Further predictors of renal dysplasia in fetal obstructive uropathy: bladder pressure and biochemistry of 'fresh' urine

Urine was aspirated on two consecutive days from the dilated bladder of nine fetuses with lower urinary tract obstruction. Gestational age ranged from 17 to 35 weeks. Renal dysplasia was diagnosed histologically in four fetuses, whereas the other five had normal renal histology or only partial dysplasia. Urinary sodium (Na+) and osmolality (Osm) decreased significantly in the second urine sample 1 day after bladder emptying (median decrease: Na+ = -11.3 per cent; Osm = -13.3 per cent). Although there were no significant differences between fetuses with or without renal dysplasia, normalization of an initially raised urine Na+ concentration occurred at the second sample in a fetus with partially normal renal histology, thus correcting a false-positive diagnosis of dysplasia. Bladder pressure was measured at the time of the first urine sampling in seven fetuses and in a further eight with bladder outlet obstruction undergoing a single urine aspiration at 18-28 weeks. Bladder pressure was increased above the reference range in 8 of 15 fetuses with urinary obstruction, but there was no correlation between pressure and the degree of impairment of renal function. Although no conclusive clinical guidelines can be drawn from this study for the evaluation of fetal renal function, these findings suggest that, in lower urinary tract obstruction, tubular reabsorption is impeded by the standing pressure in the urinary tract and that improvement of renal function may occur following relief of obstruction.     

Fetal urine biochemistry in the assessment of obstructive uropathy.

In 60 fetuses with obstructive uropathy, sodium, total calcium, urea, and creatinine were measured in samples obtained by "urodochocentesis" or pyelocentesis at 16 to 36 weeks' gestation. The patients were retrospectively assigned into two groups on the basis of outcome. Group 1 (n = 20) included infants who either had normal postnatal renal function or absence of prenatal renal dysplasia. Group 2 included infants who either had histologic evidence of renal dysplasia or subsequently developed renal failure. In group 1 the urinary sodium decreased and creatinine increased with gestation, demonstrating maturation in fetal renal function. In group 2 the urinary sodium and calcium were higher and the urinary urea and creatinine were lower than in group 1. The best predictor of outcome was the combination of either high calcium or high sodium with a positive predictive value of 91.3% and negative predictive value of 77.7%. In the antenatal evaluation of obstructive uropathy, fetal urinary biochemistry provides useful information for more accurate counseling of the parents and a rational basis for selecting patients who may benefit from intrauterine therapeutic interventions.     

Diagnosis and outcome of fetal lower urinary tract obstruction in the northern region of England

OBJECTIVE: We reviewed the prenatal and postnatal management of fetal lower urinary tract obstruction (LUTO) in a large geographically defined population. METHODS: The records of 113 cases of LUTO seen over a 14-year period were examined. The predictive accuracy of prenatal findings for chronic renal failure (CRF) and a comparison of prenatal-suspected and non-suspected cases were made. RESULTS: The incidence of LUTO was 2.2 in 10 000 births. During the study period, prenatal detection improved from 33 to 62%. Sensitivity of prenatal ultrasound detection of renal dysplasia and fetal urinary sodium, calcium, and beta2-microglobulin for CRF or renal dysplasia on autopsy were 59, 33, 66, and 63% respectively. Compared to undetected cases, those detected prenatally had higher mortality and a higher rate of CRF at 24 months (17% vs 57%, p < 0.01). CONCLUSION: Our observations confirm the poor prognosis associated with fetal LUTO. The value of serial fetal urine biochemistry, other prenatal predictors of postnatal renal function, and the benefits of vesicoamniotic shunting require larger series and longer follow-up.     

The nonpredictive value of fetal urinary electrolytes: preliminary report of outcomes and correlations with pathologic diagnosis

Fetal urine was sampled 12 times in nine fetuses with sonographically diagnosed urinary tract obstruction to assess renal function. By previously proposed criteria, four fetuses were predicted to have poor renal function. Two of these fetuses were found to have renal dysplasia on autopsy after elective termination. The other two died in the neonatal period but only one of these had histologic evidence of renal dysplasia. Five fetuses were predicted to have good renal function. Three of these developed renal failure after birth, one was found to have renal dysplasia on autopsy after elective termination, and one is alive and well. We conclude that fetal urine electrolytes are not necessarily an accurate predictor of neonatal renal function.     

Ultrasound screening for fetal urinary tract malformations: a prospective study in general population

Routine ultrasound examination at a first level ultrasound unit was performed on 4586 fetuses in general pregnant population at 18 and 34 weeks, to detect urinary tract malformations. Suspected renal abnormality was confirmed by postnatal investigations. Infants were followed up to 2-4 years to detect any renal malformations missed in screening. Urinary tract abnormalities were observed antenatally in 27 fetuses, eight cases at 18 weeks, and 19 cases at 34 weeks. An anteroposterior diameter of renal pelvis of 1 cm or more was the criterion for fetal hydronephrosis, which was the main ultrasound finding in 18 fetuses showing 24 hydronephrotic kidneys. In five cases, slight hydronephrosis disappeared spontaneously after birth, explaining the five 'false positive' cases of the study. Four children had renal abnormalities that were missed antenatally. The incidence of true urinary tract malformations detected by screening antenatally was 0.48%, and the overall incidence after 2-4 years follow-up was 0.57%, which is much higher than reported earlier in series without routine ultrasound screening. The antenatal screening showed a sensitivity of 84.6%, a specificity of 99.9%, a positive predictive value of 81.5%, and a negative predictive value of 99.9%. The main differential diagnostic problems occurred in two fields: in differentiating (1) functional hydronephrosis from obstructive uropathy, and (2) multicystic renal dysplasia of Potter's type IV from severe hydronephrosis. The prenatal diagnosis in cases with definitive renal abnormality corresponded to the postnatal diagnosis in 19/22 (86.4%) of the cases. 68% of the infants with urinary tract anomaly survived, 60% of them undergoing postnatal surgery.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sequential invasive assessment of fetal renal function and the intrauterine treatment of fetal obstructive uropathies

Persistent fetal lower urinary tract obstruction carries a very poor prognosis secondary to damaged renal capacity and oligohydramnios, with its related pulmonary hypoplasia. Several attempts in the past several years to divert urinary flow via an intrauterine shunt have generally been disappointing, primarily because of poor patient selection. In this study we report our experiences with aggressive decompression of megacystis in 11 patients, the value in selected cases of sequential evaluations of fetal urine biochemistry, and the success of intrauterine bladder shunting procedures in appropriately chosen patients. Our data suggest that a single fetal urine determination may be insufficient to declare irreversible damage. Following decompression, improvement in urine biochemistry or its lack may be more likely representative of ultimate outcome. Decompression by either needle aspiration or intrauterine shunting is warranted in carefully selected cases and can save fetuses that are otherwise very likely doomed.     

Failure to detect fetal obstructive uropathy by second trimester ultrasound

The prenatal diagnosis, management and outcome of an hereditary obstructive uropathy is presented. Serial ultrasonic assessment of the fetal urinary tract was carried out from the early second trimester onward. Slight bilateral hydronephrosis as a first sign of obstructive uropathy was only established as late as 30 weeks of gestation. On the basis of weekly ultrasound scans, a conservative approach was adopted. In view of fetal maturity, labour was induced at 36 weeks resulting in the vaginal delivery of a male infant with moderate bilateral hydronephrosis. Neonatally, anuria developed due to bilateral obstruction of the ureters as a result of increasing bladder wall hypertrophy due to urethral valves. A bilateral uretero-cutaneostomy was carried out. The infant so far develops normally, and renal function is normal for age. Women at risk for fetal obstructive uropathy should have ultrasonic monitoring throughout pregnancy.     

The effects of overcoming experimental bladder outflow obstruction in fetal sheep

Objective: To develop an ovine model of fetal bladder outflow obstruction and to investigate the effect on the kidney of surgical relief of the obstruction in the prenatal period. Methods: Ultrasound examination and amniocentesis were performed on 68 date-bred pregnant ewes at day 57 of pregnancy (term = 150 days). Fetal gender was determined using a molecular technique to identify single male fetuses. The urethra and urachus were ligated at hysterotomy on 20 of these fetuses at 75 days' gestation. Comparisons were made with six controls that did not undergo operation. Changes that occurred in fetal urinary tract appearance were detected using serial ultrasound examinations. Seven obstructed cases chosen at random had further prenatal surgery on day 94 to decompress the obstructed urinary tract by vesicostomy. The animals were killed at 110 days' gestation and post-mortem studies were performed. Results: Fourteen days after surgical obstruction, there were increases in the summed renal lengths (33 mm vs. 28 mm, p = 0.003) and renal pelvis anteroposterior (A-P) diameters (8 mm vs. 5.5 mm, p = 0.02). In the group allocated to receive surgical decompression, 9 days' relief of obstruction resulted in significant reductions in summed renal lengths (30 mm vs. 41 mm, p = 0.024; controls 31 mm) and renal pelvis A-P diameters (5.8 mm vs. 8.9 mm, p = 0.012; controls < 2 mm). Post-mortem histological examination in the surgical decompression group revealed an estimated number of glomeruli similar to controls and greater than in the obstructed cases. Conclusion: Surgical relief of fetal bladder outflow obstruction in ovine mid-pregnancy results in improved renal appearance on ultrasonic and histopathological examinations.     

Systematic review of accuracy of fetal urine analysis to predict poor postnatal renal function in cases of congenital urinary tract obstruction

OBJECTIVE: To evaluate the clinical usefulness of analysis of fetal urine in the prediction of poor postnatal renal function in cases of congenital urinary tract obstruction. METHODS: A systematic review was performed. We conducted extensive electronic searches (database inception-2006). The reference lists of articles obtained were searched for any further articles. Two reviewers independently selected the articles in which the accuracy of fetal urinalysis was evaluated to predict poor postnatal renal function. There were no language restrictions. Data were extracted on study characteristics, quality and results, to construct 2 x 2 tables. Likelihood ratios for positive (LR+) and negative (LR-) test results were generated for the different fetal urinary analytes at various thresholds. RESULTS: There were 23 articles that met the selection criteria, including a total of 572 women and 63 2 x 2 tables. The two most accurate tests were calcium > 95th centile for gestation (LR + 6.65, 0.23-190.96; LR - 0.19, 0.05-0.74) and sodium > 95th centile for gestation (LR + 4.46, 1.71-11.6; LR - 0.39, 0.17-0.88). beta(2)-microglobulin was found to be less accurate (LR + 2.92, 1.28-6.69; LR - 0.53, 0.24-1.17). CONCLUSION: The current evidence demonstrates that none of the analytes of fetal urine investigated so far can be shown to yield clinically significant accuracy to predict poor postnatal renal function.     

Fetal obstructive uropathy: is urine sampling useful for prenatal counselling?

OBJECTIVES: To evaluate whether fetal urinary sodium and chloride provide clinically useful information in addition to ultrasound in bilateral obstructive uropathy. METHODS: Sonographic features and urinary concentrations of sodium and chloride were evaluated in fetuses with bilateral obstructive uropathy. After a minimum of 12 months of postnatal follow-up, cases that developed increased serum creatinine (greater than 50 micromol/L) were compared with those that did not. RESULTS: Of the cases studied, 16/35 died perinatally, all showing anamnios and markedly elevated urinary electrolytes. Of the survivors, ten maintained normal postnatal serum creatinine, whereas nine did not. The frequency of reduced amniotic fluid/olygohydramnios was higher in cases that developed increased serum creatinine (four out of nine) than in those that did not (nil). Sodium above the 95th percentile was 100% specific and 44% sensitive to predict an increased serum creatinine during early infancy, while chloride above the 95th percentile was 70% specific and 56% sensitive. All seven cases in which urinary sodium was elevated and/or amniotic fluid volume was reduced developed renal failure. CONCLUSION: Urine sampling slightly improved renal function prediction, but this must be balanced against its fetal risks.     

The early development of the fetal kidney-an in utero sonographic evaluation between 13 and 22 weeks' gestation

OBJECTIVES: To establish a nomogram for early fetal kidney development during early gestation. METHODS: The study is a prospective, cross-sectional evaluation of 275 male and female fetuses between 13 and 22 weeks in normal singleton pregnancies. Measurements of fetal kidney length were performed by high resolution transvaginal ultrasonography between 14 and 17 weeks' gestation, and by transabdominal ultrasonography beyond 18 weeks' gestation. RESULTS: Adequate kidney length measurements were obtained in all 275 normal fetuses as well as in six fetuses with urinary tract anomalies. Kidney length as a function of gestational age was expressed by the regression equation: (square root) kidney length (mm) = -11.66 + 1.52 x gestational age (weeks). The correlation coefficient, r = 0.983 was found to be highly statistically significant (p < 0.0001). The normal mean and the 90% prediction limits were defined. Four cases with single kidney and two cases with posterior urethral valve had kidney length above the 95% upper limit. CONCLUSION: The present data offer a normal range of fetal kidney length from early stages of gestation that may allow intrauterine assessment of its development. It may also be helpful in the early prenatal diagnosis of renal abnormalities.     

In utero therapy for lower urinary tract obstruction.

Lower urinary tract obstruction has a significant impact on neonatal and child health. Pulmonary hyperplasia and renal impairment could be direct or indirect consequences of this condition leading to significant morbidity and mortality. Evaluation of fetuses with suspected lower urinary tract obstruction is performed not only to confirm the diagnosis but also to assess renal prognosis. Ultrasound examination and urinary analysis aid in the evaluation of these fetuses. The decision to perform fetal intervention in these cases is a difficult one. Vesico-amniotic fetal shunting, open fetal surgery and more recently endoscopic fetal surgery for this condition are available as possible modalities of fetal intervention. Case selection for fetal intervention is extremely important in order to both avoid unnecessary intervention in those unlikely to survive, and also to avoid procedure related complications in fetuses likely to do well without intervention. Vesico-amniotic shunting has the advantage of bypassing the obstruction, however it is often associated with complications. Open fetal surgery is not usually recommended because of the complications and high fetal loss rate. Endoscopic surgery to visualise and treat the cause of lower urinary tract obstruction has been tried. Fetal endoscopic surgery is in its infancy and endoscopic procedures are limited to a few groups. This current review addresses evaluation, case selection and therapeutic options for lower urinary tract obstruction in utero. It also discusses the limited data against which the efficacy of the various options can be assessed. The current state of fetal intervention is detailed in the present review.     

Fetal renal defects: associated malformations and chromosomal defects.

During a 6-year period (1985-1990) blood karyotyping was performed in 682 fetuses with renal defects. There were: 276 fetuses with mild hydronephrosis; 206 with moderate/severe hydronephrosis; 173 with multicystic dysplasia, and 27 with renal agenesis. The overall incidence of chromosomal abnormalities was 12% (trisomies, n = 63; deletions, n = 9; triploidies, n = 5, and sex chromosome aneuploidies, n = 8). There were more than twice as many males than females, but the incidence of chromosomal defects in females was almost double (18%) than in males (10%). Furthermore, compared to the overall maternal age-related risk, the risk for fetal chromosomal abnormalities was three times higher when there was an isolated renal defect and thirty times higher when there were additional malformations. The risk of chromosomal abnormalities was similar for fetuses with unilateral or bilateral involvement, different types of renal defects, urethral or ureteric obstruction, and oligohydramnios or normal/reduced amniotic fluid volume. Nevertheless, the patterns of chromosomal abnormalities, and consequently that of associated malformations, were related to the different types of renal defects.     

Perinatal outcome in fetuses with megacystis in the first half of pregnancy

OBJECTIVE: To present the outcome of a consecutive series of 19 fetuses referred to our center for megacystis in the first half of the pregnancy. STUDY DESIGN: Retrospective analysis. METHODS: 19 cases of early fetal megacystis were reviewed. Inclusion criteria were the visualization of an enlarged bladder with a maximum longitudinal diameter >10 mm and a gestational age of no more than 19 weeks. RESULTS: The median gestational age at diagnosis was 16 weeks (range 12-19 weeks). The median maximum longitudinal diameter of the fetal bladder at the time of diagnosis was 21 mm (range 11-35 mm). The fetal megacystis was associated with another extra renal anomaly in six cases (30%). There was no fetus with abnormal karyotype. Termination of pregnancy was performed in 11 cases because of the severity of the renal disease. One spontaneous intrauterine death occurred. A vesicoamniotic shunt was inserted in three cases, two of which died in utero. The surviving fetus that was shunted died in the neonatal period from acute renal failure. In the remaining four fetuses, resolution of the megacystis occurred spontaneously (n = 2) or following serial single-needle aspiration (n = 2). One of these had renal insufficiency requiring kidney transplantation. CONCLUSION: The outcome of fetuses with early obstructive uropathy is poor, with or without in utero therapy. Pathophysiology, clinical presentation and outcome of fetuses with early uropathy may differ from those previously described in the latter part of pregnancy.     

Hyperhomocysteinemia in pregnant rats: effects on arterial pressure, kidneys and fetal growth

OBJECTIVE: This study aimed to test the hypothesis that hyperhomocysteinemia plays a role in the development of pathological changes similar to human preeclampsia in pregnant rats. STUDY DESIGN: Arterial pressure and 24-h urinary excretion of proteins and electrolytes were measured during pre-pregnancy, pregnancy and postpartum periods in control (n = 12) and methionine-treated (2.0 g/kg/day, n = 11) Sprague-Dawley rats. Rats were then sacrificed at the end of this protocol and renal histological examination was performed. In another protocol, control (n = 6) and methionine-treated (n = 6) rats were anaesthetized at day 20 of gestation and pregnancy outcome was assessed. Hemodynamic and renal excretory differences between groups were analyzed using ANOVA and differences in renal histology and gestation outcome using t-test. RESULTS: Serum homocysteine in the methionine group (24.0+/-2.0 micromol/L) was significantly higher compared with controls (8.5+/-0.5 micromol/L). Systolic pressure, urinary protein excretion and renal histological changes were not significantly different between the two groups. However, fetal weights were significantly smaller and percent of dead fetuses were 15% higher in methionine-treated compared with control rats. CONCLUSION: Hyperhomocysteinemia is unlikely to cause maternal hypertension, proteinuria or renal damage in pregnant rats. However, hyperhomocysteinemia may restrict fetal growth and increase fetal mortality.     

Perinatal obstructive nephropathy

Significant advances have been made recently in elucidating the cellular consequences of urinary tract obstruction during renal development. Urinary tract obstruction impairs growth and maturation of the kidney, and can also cause renal maldevelopment. This includes a reduction in the number of nephrons, tubular atrophy, and progressive interstitial fibrosis. Apoptosis (programmed cell death) accounts for much of the loss of tubular epithelial cells. Factors contributing to apoptosis include stretching of cells in dilated tubules, altered renal production of growth factors, and infiltration of the renal interstitium by macrophages. Two major controversies remain regarding the surgical management of congenital obstructive nephropathy: first, which fetuses with bladder outlet obstruction should undergo prenatal intervention, and second, which infants should undergo early pyeloplasty for ureteropelvic junction obstruction? Even after successful surgery for congential obstructive nephropathy, all patients should be followed for hypertension, proteinuria, or renal deterioration.     

Vesicoamniotic shunting using a double-basket catheter appears effective in treating fetal bladder outlet obstruction

BACKGROUND: To estimate the effect of vesicoamniotic shunting using a double-basket catheter on treating fetal bladder outlet obstruction. METHODS: A retrospective study involving 8 prenatally diagnosed bladder outlet obstruction cases that underwent vesicoamniotic shunt placement using a double-basket catheter from 1998 to 2004. Patients were followed-up for prenatal and neonatal outcome analyses. RESULTS: Vesicoamniotic shunting was performed in 8 fetuses aged between 13.7 and 25.4 weeks' gestation (mean+/-SD, 19.7+/-3.5 weeks). Final diagnoses included 5 posterior urethral valves, 1 cloacal anomaly, 1 urethral stenosis, and 1 unknown. There were no maternal complications associated with the procedures. One woman diagnosed as having a fetus with posterior urethral valves decided to terminate her pregnancy and one fetus died in uterus spontaneously. Six women delivered live babies, and one baby required postnatal ventilatory support. Postnatal follow-up ranged from 3 to 60 months. Of the 6 newborns, 4 survived with normal renal function, 1 had renal insufficiency, and 1 died of renal failure at 3 months of age. CONCLUSIONS: Vesicoamniotic shunt placement using a double-basket catheter may be effective in improving perinatal and neonatal outcomes through long-term decompression of the fetal urinary tract in carefully selected cases.     

尿钙及尿微量白蛋白检测在妊高征早期诊断中的临床意义

目的　评价尿钙及尿微量白蛋白检测在妊高征早期诊断中的临床意义。方法　收集９８ 例孕２４～３２ 周健康孕妇的２４ 小时尿样,采用自动生化仪测定尿钙排泄量,放射免疫法测定尿微量白蛋白的排泄量,按最终是否发生妊高征分成妊高征组（１４ 例） 和正常妊娠组（８４ 例） 。结果　妊高征组尿钙排泄量为（１－４３±０－３７） ｍｍｏｌ／２４ｈ ,正常妊娠组为（３－２６±０－７５） ｍｍｏｌ／２４ｈ,妊高征组尿钙排泄量显著低于正常妊娠组（ Ｐ＜ ０－００５） 。妊高征组尿微量白蛋白排泄量为（１２－６８ ±６－８１） μｇ／２４ｈ ,正常妊娠组为（６－０８±３－４８） μｇ／２４ｈ,妊高征组尿微量白蛋白排泄量显著高于正常妊娠组（ Ｐ＜ ０－０５）。结论　在妊高征临床症状出现４～８ 周之前,即出现尿钙排泄量减少及尿微量白蛋白排泄量增多。这一特征可作为妊高征早期诊断的指标。     

Urinary excretion rates of calcium and magnesium in normal and complicated pregnancies

In this cross-sectional study calcium and magnesium metabolism was investigated in normal pregnancies (n = 34) and pregnancies complicated by either fetal growth retardation of hypertension with or without fetal growth retardation (SGA newborns) (n = 30). Special attention has been given to the renal excretion rates of calcium and magnesium and their relationship to creatinine and sodium clearances. No differences were noted in the third trimester of pregnancy between the normal and complicated pregnancies in calcium or magnesium metabolism except for an increased serum magnesium in the SGA group. Comparing the post-partum period to normal pregnancy the following results were observed: (i) serum ionic calcium levels showed no differences; (ii) urinary calcium excretion was increased as a result of increased calcium clearance. A striking feature was the fact that the fractional calcium clearance was not increased, in contrast to the increase in relative calcium clearance. The observed results can be explained by an increased GFR and a possible dissociation between the sodium and calcium handling in the cortical thick ascending Limb of Henle's Loop.     

Diagnostik der pränatalen Nierenfunktion

The evaluation of prenatal kidney function by fetal urinalysis for electrolytes, osmolality, proteins, amino acids, urea, creatinine and glucose is reviewed. Interpretation of the data requires knowledge of the normal urine values in healthy fetuses and due consideration for gestational age and maternal and fetal factors. Up to now there is no general consensus in the literature on the normal fetal urine composition. In cases with ultrasonographically detectable oligohydramnios and urinary tract obstruction fetal urinalysis has been proposed as a means of predicting postnatal kidney function. However, the present methods lack sensitivity and specificity, which makes an accurate prognosis in the individual case very difficult.