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      Variación de la microglobulina beta-2 en orina fetal en punciones sucesivas previo a derivación vesicoamniótica antenatal Translated title: Prognostic value of fetal urine beta2 microglobuline in vesicoamniotic shunting therapy for fetal obstructive uropathy

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          Abstract

          Antecedentes y objetivos. La uropatía obstructiva fetal puede ser tratada precozmente mediante la colocación de derivación vesicoamniótica intrauterina. Los criterios de tratamiento incluyen la ausencia de malformaciones mayores asociadas, cariotipo normal y función renal conservada demostrada por microglobulina beta-2 < 4 mg/dL. Por la capacidad de concentración de orina en la vejiga fetal, si en una primera punción el valor de microglobulina beta-2 es superior al punto de corte, se requiere una segunda punción a las 48 a 72 horas para verificar el valor en orina nueva, no concentrada, que correspondería al valor real. Objetivo. Determinar el comportamiento de la variación de los niveles de microglobulina beta-2 en 2 muestras seriadas de orina fetal, con intervalo de 48 a 72 horas. Pacientes. Fetos con diagnóstico de uropatía obstructiva referidos al Centro Médico Docente La Trinidad, para establecer la posibilidad de omisión de la segunda punción en caso de encontrarse un patrón específico de comportamiento de la disminución de los valores. Métodos. Se realizó un estudio clínico unicéntrico, descriptivo y longitudinal, incluyendo a 15 embarazadas cuyos fetos fueron diagnosticados con uropatía obstructiva y sin cromosopatías, practicándoseles vesicocentesis seriada (48 a 72 horas) para biometría urinaria. Resultados. Los valores de microglobulina beta-2 resultaron > 4 mg/dL en los 15 casos con la primera vesicocentesis, y disminuyeron a < 4 mg/dL en 7 casos (46,6%) en la segunda vesicocentesis. En todos los casos cuando la microglobulina beta-2 fue < 8 mg/dL en la primera vesicopunción, siempre disminuyó a valores muy próximos a 4 mg/dL (máximo de 4,3 mg/dL) en la segunda vesicopunción. Conclusiones. Se plantea la colocación in útero de derivaciones vesicoamnióticas en los casos de uropatía obstructiva fetal cuando la microglobulina beta-2 sea < 8 mg/dL en la primera vesicopunción, omitiendo realizar una segunda vesicopunción.

          Translated abstract

          Introduction. Fetal obstructive uropathy can be treated early in pregnancy by intrauterine vesicoamniotic shunting, immediately after diagnosis by ultrasound, in specific cases with a favorable prognosis in renal function using fetal urine beta2 microglobulin. Objective: To determine the changes of beta-2 microglobulin in consecutive samples of fetal urine in 48 - 72 hour-intervals in fetuses with obstructive uropathy at 16 weeks of gestation. Methods: We designed a descriptive and longitudinal study, including 15 pregnant women whose fetuses were diagnosed with obstructive uropathy without chromosomal abnormalities, performing vesicocentesis for urinary biometry. Results: Beta-2 microglobulin values were higher than 4 mg/dL in the first vesicocentesis of all 15 cases and decreased to less than 4 mg/dL in 7 cases (46.6%) after the second vesicocentesis. In all cases when beta-2 microglobulin was less than 8 mg/dL in the first vesicocentesis, there was a decrease to nearly 4 mg/dL (maximum 4.3 mg/dL) in the second vesicocentesis. Conclusions: Vesicoamniotic shunting should be performed in all cases of fetal obstructive uropathy when the values of beta-2 microglobulin are less than 8 mg/dL in the first vesicocentesis.

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          Percutaneous vesicoamniotic shunting versus conservative management for fetal lower urinary tract obstruction (PLUTO): a randomised trial

          Summary Background Fetal lower urinary tract obstruction (LUTO) is associated with high perinatal and long-term childhood mortality and morbidity. We aimed to assess the effectiveness of vesicoamniotic shunting for treatment of LUTO. Methods In a randomised trial in the UK, Ireland, and the Netherlands, women whose pregnancies with a male fetus were complicated by isolated LUTO were randomly assigned by a central telephone and web-based randomisation service to receive either the intervention (placement of vesicoamniotic shunt) or conservative management. Allocation could not be masked from clinicians or participants because of the invasive nature of the intervention. Diagnosis was by prenatal ultrasound. The primary outcome was survival of the baby to 28 days postnatally. All primary analyses were done on an intention-to-treat basis, but these results were compared with those of an as-treated analysis to investigate the effect of a fairly large proportion of crossovers. We used Bayesian methods to estimate the posterior probability distribution of the effectiveness of vesicoamniotic shunting at 28 days. The study is registered with the ISRCTN Register, number ISRCTN53328556. Findings 31 women with singleton pregnancies complicated by LUTO were included in the trial and main analysis, with 16 allocated to the vesicoamniotic shunt group and 15 to the conservative management group. The study closed early because of poor recruitment. There were 12 livebirths in each group. In the vesicoamniotic shunt group one intrauterine death occurred and three pregnancies were terminated. In the conservative management group one intrauterine death occurred and two pregnancies were terminated. Of the 16 pregnancies randomly assigned to vesicoamniotic shunting, eight neonates survived to 28 days, compared with four from the 15 pregnancies assigned to conservative management (intention-to-treat relative risk [RR] 1·88, 95% CI 0·71–4·96; p=0·27). Analysis based on treatment received showed a larger effect (3·20, 1·06–9·62; p=0·03). All 12 deaths were caused by pulmonary hypoplasia in the early neonatal period. Sensitivity analysis in which non-treatment-related terminations of pregnancy were excluded made some slight changes to point estimates only. Bayesian analysis in which the trial data were combined with elicited priors from experts suggested an 86% probability that vesicoamniotic shunting increased survival at 28 days and a 25% probability that it had a large, clinically important effect (defined as a relative increase of 55% or more in the proportion of neonates who survived). There was substantial short-term and long-term morbidity in both groups, including poor renal function—only two babies (both in the shunt group) survived to 2 years with normal renal function. Seven complications occurred in six fetuses from the shunt group, including spontaneous ruptured membranes, shunt blockage, and dislodgement. These complications resulted in four pregnancy losses. Interpretation Survival seemed to be higher in the fetuses receiving vesicoamniotic shunting, but the size and direction of the effect remained uncertain, such that benefit could not be conclusively proven. Our results suggest that the chance of newborn babies surviving with normal renal function is very low irrespective of whether or not vesicoamniotic shunting is done. Funding UK National Institute of Health Research, Wellbeing of Women, Hannah Eliza Guy Charity (Birmingham Children's Hospital Charity).
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            Fetal intervention in obstructive uropathy: prognostic indicators and efficacy of intervention.

            Management of the fetus with bilateral hydronephrosis is controversial; ability to predict outcome and efficacy of prenatal intervention are unknown. We studied 40 fetuses referred for ultrasonography, examination of fetal urine, and possible therapy. We retrospectively assigned fetuses to a good prognosis group if fetal urine was hypotonic (sodium less than 100 mEq/L, chloride less than 90 mEq/L, osmolarity less than 210 mOsm/L) and there was no ultrasonographic evidence of dysplasia; we assigned fetuses to a poor prognosis group if even one criterion was abnormal. Survival was greater in the good prognosis group than in the poor prognosis group (81% vs 12.5%; 87% vs 30%, excluding abortions) (p less than 0.005). We then attempted to assess the efficacy of prenatal urinary decompression by comparing outcome within the good and poor prognosis groups. Survival with intervention was greater in both the good prognosis group and the poor prognosis group (89% vs 70% and 30% vs 0%). In 6 of the 8 survivors in the good prognosis group, severe oligohydramnios was reversed by decompression. We conclude the fetal urine electrolyte levels and ultrasonographic appear helpful in predicting residual fetal renal function and neonatal outcome and that prenatal decompression may prevent the development of fatal pulmonary hypoplasia.
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              Congenital urinary tract obstruction: defining markers of developmental kidney injury.

              Congenital urinary tract obstruction (diagnosed antenatally by ultrasound screening) is one of the main causes of end-stage kidney disease in children. The extent of kidney injury in early gestation and the resultant abnormality in kidney development determine fetal outcome and postnatal renal function. Unfortunately, the current approach to diagnostic evaluation of the severity of injury has inherently poor diagnostic and prognostic value because it is based on the assessment of fetal tubular function from fetal urine samples rather than on estimates of the dysplastic changes in the injured developing kidney. To improve the outcome in children with congenital urinary tract obstruction, new biomarkers reflecting these structural changes are needed. Genomic and proteomic techniques that have emerged in the past decade can help identify the key genes and proteins from biological fluids, including amniotic fluid, that might reflect the extent of injury to the developing kidney.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Journal
                rgo
                Revista Peruana de Ginecología y Obstetricia
                Rev. peru. ginecol. obstet.
                Sociedad Peruana de Obstetricia y Ginecología (Lima, , Peru )
                2304-5132
                October 2018
                : 64
                : 4
                : 631-638
                Affiliations
                [01] Cincinnati OH orgnameCincinnati Children’s Hospital Medical orgdiv1Cincinnati Fetal Center orgdiv2Center for Fetal Cellular & Molecular Therapy United States
                [02] Caracas orgnameCentro Médico Docente La Trinidad Venezuela
                Article
                S2304-51322018000400014
                10.31403/rpgo.v64i2133
                bd1a0827-e559-4848-9220-57f80ec4b94f

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 09 October 2018
                : 11 October 2018
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 19, Pages: 8
                Product

                SciELO Peru

                Categories
                Simposio Cirugía Fetal en América Latina

                Uropatía obstructiva fetal,Terapia de derivación vesicoamniótica,Microglobulina beta-2,Fetal obstructive uropathy,Beta 2 macroglobulin,Vesicoamniotic shunt therapy

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