28.1%), heart murmur (15.3%), CRFO (14.4%), and DTP (8.6%). Potassium concentration, preexisting chronic kidney disease, and renal pelvic dilation at abdominal ultrasonography were associated with CVE occurrence in multivariate analysis. Conclusions: This study highlighted frequent CVEs in cats treated for UTO, with a potential strong impact on outcome. Therefore, cardiovascular parameters of cats with preexisting chronic kidney disease or those admitted with hyperkalemia or renal pelvic dilation should be closely monitored.

Survenue d'anomalies cardio-vasculaires chez 168 chats présentés pour obstruction du tractus urinaire. Contexte: Si des anomalies cardiovasculaires secondaires à une insuffisance rénale aigue ont été décrites récemment en médecine vétérinaire, ces données restent limitées concernant les obstructions du tractus urinaire (OTU) chez le chat. Objectif: Décrire le type, la fréquence, le délai d'apparition et les facteurs de risques d'anomalies cardio-vasculaires (ACV) chez des chats hospitalisés pour OTU aigue. Animaux et protocoles: Les dossiers médicaux des chats admis en unité de soins intensifs pour obstruction du tractus urinaire haut ( urétérales-OTUH) et bas (urétrales-OTUB) entre 2016 et 2021 ont été consultés. Les ACV retenus étaient des arythmies cardiaques, le développement de souffles cardiaques et de bruits de galop, les signes relatifs à une surcharge en fluide (SRSF) et de diminution de la perfusion tissulaire (SDPT). Résultats: Cent soixante-huit chats avec des OTU ont été recrutés (56 OTUH, 112 OTUB). Des ACV ont été observés dans 61,9 % des cas, incluant des arythmies (33,6 %), l'apparition de bruits de galop (28,1 %) et de souffles cardiaques (15,3 %), des SRSF (14,4 %) et des SDPT (8,6 %). La concentration plasmatique en potassium, la présence d'une MRC sous-jacente et d'une dilatation pyélique à l'échographie abdominale ont été associées à la présence d'ACV par l'analyse multivariée. Conclusions: Cette étude montre que les ACV surviennent fréquemment chez les chats présentés pour OTU, et suggère un impact sur la survie de ces animaux. Les animaux avec un historique de MRC, ceux présentés avec une hyperkaliémie et/ou avec une dilatation pyélique à l'échographie abdominale devraient être surveillés avec plus de précautions que les autres.(Traduit per les auteurs).

Assessment of clinical prognosis improvement in children with concomitant anterior and posterior urethral valves: A case series report.

BACKGROUND: Concomitant anterior urethral valves (AUVs) and posterior urethral valves (PUVs) is an extremely rare congenital urologic anomaly, which may be easily overlooked in the clinic. OBJECTIVE: This study assessed the prognosis of children with concomitant PUVs and AUVs. METHODS: The clinical data of inpatients with concomitant AUVs and PUVs in our hospital were collected from January 1983 to June 2022. The clinical manifestations, auxiliary inspection, and treatment were described in detail. RESULTS: In total, 6 cases of concomitant AUVs and PUVs in boys were found in our hospital, with ages ranging from 3 months to 9 years; the main clinical manifestation was abnormal urination. Four patients exhibited concomitant AUVs and PUVs preoperatively and underwent simultaneous anterior and posterior urethral valvotomy. Follow-up studies showed that 3 patients' clinical symptoms substantially improved with well-maintained renal function. One patient died of renal failure. In the other 2 patients, PUVs were initially identified and excised, but their clinical symptoms did not show substantial improvement. Following voiding cystourethrography (VCUG), the AUVs were found and obstructions were then completely relieved. However, 2 patients died of renal failure. CONCLUSIONS: If urinary symptoms cannot be substantially relieved after posterior urethral valvotomy, VCUG and cystoscopy should be repeated to shorten the interval between anterior and posterior urethral valvotomies to improve patient prognosis.

Fetal biomarkers for lower urinary tract obstruction secondary to posterior urethral valves.

Today, prenatal diagnosis of congenital urogenital malformations is mostly dependent on anatomical variations found on imaging. However, these findings can mislead us in telling us when to intervene, and about post-natal prognosis. Since many findings are dependent on multiple assessments, delayed diagnosis can occur, leading to less optimal outcomes compared to early intervention. Analyses of fetal urinary biomarkers have been proposed as a method of finding biological changes that are predictive for diagnosis and prognosis in fetuses at risk of kidney disease. We interviewed a group of researchers that have demonstrated that by combining multiple omics traits extracted from fetal urine, the biological variability found in single omics data can be circumvented. By analyzing multiple fetal urine peptides and metabolites at single time point, the prognostic power of postnatal renal outcome in fetuses with lower urinary tract obstruction is significantly increased. In this interview, we inquired about the technical aspects of the tests, challenges, and limitations the research group have come across, and how they envision the future for multi-omics fetal analysis in the clinic.

[Minimally invasive treatment of benign prostatic hyperplasia : The German S2e guideline 2023-part 4]. / Minimalinvasive Therapien des benignen Prostatasyndroms : Die deutsche S2e-Leitlinie 2023 ­ Teil 4/4.

BACKGROUND: Lower urinary tract symptoms suggestive for benign prostatic obstruction (LUTS/BPO) are one of the most frequent diseases in men and can have a significant impact on quality of life. Instrumental therapies are common, and many patients seek minimally invasive treatment options. OBJECTIVE: Presentation and evidence-based evaluation of the minimally invasive therapy for benign prostatic syndrome. MATERIALS AND METHODS: Summary and overview of chapters 11-13 on minimally invasive therapies for LUTS/BPO of the current long version of the German S2e guideline. RESULTS: In case of absolute indication for surgery or after unsatisfactory or undesired medical therapy, minimally invasive treatments such as UroLift® (Neotract Inc., Pleasanton, CA, USA), Rezá¿¡m™ (Boston Scientific, Malborough, MA, USA), iTIND™ (Olympus America Inc., Westborough, MA, USA), and prostatic artery embolization (PAE) can be considered. These indirect/delayed ablative therapies offer lower morbidity and the possibility of performing them under local anesthesia, but they are inferior to direct ablative/resective techniques in terms of effectiveness and sustainability. CONCLUSIONS: The updated German S2e guideline summarizes evidence-based recommendations for new minimally invasive therapies for LUTS/BPO, which present alternative treatment options for selected patients.

Difficult catheterization and previous urethral obstruction are associated with lower urinary tract tears in cats with urethral obstruction.

OBJECTIVE: To retrospectively assess the hospital prevalence and risk factors associated with iatrogenic lower urinary tear in cats with urethral obstruction (UO). ANIMALS: 15 client-owned cats diagnosed with concurrent UO and lower urinary tears and year-matched control population of 45 cats diagnosed with UO. METHODS: University teaching hospital records were reviewed for cats presenting with UO between January 2010 and December 2022. Signalment, anatomic location of tear, experience of the individual passing the urinary catheter, difficulty level of catheter passage, history of previous UO, blood work parameters on presentation, presence of visible grit in urine, and survival to discharge were recorded. In addition, prevalence of lower urinary tears in cats presenting with UO was calculated. RESULTS: The prevalence of lower urinary tears was 0.92% in UO cats. Cats with lower urinary tears were significantly less likely to survive to discharge and had a longer period of hospitalization than cats without tears. In addition, cats with tears were more likely to have a history of previous UO and had more difficult urinary catheter passage than cats in the control group. Cats with tears also had a higher Hct than the control UO cats. CLINICAL RELEVANCE: Cats that develop lower urinary tears are more likely to have a history of previous UO and difficult catheter passage. This group of cats is also more likely to have a longer hospitalization period and lower survival to discharge rates.

Modified tube cystostomy technique for management of obstructive urolithiasis in small ruminants: procedure and outcome in 17 sheep and goats.

OBJECTIVE: To describe the surgical technique and clinical outcome of small ruminants treated for obstructive urolithiasis using a modified tube cystostomy (MTC) technique. ANIMALS: 15 goats and 2 sheep treated with an MTC between March 2018 and February 2023. CLINICAL PRESENTATION: Animals were diagnosed with obstructive urolithiasis on the basis of history, physical examination, and ultrasonographic examination. An MTC was performed with sedation and a local block. Postoperative medical management was instituted to help reestablish urethral patency, and Foley catheters were removed after successful urination. RESULTS: Animals were hospitalized an average of 3 nights (range, 0 to 14 nights). Complications included urine spillage in the abdomen and accidental deflation of the Foley balloon. Six animals were euthanized due to poor prognosis or failure to regain urethral patency. Foley catheters were removed an average of 15.7 days postoperatively in animals that regained urethral patency. Long-term (> 1-month) follow-up was available for 8 animals, with an average postoperative survival time of 19.4 months (range, 1 to 58 months). Four animals were lost to long-term follow-up. CLINICAL RELEVANCE: This MTC technique is an effective means of catheterizing the urinary bladder in small ruminants. It can be performed under field conditions and serve as a standalone procedure for providing temporary urine egress. Patient size is limited by the length of the introducer, and an intact, distended urinary bladder and plan for reestablishing urethral patency are important considerations.

Kidney disease progression in pediatric and adult posterior urethral valves (PUV) patients.

BACKGROUND: Posterior urethral valves (PUV) is the most common cause of obstructive uropathy in boys; approximately 15% develop kidney failure by early adulthood. However, rates of kidney function decline are poorly defined in PUV children and adults, as is the impact of potentially modifiable chronic kidney disease (CKD) progression risk factors. METHODS: We conducted a retrospective review of all PUV patients followed at our institution from 1995 to 2018. Inclusion criteria were estimated glomerular filtration rate (eGFR) > 20 ml/min/1.73 m2 after 1 year of age, no dialysis or kidney transplant history, and ≥ 2 yearly serum creatinine values after age 1 year. eGFRs were calculated using creatinine-based estimating formulas for children (CKID U25) or adults (CKD-EPI). The primary outcome was annualized change in eGFR, assessed with linear mixed effects models. We also examined the association of acute kidney injury (AKI), proteinuria, hypertension (HTN), and recurrent febrile urinary tract infections (UTIs) with eGFR decline. RESULTS: Fifty-two PUV patients met the inclusion criteria. Median (interquartile range) eGFR decline was 2.6 (2.1, 3.1) ml/min/1.73 m2/year. Children (n = 35) and adults (n = 17) demonstrated progressive decline. Proteinuria and recurrent UTIs were significantly associated with faster progression; AKI and HTN were also associated but did not reach significance. CONCLUSION: PUV patients show progressive loss of kidney function well into adulthood. Proteinuria and recurrent UTIs are associated with faster progression, suggesting potential modifiable risk factors. This is the first study to report annualized eGFR decline rates in PUV patients, which could help inform the design of clinical trials of CKD therapies.

Post-obstructive diuresis after posterior urethral valve treatment in neonates: a retrospective cohort study.

BACKGROUND: The management of posterior urethral valve (PUV) in neonates requires close monitoring in the intensive care unit because of the risk of post-obstructive diuresis (POD). Our aim was to describe the incidence and factors associated with POD in newborns treated for PUV. METHODS: Retrospective analysis of the medical records of all neonates who underwent surgical intervention for PUV in our neonatal intensive care unit between January 2014 and April 2021. RESULTS: Of the 40 patients included, 15 (37.5%) had POD defined by urine output > 6 ml.kg-1.h-1 during the first 24 h following urinary tract obstruction relief. At prenatal ultrasound examinations, oligohydramnios was more common in the group with POD than in the group without (53.3% vs. 8%, p = 0.002). Preterm birth was more frequent in neonates with POD (66.7% vs. 8%; p < 0.001). Median serum creatinine (212 [137-246] vs. 95 [77-125] µmol.l-1; p < 0.001) and urea (8.5 [5.2-12.2] vs. 4.1 [3.5-4.7] mmol.l-1; p < 0.001) concentrations on the day of obstruction relief were significantly higher in the group with POD than in the group without. After adjustment for prematurity, logistic regression models confirmed correlation between the occurrence of POD and the severity of the consequences of urethral obstruction (i.e., oligohydramnios and serum creatinine levels; ß = 2.90 [0.88; 5.36], p = 0.013 and ß = 0.014 [0.003; 0.031], p = 0.034, respectively). CONCLUSIONS: In neonates, POD is common after the relief of PUV-related obstruction. Our findings may help to identify patients at highest risk. A higher resolution version of the Graphical abstract is available as Supplementary information.

The utility of gene sequencing in identifying an underlying genetic disorder in prenatally suspected lower urinary tract obstruction.

OBJECTIVE: Fetal megacystis generally presents as suspected lower urinary tract obstruction (LUTO), which is associated with severe perinatal morbidity. Genetic etiologies underlying LUTO or a LUTO-like initial presentation are poorly understood. Our objectives are to describe single gene etiologies in fetuses initially ascertained to have suspected LUTO and to elucidate genotype-phenotype correlations. METHODS: A retrospective case series of suspected fetal LUTO positive for a molecular diagnosis was collected from five centers in the Fetal Sequencing Consortium. Demographics, sonograms, genetic testing including variant classification, and delivery outcomes were abstracted. RESULTS: Seven cases of initially prenatally suspected LUTO-positive for a molecular diagnosis were identified. In no case was the final diagnosis established as urethral obstruction that is, LUTO. All variants were classified as likely pathogenic or pathogenic. Smooth muscle deficiencies involving the bladder wall and interfering with bladder emptying were identified in five cases: MYOCD (2), ACTG2 (2), and MYH11 (1). Other genitourinary and/or non-genitourinary malformations were seen in two cases involving KMT2D (1) and BBS10 (1). CONCLUSION: Our series illustrates the value of molecular diagnostics in the workup of fetuses who present with prenatally suspected LUTO but who may have a non-LUTO explanation for their prenatal ultrasound findings.

Pop-off mechanisms as renoprotective mediators in children with posterior urethral valves: A systematic review and meta-analysis.

BACKGROUND: Pop-off mechanisms are potential pressure-relieving mediators in patients diagnosed with posterior urethral valves (PUV). This systematic review aimed to synthesize the existing evidence regarding the protective effect of pop-off mechanisms on renal function in children with PUV. METHODS: We conducted a systematic review of the literature that involved an extensive search in the main databases of the medical bibliography. Three independent reviewers selected the relevant articles. Methodological quality was rated using the Newcastle Ottawa Scale index. We used random meta-analyses to compare different outcomes (serum creatine, Nadir serum creatinine, and Chronic Kidney Disease) between children with PUV and pop-off mechanisms and those with PUV without pop-off mechanisms. RESULTS: 10 studies with data from 896 participants were included in this review. Seven articles reported serum creatinine values for each group and 3 of them found significant differences between groups. The random-effects meta-analysis for serum creatinine showed significant lower mean (diff = -52.88 µmol/L [95 % CI -73.65 to -32.11]) in the group of children with pop-off mechanisms, and the random-effects meta-analysis for Nadir serum creatinine showed a marginally significantly lower mean in the group of children with pop-off mechanisms (diff = -12.00 µmol/L [95 % CI -24.04 to 0.04]). The random-effect meta-analysis for Chronic Kidney Disease resulted in a significant risk reduction for the group of children with pop-off mechanisms (odds ratio = 0.48 [95 % CI 0.23 to 0.98]). CONCLUSIONS: Children with PUV and pop-off mechanisms show better renal function and lower risk of Chronic Kidney Disease than those with PUV without pop-off mechanisms suggesting these mechanisms may act as renoprotective mediators. The high heterogeneity between studies in the assessment of renal function and long-term outcomes calls for a cautious interpretation of these findings. Future studies that stratify by different types of pop-off mechanisms and use standardized metrics, such as Nadir creatinine, are needed.