Posterior urethral valves and the risk of neurodevelopmental disorders in two FINNISH cohorts.

BACKGROUND: The Posterior Urethral Valve (PUV) is a persistent membrane of the urethra, which causes obstruction in the urogenital tract in boys. To our knowledge, no comprehensive reports have been published on whether PUV is associated to neurodevelopmental disorders. Here, we analyzed a cohort of PUV patients for neurodevelopmental disorders and verified findings in an older cohort. METHODS: In a register based study, we reviewed the hospital registries for patients treated for PUV during 1992-2013 to identify those with neurodevelopmental disorders. Primary outcome measure was any neurodevelopmental diagnosis. Secondary outcome measures were specific disorders: ASD; ADHD, intellectual disability, learning disabilities. Birth weight and gestational age were recorded, serum creatinine levels at specific timepoints were noted. We then investigated these variables to see any correlations to neurodevelopmental disorders. We replicated the strategy for verification in an older cohort of PUV-patients, who had been treated in our institute during 1970-1991. RESULTS: We identified 87 patients treated for PUV of which thirteen (15%) had a verified diagnosis of a neurodevelopmental disorder. 2.3% of PUV patients fulfilled criteria of mild intellectual disability (F70.0/F79.0), 9% had ADHD/ADD-spectrum diagnoses (F90.0/F90.9) and 2.3% had learning disabilities (F83/F81.3). 5.7% of patients presented with difficulties in social interactions (F93.89, F94.8). Five patients presented with more than one neurodevelopmental diagnosis. We confirmed these findings in the older cohort of patients, where a verified neurodevelopmental diagnosis was detected in 14% of patients. We identified no statistically significant associations to gestational age, birth weight or creatinine levels of PUV-patients with neurodevelopmental diagnoses as compared to the PUV-patients not diagnosed for neurodevelopmental disorders. Intellectual disability/mental retardation was more prevalent in our material and this association was statistically significant. DISCUSSION: We show, that the prevalence of intellectual disability among PUV patients exceeds the cumulative prevalence in Finland in both cohorts analyzed here. 15% of PUV-patients presented with a diagnosis of a neurodevelopmental disorder. To our knowledge, this is the first study attempting to outline neurodevelopmental disorders among boys with PUV. This study has limitations. It is register based and only diagnoses made at an institute within our hospital district are considered. The PUV-patients may be under closer surveillance than age-matched healthy children, which may lead to an overrepresentation of cases. The patient number is small and the small subsets of patients within each cohort hamper any further statistical analysis. The neurodevelopmental impacts of pediatric general anesthesia remain elusive and may have corollaries which must be kept in mind when interpretating our results. Patients with PUV require close follow-up in a multi-disciplinary manner, not forgetting neurodevelopmental aspects. Attention to intellectual disability is mandatory. Any suspicion of a developmental delay in a patient with PUV warrants further investigation and corresponding interventions.

Association of Renal Glomerular and Tubular Function With Renal Outcome in Patients With Posterior Urethral Valves.

OBJECTIVE: To analyze renal glomerular and tubular function and their association in patients operated for posterior urethral valves and to prognosticate the risk for end-stage kidney disease (ESKD) METHODS: Sixty-three previously treated patients were evaluated for renal function during 1987-1991. The patients' age at evaluation was 11 years (range 2-24). Glomerular function was assessed by measuring glomerular filtration rate (GFR) and urine albumin excretion. Tubular function was determined by measuring urine concentration capacity and excretion of electrolytes (Na, K, Cl, Ca, P, Mg) and ß-2-microglobulin. Additionally, the prevalence of hypertension and serum parathyroid hormone and aldosterone values were registered. Tubular function was compared with GFR and the risk of developing ESKD before November 2018. RESULTS: Twenty of the study patients (32%) had decreased GFR. In addition, 19% had proteinuria and 56% were hypertensive. Those without proteinuria or hypertension had better GFR values (P < .01 for both). There was a significant correlation between GFR and all the tubular function (P < .05) variables (except excretion of chloride) measured. Compared to the patients with favorable renal outcome, the patients (n = 10) who later developed ESKD had significantly (P < .01) lower GFR and reduced urinary excretion of all measured electrolytes except calcium. Consistently, urine ß-2 microglobulin and serum parathyroid hormone and aldosterone values were significantly higher in the patients who developed ESKD (P ≤ .01). CONCLUSION: Both glomerular and tubular function decline was common and several parameters were likely to predict ESKD in posterior urethral valves patients.

No single reason behind adult lower urinary tract symptoms in patients with posterior urethral valves.

Objective: To analyze which factors in the history of a posterior urethral valve (PUV) patient relate to lower urinary tract symptoms (LUTS) in adulthood. This study also aimed to evaluate whether the patients have developed signs of a myogenic failure of detrusor. Materials and methods: LUTS were evaluated with a DAN-PSS questionnaire in 78 adult patients treated for PUV in childhood. Symptom scores (SS) were compared with patient characteristics and types of treatment. The results of uroflowmetry and post-voiding residual (PVR) measurements were collected from their latest visit to Helsinki University Children's Hospital. Results: The median total symptom score (TSS) was 1 (IQR = 0-5, range = 0-18). The patient age during the investigation and SS were associated (R = 0.220, p = 0.032), but the primary creatinine level and SS were not (R = 0.260, p = 0.081). The median age for achieving continence was 6.3 years. The SS and the age when becoming continent were not associated (p = 0.365 and p = 0.679, respectively). In the age group of 39 years or more, 19 patients with a previous bladder neck incision (BNI) had a higher storage-SS than 15 patients without any previous bladder neck incision (1 (IQR = 0-5) vs 0 (IQR = 0-0), p = 0.030). According to symptoms and post-voiding residual measurements, myogenic failure in adults seems to be rare. Conclusions: LUTS are common, but severe symptoms referring to myogenic failure are rare in men treated for PUV in childhood. The specific reasons for LUTS are difficult to indicate and even the sickest children do not necessarily have LUTS in adulthood.

Controlled Outcomes for Achievement of Urinary Continence among Boys Treated for Posterior Urethral Valves.

PURPOSE: We evaluated the age at which boys with a history of posterior urethral valves after no or minimal anticholinergic medication achieve urinary continence and the factors contributing to continence. MATERIALS AND METHODS: We reviewed the hospital records of all males treated for posterior urethral valves at a single institution between 1990 and 2008. Continence was considered to have been attained if no weekly wetting episodes occurred. We evaluated the influence of patient characteristics, including reduced kidney function and primary ring type ureteral stoma, on age at which continence was achieved. RESULTS: A total of 76 patients were assessed. Achievement of daytime and nighttime urinary continence was markedly delayed in patients (mean ± SD age 5.5 ± 3.3 years and 5.4 ± 3.0 years, respectively) compared to the reference population (2.3 ± 0.5 and 2.9 ± 1.2, p <0.001). Increased serum creatinine levels at age 5 years were associated with later daytime and nighttime continence (mean ± SD 6.0 ± 3.2 and 5.5 ± 2.6 years, respectively, vs 4.1 ± 2.3 and 3.7 ± 1.4 years, respectively, in patients with normal serum creatinine, p ≤0.05). Prenatal or neonatal diagnosis of posterior urethral valves was associated with significantly delayed achievement of daytime continence compared to cases diagnosed later (mean ± SD 5.9 ± 3.6 vs 4.1 ± 1.8 years, p = 0.02). Patients with high nadir serum creatinine and vesicoureteral reflux initially also were at increased risk for urinary tract infections (p = 0.003 and p <0.001, respectively). CONCLUSIONS: Patients with posterior urethral valves achieve daytime and nighttime urinary continence significantly later than their healthy peers. Prenatal or neonatal diagnosis and high serum creatinine are associated with later attainment of continence.

The impact of posterior urethral valves on adult quality of life.

OBJECTIVE: To investigate the quality of life of men who had been treated for posterior urethral valves (PUV) in childhood. PATIENTS AND METHODS: Questionnaires were mailed to 108 patients with PUV treated at the Children's Hospital, University of Helsinki, and 67 (62%) of them responded. Three different questionnaires (15D, LSS, and RAND) were used to evaluate the quality of life. RESULTS: The total quality of life in PUV patients was reported as good compared to the general population in the RAND and LSS surveys. However, in the 15D analysis the PUV patients reported lower scores in sleeping, eating, and sexual activity. Those PUV patients who had been treated for renal insufficiency reported lower scores in several dimensions in all three surveys. Patients with urinary incontinence reported more sleeping problems and regarded themselves physically more disabled. CONCLUSIONS: The PUV patients with renal insufficiency or urinary incontinence had impaired quality of life in several dimensions.

Effects of posterior urethral valves on long-term bladder and sexual function.

Bladder function is often compromised in juvenile patients with posterior urethral valves (PUV). In infancy, such abnormal bladder function is characterized by low compliance or overactivity, but later in life the bladder tends to become oversized and empties poorly. Polyuria, which is often associated with renal failure as well as secondary changes in the bladder neck, also has an effect on bladder function. Perhaps as a consequence of these contributing factors, toilet training is often delayed in children with PUV. Adults who were treated for PUV as a child tend to experience lower urinary tract symptoms at a rate twofold to threefold higher than healthy men. Furthermore, these adult patients with PUV might have risk factors for sexual and fertility dysfunctions later in life, such as cryptorchidism, renal failure and abnormal posterior urethra. However, despite the high incidence of these risk factors, sexual function and fertility seems to be normal in most patients.

Posterior urethral valves and adult sexual function.

OBJECTIVES: To evaluate sexual function and fertility in adult patients treated for posterior urethral valves (PUV) in childhood and to compare these patients with the normal population. To examine if patient characteristics such as chronic renal failure (CRF), history of cryptorchidism and bladder neck incision in childhood have an impact on sexual function. PATIENTS AND METHODS: Information on sexual function was assessed using questions from the International Index of Erectile Function (IIEF). In addition, the patients were asked if they had had children or been treated for CRF. Out of 108 adult patients with PUV, 67 (62%) returned the questionnaires. Sexual function in these patients was compared with 201 controls and paternity rates were compared with a national database. RESULTS: The mean (sd) age of the patients and controls was 38 (9) and 38 (7) years, respectively. Six percent of the patients and 9% of the controls reported problems in achieving erection during sexual stimulation and 9% of the patients and 10% of the controls reported problems with the hardness of erection (P = nonsignificant). Ejaculation was absent in 1/61 sexually active patients (2%). The only significant risk factor in patients for erectile dysfunction (ED) was increasing age. Thirty-three (49%) of all 67 patients and four (57%) of the seven patients with kidney transplantation had had children. The paternity rates were similar to those in corresponding age groups of the general Finnish population. Eight patients (12%) had attempted to have children without success. CONCLUSIONS: Men treated for PUV have a similar prevalence of ED and similar paternity rates to men without PUV. Erectile function and paternity rates can be satisfactory in spite of CRF.

Long-term risk of end stage renal disease in patients with posterior urethral valves.

PURPOSE: Congenital obstructive uropathy can lead to end stage renal disease. Progression to end stage renal disease in childhood is well described but long-term prognosis in adulthood has not been thoroughly investigated. In this study we evaluated the risk of end stage renal disease in patients with posterior urethral valves. MATERIALS AND METHODS: During 1953 to 2003 a total of 200 male patients were treated for posterior urethral valves at our institution and of these 193 could be followed for renal outcome. Followup data on patients treated with dialysis or kidney transplantation were collected from patient records and the Finnish Kidney Transplantation Registry, and data on deceased patients were collected from hospital records and the Finnish Population Register Centre. RESULTS: Median patient age at evaluation was 31 years (range 6 to 69). Of the 193 patients followed 44 (22.8%) had progression to end stage renal disease. According to a Kaplan-Meier analysis the lifetime risk of end stage renal disease was 28.5% (SE 3.8%). No patient had end stage renal disease after the age of 34 years. The lowest serum creatinine value during postoperative year 1 was associated with speed of progression to end stage renal disease. Early presentation, pneumothorax, bilateral vesicoureteral reflux and recurrent urinary tract infections after the abolition of urethral obstruction were associated with an increased risk of end stage renal disease at followup. CONCLUSIONS: Congenital obstructive uropathy can lead to end stage renal disease during childhood or young adulthood. However, the risk of end stage renal disease seems to decrease eventually. Poor kidney function at presentation is associated with worse renal prognosis.

Lower urinary tract symptoms in adults treated for posterior urethral valves in childhood: matched cohort study.

PURPOSE: We compared the prevalence and bother of lower urinary tract symptoms in adults treated for posterior urethral valves in childhood and population based controls. MATERIALS AND METHODS: Questionnaires were mailed to patients 18 years and older treated at our institution for posterior urethral valves. Of the 124 patients 68 (64.2%) participated, 18 were unavailable and 38 did not participate. Age and sex matched controls were randomly identified from a population based study (response proportion 62.4%). Danish Prostatic Symptom Score was used to assess occurrence (never/rarely/often/always) and bother (none/small/moderate/major) of 12 different lower urinary tract symptoms. Chi-square test was used for the analyses stratified by patient/control status, with the 4-point ordinal scale as the outcome. RESULTS: Median age of 68 patients with posterior urethral valves and 272 controls (ratio 1:4) was 38.5 years (range 18 to 57). Overall, at least 1 moderate or severe lower urinary tract symptom was reported by 32.4% of patients with posterior urethral valves and 15.8% of controls (p=0.002). Mild hesitancy, weak stream, incomplete emptying and straining were reported twice as often by patients with posterior urethral valves as by controls (p<0.05). Prevalence of any urgency incontinence (14.7% vs 4.8%, p=0.014) and any stress incontinence (11.8% vs 3.0%, p=0.005) was increased at least 3-fold in patients with posterior urethral valves compared to controls. Furthermore, prevalence of bother from several lower urinary tract symptoms was increased approximately 2-fold in patients with posterior urethral valves compared to controls (p<0.05). However, most patients and controls reported no or small bother. CONCLUSIONS: In adulthood the occurrence and bother of most lower urinary tract symptoms are increased approximately 2-fold in patients with posterior urethral valves compared to the general population. However, in this cohort of young and middle-aged men most symptoms are mild.

Vesicoureteral reflux in conjunction with posterior urethral valves.

PURPOSE: We evaluated the link between primary kidney function and vesicoureteral reflux in patients with posterior urethral valves. We also analyzed the timing of the resolution of reflux after release of urethral obstruction. MATERIALS AND METHODS: We retrospectively analyzed records and x-ray results for 200 patients with posterior urethral valves treated at our institution between 1953 and 2003. Of these patients 197 were evaluated for vesicoureteral reflux. RESULTS: Bilateral vesicoureteral reflux was present in 73 patients (37%) and unilateral reflux in 54 (27%). Of 99 cases of posterior urethral valves diagnosed postnatally the diagnosis was made at a younger age when reflux was present (p <0.001). Patients with reflux (especially bilateral) had significantly higher serum creatinine levels at presentation and 6 and 12 months postoperatively compared to patients without reflux. In unilateral cases the split functions of refluxing kidneys were significantly decreased. Reflux resolved spontaneously at a median of 1.28 years (range 0.04 to 15.16) after treatment of posterior urethral valves, resolving more rapidly in patients with unilateral disease. Among 200 poorly functioning kidneys 35 with reflux (18%) were removed. CONCLUSIONS: In patients with posterior urethral valves vesicoureteral reflux is often associated with poorly functioning kidneys. Accordingly patients with bilateral reflux have decreased overall kidney function. Reflux resolves in half of ureters within 2 years after valve ablation. Reflux resolves more rapidly in unilateral cases.

Posterior urethral valves: primary voiding pressures and kidney function in infants.

PURPOSE: We evaluated whether high voiding pressures in patients with posterior urethral valves are associated with reduced kidney function. MATERIALS AND METHODS: A total of 25 children younger than 12 months with posterior urethral valves underwent urodynamic evaluation within 15 days of valve ablation between 1994 and 2007. Six patients underwent primary urodynamics before and 19 after valve ablation. A total of 17 patients underwent repeat studies after 1 month and 1 year. Maximum detrusor pressures during voiding and cystometric bladder capacity were compared with kidney function tests. Maximum detrusor pressures during voiding was compared with a control group and data from other studies of male infants. RESULTS: At presentation median cystometric bladder capacity was 22 ml (range 5 to 125) and maximum voiding pressure was 112 cm H(2)O (40 to 331). There was no statistical difference in bladder capacity and voiding pressures before and after valve ablation. Also, patients with and without vesicoureteral reflux had similar bladder capacities and voiding pressures. There was no association between primary voiding pressures and serum creatinine levels or kidney split function during the first year of life. Primary voiding pressures were about the same as in a control group and in previous studies of males who were healthy, who had reflux or whose status was post-pyelonephritis. Voiding pressures had decreased and bladder capacity had increased significantly at 1-year followup. CONCLUSIONS: Voiding pressures in infants with posterior urethral valves are as high as but not higher than other male infants. High voiding pressures postnatally are not associated with reduced kidney function.

Urinomas associated with posterior urethral valves.

PURPOSE: We evaluated the incidence and clinical implications of urinomas in boys with posterior urethral valves. Our secondary aim was to evaluate the treatment modalities of urinomas. MATERIALS AND METHODS: We retrospectively reviewed the hospital data of 200 patients with posterior urethral valves treated between 1953 and 2003. Documentation was sufficient in 196 cases to evaluate the presence of urinomas. A group of 69 patients with posterior urethral valves without urinoma served as controls. RESULTS: Of 196 patients 17 (9%) had urinoma. However, the incidence of urinoma increased to 15% after ultrasonography came into standard clinical use. Nine patients had perirenal urine collection, 6 had urinary ascites and 2 had urinothorax. At presentation median serum creatinine values were similar in patients with urinoma (145 mumol/l, range 54 to 431) and controls (126 mumol/l, 19 to 593, p = 0.547). Creatinine decreased similarly in patients with and without urinoma after the obstruction was relieved. Vesicoureteral reflux was detected in 69% of the patients with urinoma and in 76% of the controls. Median split function on the side of the urinoma was 51% (range 38% to 70%) on (99m)technetium diethylenetetramine pentaacetic acid scintigraphy. During childhood end-stage renal failure developed in 4 of the 16 patients (25%) with urinoma and in 16 of the 69 controls (23%). CONCLUSIONS: The true incidence of urinomas is probably close to 15% in patients with posterior urethral valves. Renal function is similar in patients with posterior urethral valves with and without urinoma. In asymptomatic cases urinomas apparently do not require any specific treatment.

Posterior urethral valves are often associated with cryptorchidism and inguinal hernias.

PURPOSE: We evaluated the incidence of cryptorchidism and inguinal hernias in patients with posterior urethral valves, and compared characteristics in patients with and without cryptorchidism or inguinal hernia. MATERIALS AND METHODS: A total of 200 patients with posterior urethral valves treated between 1953 and 2003 were identified from a hospital database. Patient records were retrospectively reviewed. The state of testicular descent and the presence of inguinal hernias were recorded in 192 patients. Patient characteristics were analyzed. RESULTS: Of 192 patients 31 (16%) had cryptorchidism, which was bilateral in 9 (29%). A total of 21 patients (11%) had inguinal hernias that were not associated with cryptorchid testes. The patients with cryptorchidism, and to some extent the patients with hernias, appeared to have a more severe form of posterior urethral valves than those without cryptorchidism. At the time of diagnosis the median serum creatinine concentration was 100 mumol/l (range 38 to 460) in boys with cryptorchidism and 87 (14 to 593) in boys without cryptorchidism (p = 0.131). At 6-month followup the median serum creatinine levels were 90 mumol/l (range 31 to 573) in patients with cryptorchidism and 45 (19 to 504) in patients without cryptorchidism (p = 0.006). Cryptorchidism was also more common in cases diagnosed neonatally compared to those diagnosed at a later age (14 of 52 patients, 27% vs 14 of 112, 12.5%, respectively, p = 0.027). CONCLUSIONS: The incidence of cryptorchidism and inguinal hernias requiring surgery is high in patients with posterior urethral valves. Patients with cryptorchidism appear to have a more severe form of posterior urethral valves than those with normal testes.