Outcome of fetuses with lower urinary tract obstruction and normal amniotic fluid volume in second trimester of pregnancy.

OBJECTIVE: Congenital lower urinary tract obstruction (LUTO) is a rare condition with high perinatal mortality and morbidity when associated with severe oligohydramnios or anhydramnios in the second trimester of pregnancy. Severe pulmonary hypoplasia and end-stage renal disease are the underlying causes of poor neonatal outcome in these cases. However, little is known about the subset of fetal LUTO that is associated with a normal volume of amniotic fluid at midgestation. The objective of the current study was to describe the natural history, underlying causes, survival and postnatal renal function outcomes in pregnancies with fetal LUTO and normal amniotic fluid volume during the second trimester of pregnancy. METHODS: This was a retrospective study of all pregnancies with fetal LUTO and normal amniotic fluid volume in the second trimester that received prenatal and postnatal care at our quaternary care institution between 2013 and 2017. Data on demographic characteristics, fetal interventions, perinatal survival, need for neonatal respiratory support, postnatal renal function and need for dialysis at the age of 1 and 24 months were analyzed. RESULTS: Of the 18 fetuses that met the study criteria, 17 (94.4%) survived the perinatal period. Eleven (61.1%) pregnancies developed oligohydramnios in the third trimester, six of which were eligible for and underwent fetal intervention with vesicoamniotic shunt placement, which was performed successfully in all six cases. Two (11.1%) neonates required respiratory support owing to pulmonary hypoplasia. At the age of 2 years, 14 children had follow-up information available, two (14.3%) of whom had normal renal function, eight (57.1%) had developed some degree of chronic kidney disease (Stage 1-4) and four (28.6%) had developed end-stage renal disease (ESRD), including two who had already manifested ESRD in the neonatal period. CONCLUSIONS: Most fetuses diagnosed prenatally with LUTO that is associated with a normal volume of amniotic fluid at midgestation will have a favorable outcome in terms of perinatal survival and few will need long-term respiratory support. However, these children are still at increased risk for chronic renal disease, ESRD and need for renal replacement therapy. Larger multicenter studies are needed to characterize the prenatal factors associated with postnatal renal function, and to investigate the role of fetal intervention in the group of fetuses that present with late-onset oligohydramnios and evidence of preserved fetal renal function. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

A clinical predictive model of chronic kidney disease in children with posterior urethral valves.

BACKGROUND: Posterior urethral valves (PUVs) are associated with severe consequences to the urinary tract and are a common cause of chronic kidney disease (CKD). The aim of this study was to develop clinical predictive model of CKD in a cohort of patients with PUVs. METHODS: In this retrospective cohort study, 173 patients with PUVs were systematically followed up at a single tertiary unit. The primary endpoint was CKD ≥ stage 3. Survival analyses were performed by Cox regression proportional hazard models with time-fixed and time-dependent covariables. RESULTS: Mean follow-up time was 83 months (SD, 70 months). Sixty-five children (37.6%) developed CKD stage ≥ 3. After adjustment by the time-dependent Cox model, baseline creatinine, nadir creatinine, hypertension, and proteinuria remained as predictors of the endpoint. After adjustment by time-fixed model, three variables were predictors of CKD ≥ stage 3: baseline creatinine, nadir creatinine, and proteinuria. The prognostic risk score was divided into three categories: low-risk (69 children, 39.9%), medium-risk (45, 26%), and high-risk (59, 34.1%). The probability of CKD ≥ stage 3 at 10 years age was estimated as 6%, 40%, and 70% for patients assigned to the low-risk, medium-risk, and high-risk groups, respectively (P < 0.001). The main limitation was the preclusion of some relevant variables, especially bladder dysfunction, that might contribute to a more accurate prediction of renal outcome. CONCLUSION: The model accurately predicts the risk of CKD in PUVs patients. This model could be clinically useful in applying timely intervention and in preventing the impairment of renal function.

Antenatal staging of congenital lower urinary tract obstruction.

OBJECTIVE: To propose a staging system for congenital lower urinary tract obstruction (LUTO) capable of predicting the severity of the condition and its prognosis. METHODS: This was a national retrospective study carried out at the eight Academic Hospitals in The Netherlands. We collected prenatal and postnatal data of fetuses at high risk of isolated LUTO that were managed conservatively. Postnatal renal function was assessed by the estimated glomerular filtration rate (eGFR), calculated using the Schwartz formula, considering the length of the infant and the creatinine nadir in the first year after birth. Receiver-operating characteristics (ROC) curve analysis, univariate analysis and multivariate logistic regression analysis with stepwise backward elimination were performed in order to identify the best antenatal predictors of perinatal mortality and postnatal renal function. RESULTS: In total, 261 fetuses suspected of having LUTO and managed conservatively were included in the study. The pregnancy was terminated in 110 cases and perinatal death occurred in 35 cases. Gestational age at appearance of oligohydramnios showed excellent accuracy in predicting the risk of perinatal mortality with an area under the ROC curve of 0.95 (P < 0.001) and an optimal cut-off at 26 weeks' gestation. Fetuses with normal amniotic fluid (AF) volume at 26 weeks' gestation presented with low risk of poor outcome and were therefore defined as cases with mild LUTO. In fetuses referred before the 26th week of gestation, the urinary bladder volume (BV) was the best unique predictor of perinatal mortality. ROC curve analysis identified a BV of 5.4 cm3 and appearance of oligohydramnios at 20 weeks as the best threshold for predicting an adverse outcome. LUTO cases with a BV ≥ 5.4 cm3 or abnormal AF volume before 20 weeks' gestation were defined as severe and those with BV < 5.4 cm3 and normal AF volume at the 20 weeks' scan were defined as moderate. Risk of perinatal mortality significantly increased according to the stage of severity, from mild to moderate to severe stage, from 9% to 26% to 55%, respectively. Similarly, risk of severely impaired renal function increased from 11% to 31% to 44%, for mild, moderate and severe LUTO, respectively. CONCLUSIONS: Gestational age at appearance of oligo- or anhydramnios and BV at diagnosis can accurately predict mortality and morbidity in fetuses with LUTO. Our proposed staging system can triage reliably fetuses with LUTO and predict the severity of the condition and its prognosis. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Variables of initial examination and clinical management associated with survival in small ruminants with obstructive urolithiasis.

BACKGROUND: Obstructive urolithiasis is a common disease associated with a guarded prognosis in small ruminants. HYPOTHESIS/OBJECTIVE: The results of physical examination, laboratory analyses, and clinical management of male small ruminants presented to 2 referral clinics were investigated to identify variables significantly associated with disease outcome, so as to provide better recommendations to animal owners regarding the management of these patients. ANIMALS: Two-hundred ten small ruminants (130 sheep and 80 goats) with confirmed diagnosis of obstructive urolithiasis. METHODS: Clinical findings (including diagnostic imaging) and laboratory results of the 210 animals were reviewed, and relevant information regarding clinical and laboratory variables recorded upon admission and clinical management was retrieved. The association of the different variables with nonsurvival was investigated by univariable and multivariable logistic regression models. RESULTS: Only 39% of all patients considered for treatment and 52% of those undergoing tube cystostomy survived to be released from the clinic. Nonsurvival was strongly associated with a very poor clinical condition upon presentation, obesity, castration, and evidence of uroperitoneum. Among blood variables, abnormal PCV, severely increased serum creatinine concentrations, and increased activity of the creatine kinase were associated with increased risk of nonsurvival. Presence of signs of colic or macroscopic appearance of urine was not significantly associated with outcome. CONCLUSIONS AND CLINICAL IMPORTANCE: The prognosis of obstructive urolithiasis was guarded with survival rates of 39% (overall) to 52% (after tube cystostomy). Intact young males with normal body condition presented early in the course of disease had the best chances of survival.

Effectiveness of vesicoamniotic shunt in fetuses with congenital lower urinary tract obstruction: an updated systematic review and meta-analysis.

OBJECTIVE: To evaluate the effect on perinatal and postnatal survival of vesicoamniotic shunt (VAS) as treatment for fetal lower urinary tract obstruction (LUTO). METHODS: An electronic search of Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews and Scopus using relevant search terms was conducted from inception to June 2015 to identify studies comparing outcomes of VAS vs conservative management for treatment of LUTO. Cohort studies and clinical trials were considered eligible. Single-arm studies and studies that did not report survival were excluded. Sample size and language were not criteria for exclusion. Two reviewers extracted independently data in a standardized form, including study characteristics and results. Primary outcomes were perinatal and postnatal survival. Secondary outcome was postnatal renal function. Data on fetal survival were expressed as odds ratio (OR) and 95% CI. RESULTS: Of the 423 abstracts retrieved, nine studies were eligible for inclusion. These studies included 112 fetuses treated with VAS and 134 that were managed conservatively. There was heterogeneity in study design. Although the data demonstrated a difference in effect estimates between the study arms in terms of perinatal survival (OR, 2.54 (95% CI, 1.14-5.67)), there was no difference in 6-12-month survival (OR, 1.77 (95% CI, 0.25-12.71)) or 2-year survival (OR, 1.81 (95% CI, 0.09-38.03)). In addition, there was no difference in effect on postnatal renal function between fetuses that underwent intervention and those that did not (OR, 2.09 (95% CI, 0.74-5.94)). CONCLUSIONS: Available data seem to support an advantage for perinatal survival in fetuses treated with VAS compared with conservative management. However, 1-2-year survival and outcome of renal function after VAS procedure remain uncertain. Further studies are necessary to evaluate the effectiveness of fetal intervention for LUTO based on different severity of the disease, due to the very low quality of the studies according to GRADE guidelines. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Loss of MeCP2 Causes Urological Dysfunction and Contributes to Death by Kidney Failure in Mouse Models of Rett Syndrome.

Rett Syndrome (RTT) is a neurodevelopmental disorder characterized by loss of acquired skills during development, autonomic dysfunction, and an increased risk for premature lethality. Clinical experience identified a subset of individuals with RTT that present with urological dysfunction including individuals with frequent urinary tract infections, kidney stones, and urine retention requiring frequent catheterization for bladder voiding. To determine if urologic dysfunction is a feature of RTT, we queried the Rett Syndrome Natural History Study, a repository of clinical data from over 1000 individuals with RTT and found multiple instances of urological dysfunction. We then evaluated urological function in a mouse model of RTT and found an abnormal pattern of micturition. Both male and female mice possessing Mecp2 mutations show a decrease in urine output per micturition event. Furthermore, we identified signs of kidney failure secondary to urethral obstruction. Although genetic strain background significantly affects both survival and penetrance of the urethral obstruction phenotype, survival and penetrance of urethral obstruction do not directly correlate. We have identified an additional phenotype caused by loss of MeCP2, urological dysfunction. Furthermore, we urge caution in the interpretation of survival data as an endpoint in preclinical studies, especially where causes of mortality are poorly characterized.

Defining and predicting 'intrauterine fetal renal failure' in congenital lower urinary tract obstruction.

BACKGROUND: The aim of this study was to identify predictors of 'intrauterine fetal renal failure' in fetuses with severe congenital lower urinary tract obstruction (LUTO). METHODS: We undertook a retrospective study of 31 consecutive fetuses with a diagnosis of LUTO in a tertiary Fetal Center between April 2013 and April 2015. Predictors of 'intrauterine fetal renal failure' were evaluated in those infants with severe LUTO who had either a primary composite outcome measure of neonatal death in the first 24 h of life due to severe pulmonary hypoplasia or a need for renal replacement therapy within 7 days of life. The following variables were analyzed: fetal bladder re-expansion 48 h after vesicocentesis, fetal renal ultrasound characteristics, fetal urinary indices, and amniotic fluid volume. RESULTS: Of the 31 fetuses included in the study, eight met the criteria for 'intrauterine fetal renal failure'. All of the latter had composite poor postnatal outcomes based on death within 24 h of life (n = 6) or need for dialysis within 1 week of life (n = 2). The percentage of fetal bladder refilling after vesicocentesis at time of initial evaluation was the only predictor of 'intrauterine fetal renal failure' (cut-off <27 %, area under the time-concentration curve 0.86, 95 % confidence interval 0.68-0.99; p = 0.009). CONCLUSION: We propose the concept of 'intrauterine fetal renal failure' in fetuses with the most severe forms of LUTO. Fetal bladder refilling can be used to reliably predict 'intrauterine fetal renal failure', which is associated with severe pulmonary hypoplasia or the need for dialysis within a few days of life.

Acquired urethral obstruction in New World camelids: 34 cases (1995-2008).

OBJECTIVE: Document the clinical features, short- and long-term outcomes and prognostic factors in New World camelids with acquired urethral obstruction. DESIGN: Retrospective case study. METHODS: Case data from medical records of 34 New World camelids presenting with acquired urethral obstruction were collected and follow-up information on discharged patients was obtained. Associations with short- and long-term survival were evaluated using Wilcoxon rank-sum tests, exact-logistic regressions and Kaplan-Meier survival curves. RESULTS: Of the 34 New World camelids 23 were intact males and 11 were castrated; 4 animals were euthanased upon presentation, 7 were treated medically and 23 surgically, including urethrotomy, bladder marsupialisation, tube cystostomy alone or combined with urethrotomy, urethrostomy or penile reefing. Necrosis of the distal penis was found in 4 animals and all were short-term non-survivors. Short-term survival for surgical cases was 65%, and 57% for medical cases. Incomplete urethral obstruction at admission and surgical treatment were associated with increased odds of short-term survival. Of 14 records available for long-term follow-up, 6 animals were alive and 8 were dead (median follow-up 4.5 years, median survival time 2.5 years). Recurrence of urethral obstruction was associated with long-term non-survival. CONCLUSIONS: Surgically treated New World camelids with incomplete urethral obstruction have the best odds of short-term survival and those with recurrence of urethral obstruction have a poor prognosis for long-term survival.

Short- and long-term outcome after perineal urethrostomy in 86 cats with feline lower urinary tract disease.

BACKGROUND: Perineal urethrostomy is a surgical method for alleviating urethral obstruction in cats with complicated or recurrent obstructive feline lower urinary tract disease. However, long-term outcome of perineal urethrostomy in cats with feline lower urinary tract disease has only been described in studies with relatively few cats. OBJECTIVES: The aim of this study was to evaluate the long-term prognosis, recurrent episodes, quality of life and survival times in cats with feline lower urinary tract disease who underwent perineal urethrostomy. MATERIALS AND METHODS: Data was collected from 86 cats from medical records, including 75 cats with at least 6 months survival, whose owners responded by questionnaire-based telephone interviews. RESULTS: Long-term follow-up ranged from 1·0 to 10·4 years. The median survival time for all cats was 3·5 years after surgery. Forty-seven cats were still alive at the time of the study. Five cats (5·8%) did not survive the first 14 days after perineal urethrostomy surgery; another six cats (7·0%) did not survive 6 months. Seventy-five cats (87%) lived longer than 6 months; 45 (60%) of these were asymptomatic after surgery; 8 of 75 cats (10·7%) experienced severe signs of recurrent feline lower urinary tract disease. For 19 cats, data were available for more than 6 years. Among these, 13 cats were still alive at the time of this study. The six non-surviving cats had all been euthanased for diseases unrelated to the urinary tract. Eighty-eight percent of the owners categorised their cat's long-term quality of life as good. CLINICAL SIGNIFICANCE: This study shows that long-term quality of life after perineal urethrostomy in cats with obstructive feline lower urinary tract disease is good (as assessed by owners) and the recurrence rate is low.

Urethral obstruction in cats: predisposing factors, clinical, clinicopathological characteristics and prognosis.

Feline lower urinary tract diseases in general, and urethral obstruction (UO) in particular, are common clinical conditions in cats. The aims of this study were to identify risk factors for UO, to characterise clinical and clinicopathological signs, outcome and recurrence, as well as risk factors for mortality and recurrence. Eighty-two cats with UO were compared to 82 sex and time matched controls. The mean age of cats with UO was significantly lower compared to controls, while the mean body weight was higher. The proportion of indoors-outdoors cats was significantly lower in the study group compared to the control group, and the proportion of cats consuming only dry food was higher. Overall mortality was 8.5%. Ionised calcium was significantly higher in survivors compared to non-survivors, and the prevalence of hypocalcaemia was lower. Recurrence in 6 months and 2 years were 22% and 24%, respectively. Cats with recurrence had significantly lower urine pH at presentation.

Boys with posterior urethral valves: outcome concerning renal function, bladder function and paternity at ages 31 to 44 years.

PURPOSE: The short-term prognosis for boys with posterior urethral valves (PUV) has improved in recent decades, but the long-term prognosis in terms of renal and bladder function and fertility is still a matter of great concern. This study is a followup of boys with PUV and dilated upper urinary tract treated in 1956 to 1970 at the Children's Hospital in Göteborg, Sweden. MATERIALS AND METHODS: The records of 54 boys treated for PUV were reviewed. Of 27 boys with PUV and upper urinary tract dilation, 5 boys (18%) died at an early age and 3 boys were lost to followup during adolescence, leaving 19 to be included in the followup. They all answered a questionnaire about renal and bladder function and paternity. RESULTS: Of the 19 men 32% were uremic, 21% had moderate renal failure and 47% had not been checked since adolescence. There were signs of bladder dysfunction in 40% and all these subjects had bladder symptoms suggesting detrusor weakness as the cause. All the men were continent. The ability to father children was dependent on whether or not the man was uremic. CONCLUSIONS: This long-term followup study emphasizes the importance of checking renal and bladder function throughout life in men born with PUV. Increasing attention to bladder dysfunction and its early treatment could probably improve the long-term prognosis.

Predictive factors of fetal urethral obstruction: a multivariate analysis.

OBJECTIVE: The purpose of this study was to identify predictive factors of fetal urethral obstruction. METHODS: One hundred and forty-eight children with fetal hydronephrosis were admitted, submitted to a systematic protocol and prospectively followed. Possible predictive factors of urethral obstruction associated with fetal echography and clinical findings on admission were studied. The analysis was conducted in two steps. In a univariate analysis, variables associated with urethral obstruction were identified by the chi(2) test or by Fisher's exact test. Then, the variables that were significantly associated with urethral obstruction were included in a multiple logistic regression analysis. RESULTS: After final adjustment by multiple logistic regression analysis, only two variables were identified as independent predictors of fetal urethral obstruction: oligohydramnios (odds ratio, OR = 5, 95% confidence interval, CI, = 1.3-15, p = 0.01) and megacystis (OR = 9, 95% CI = 2.0-40, p = 0.004). The sensitivity and specificity of the combination of both variables were 60 and 98.5%, respectively. CONCLUSIONS: The presence of oligohydramnios and megacystis on prenatal ultrasound is highly predictive of fetal urethral obstruction.

Management of the fetus with a correctable malformation in Paris maternity units: evolution 1985-1994.

OBJECTIVE: To analyze the evolution of the management of delivery and neonatal care in a population of children with correctable malformations born in Parisian maternity hospitals during the period 1985-1994. METHODS: Data were collected by the Paris Registry of Congenital Anomalies from 400,000 births recorded in Parisian maternity hospitals over a 10-year period. Chromosomal anomalies were excluded. The evolution between the first period (1985-1989) and the second (1990-1994) was analyzed for the following indicators in the management of liveborn children: place of delivery; frequency of prenatal diagnosis; transfer to intensive care units, and mortality. RESULTS: More than 60% of the births of malformed children took place in public maternity hospitals where better management is offered. Most of them were prenatally diagnosed, except for esophageal and anorectal atresia for which the rate of prenatal diagnosis was low. For malformations with poor prognoses (diaphragmatic and abdominal wall anomalies), the rate of deliveries in public maternity hospitals reached about 90%, mostly in those with intensive care units. The evolution between the two periods was characterized by a quicker transfer to intensive care units, during the first day of life for most cases. Lethality during the first day, which was already low during the first period, decreased further. The early neonatal mortality rate decreased for cardiac anomalies, but not significantly. The prognosis remained poor for diaphragmatic anomalies: 49% of liveborn children died during the first week of life.