Absence of Evidence of Zika Virus Infection in Cord Blood and Urine from Newborns with Congenital Abnormalities, Indonesia.

Zika virus (ZIKV) has recently been confirmed as endemic in Indonesia, but no congenital anomalies (CA) related to ZIKV infection have been reported. We performed molecular and serological testing for ZIKV and other flaviviruses on cord serum and urine samples collected in October 2016 to April 2017 during a prospective, cross-sectional study of neonates in Jakarta, Indonesia. Of a total of 429 neonates, 53 had CA, including 14 with microcephaly. These 53, and 113 neonate controls without evidence of CA, were tested by ZIKV-specific real-time reverse transcription polymerase chain reaction (RT-PCR), pan-flavivirus RT-PCR, anti-ZIKV and anti-DENV IgM ELISA, and plaque reduction neutralization test. There was no evidence of ZIKV infection among neonates in either the CA or non-CA cohorts, except in three cases with low titers of anti-ZIKV neutralizing antibodies. Further routine evaluation throughout Indonesia of pregnant women and their newborns for exposure to ZIKV should be a high priority for determining risk.

Antenatal hydronephrosis and fetal urine sampling.

The aim of this study is to evaluate the significance of renal pelvis aspiration (RPA) in the management of antenatal hydronephrosis (AHN). This study enrolled 15 AHN cases (one twin pregnancy) that necessitated RPA for AHN. Chromosomal abnormalities, gene disorders, and additional life-threatening congenital abnormalities were eliminated prior to intrauterine interventions. Urine analysis were performed for the evaluation of renal function. Normal renal function was observed in six neonates/infants (40%) (group 1), whereas impaired renal function and various type of urinary system anomalies were observed in 9 neonates/infants (60%) (group 2) during the short-term and longitudinal follow-up periods. There were statistically significant differences in the oligohydroamniosis rate, mean fetal urine sodium value, mean fetal urine ß2-microglobulin, mean gestational week at birth, and mean birthweight values between the groups (P = 0.007, P < 0.001, P = 0.035, P < 0.001, and P = 0.001, respectively). Renal pelvis aspiration and urine analysis were substantial for the management of AHN in necessary cases. ß2-microglobulin and sodium are clinically useful markers to detect the presence of severe renal damage due to obstructive uropathy and thus, important adjuvants in the proper selection of fetuses for further antenatal interventions.

Prospective Study on Several Urinary Biomarkers as Indicators of Renal Damage in Children with CAKUT.

PURPOSE: The aim of the study was to investigate urinary levels of monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF), ß-2-microglobulin (ß2M), and FAS-ligand (FAS-L) in children with congenital anomalies of kidney and urinary tract (CAKUT) disease at risk of developing glomerular hyperfiltration syndrome. For this reason, we selected patients with multicystic kidney, renal agenesia and renal hypodysplasia, or underwent single nephrectomy. MATERIALS AND METHODS: This prospective, multicentric study was conducted in collaboration between the Pediatric Surgery Unit in Foggia and the Pediatric Nephrology Unit in Bari, Italy. We enrolled 80 children with CAKUT (40 hypodysplasia, 22 agenetic; 10 multicystic; 8 nephrectomy) who underwent extensive urological and nephrological workup. Exclusion criteria were recent urinary tract infections or pyelonephritis, age > 14 years, presence of systemic disease, or hypertension. A single urine sample was collected in a noninvasive way and processed for measuring by enzyme-linked immunosorbent assay urine levels of MCP-1, EGF, ß2M, and FAS-L. As control, urine samples were taken from 30 healthy children.Furthermore, we evaluated the urinary ratios uEGF/uMCP-1 (indicator of regenerative vs inflammatory response) and uEGF/uß2M (indicator of regenerative response vs. tubular damage). RESULTS: These results suggest that urinary levels of MCP-1 are overexpressed in CAKUT patients. Furthermore, our findings clearly demonstrated that both uEGF/uMCP-1 and uEGF/uß2M ratios were significantly downregulated in all patient groups when compared with the control group. CONCLUSION: These findings further support that CAKUT patients may, eventually, experience progressive renal damage and poor regenerative response. The increased urinary levels of MCP-1 in all groups of CAKUT patients suggested that the main factor responsible for the above effects is chronic renal inflammation mediated by local monocytes.

Screening for seemingly healthy newborns with congenital cytomegalovirus infection by quantitative real-time polymerase chain reaction using newborn urine: an observational study.

OBJECTIVE: Approximately 8-10% of newborns with asymptomatic congenital cytomegalovirus (cCMV) infection develop sensorineural hearing loss (SNHL). However, the relationship between CMV load, SNHL and central nervous system (CNS) damage in cCMV infection remains unclear. This study aimed to examine the relationship between urinary CMV load, SNHL and CNS damage in newborns with cCMV infection. STUDY DESIGN: The study included 23 368 newborns from two maternity hospitals in Saitama Prefecture, Japan. Urine screening for cCMV infection (quantitative real-time PCR) and newborn hearing screening (automated auditory brainstem response (AABR) testing) were conducted within 5 days of birth to examine the incidence of cCMV infection and SNHL, respectively. CNS damage was assessed by MRI of cCMV-infected newborns. RESULTS: The incidence of cCMV infection was 60/23 368 (0.257%; 95% CI 0.192% to 0.322%). The geometric mean urinary CMV DNA copy number in newborns with cCMV was 1.79×106 copies/mL (95% CI 7.97×105 to 4.02×106). AABR testing revealed abnormalities in 171 of the 22 229 (0.769%) newborns whose parents approved hearing screening. Of these 171 newborns, 22 had SNHL (12.9%), and 5 of these 22 were infected with cCMV (22.7%). Newborns with both cCMV and SNHL had a higher urinary CMV DNA copy number than newborns with cCMV without SNHL (p=0.036). MRI revealed CNS damage, including white matter abnormalities, in 83.0% of newborns with cCMV. Moreover, newborns with CNS damage had a significantly greater urinary CMV load than newborns without CNS damage (p=0.013). CONCLUSIONS: We determined the incidence of cCMV infection and urinary CMV DNA copy number in seemingly healthy newborns from two hospitals in Saitama Prefecture. SNHL and CNS damage were associated with urinary CMV DNA copy number. Quantification of urinary CMV load may effectively predict the incidence of late-onset SNHL and neurodevelopmental disorders.

Age-related pathophysiological changes in rats with unilateral renal agenesis.

Affected rats of the unilateral urogenital anomalies (UUA) strain show renal agenesis restricted to the left side. To determine whether unilateral renal agenesis is a risk factor for the progression of renal insufficiency, we studied age-related pathophysiological alterations in affected rats. Although body growth and food intake were normal, polydipsia and polyuria with low specific gravity were present at 10 weeks and deteriorated further with age. Blood hemoglobin concentrations were normal, though there was slight erythropenia with increased MCV and MCH. Although hypoalbuminemia, hypercholesterolemia, azotemia, and hypermagnesemia were manifested after age 20 weeks, neither hyperphosphatemia nor hypocalcemia was observed. Plasma Cre and UN concentrations gradually increased with age. Cre clearance was almost normal, whereas fractional UN excretion was consistently lower than normal. Proteinuria increased with age, and albumin was the major leakage protein. In addition to cortical lesions, dilated tubules, cast formation, and interstitial fibrosis were observed in the renal medulla of 50 week-old affected rats. Renal weight was increased 1.7-fold and glomerular number 1.2-fold compared with normal rats. These findings show that the remaining kidney in UUA rats is involved not only in compensatory reactions but experiences pathophysiological alterations associated with progressive renal insufficiency.

[Diagnosis and management of urinary tract dilatations detected in utero]. / Diagnostic et prise en charge des dilatations des voies urinaires dépistèes in utero.

About 1% of the newborns show abnormalities of the urinary tract, representing 25% of the antenatally detected malformations. Most of these urinary abnormalities are detected by prenatal ultrasound between the 14th and the 22nd week of gestation. Their outcome is determined during the first weeks of pregnancy and depends on the degree of renal impairment and the presence of associated extrarenal malformations. Establishing the outcome is often difficult, however it can be predicted by ultrasound and biochemistry of fetal urine. Prenatal management should consist in follow-up and careful organisation of the postnatal management of congenital uropathies. Every antenatally dilated urinary tract requires postnatal investigation. Postnatal ultrasound on the 3rd to 4th day of life is recommended for confirming or excluding urinary abnormalities. In case of persistence, ultrasound has to be completed by other radiologic methods. Voiding cystourethrography and/or nuclear renography allow to identify the origin of the observed abnormalities. Apart from a few situations needing immediate correction, surgical treatment is rarely indicated. The principal of postnatal management is prevention of urinary tract infections by antibiotic prophylaxis and a close follow-up until adulthood.

[Panorama of uropathies discovered during the prenatal period. 147 cases]. / Panorama des uropathies dépistées en période anténatale. A propos de 147 observations.

OBJECTIVES: The aim of this study was to establish the panorama of uropathies discovered during the antenatal period and to analyze the explorations performed. Pregnancy outcome and infant prognosis was also recorded. METHOD: Ultrasonographic imaging revealed dilatation in 62.5% of the cases, parenchymal anomalies in 26.3% and unilateral or bilateral agenesia in 11.2%. The percentage of abnormal karyotypes was 4.76% for all urorenal symptomatologies. These abnormal karyotypes corresponded to 10% of those performed in 17 fetuses, urine puncture was used in order to assess in utero renal function. There were 113 live births, 31 medically termined pregnancies and 3 spontaneous abortions. Among the 113 live infants, 12 died during the post-natal period. Thirty-two infants were considered to be normal and 69 had an urorenal malformation, including 2 infants with pre-end-stage renal failure at 4 and 3 years. CONCLUSION: It is uncommon to discover an urorenal malformation at prenatal ultrasonography. The main problem is antenatal management and evaluation of prognosis. Urine puncture and in utero derivation are discussed. When no other reliable factors affecting fetal prognosis are available, puncture of fetal urine provides useful information for management although the technique remains under debate.

[Prognosis of prenatal uropathies: should fetal urine tests be continued?]. / Pronostic néphrologique des uropathies à révélation anténatale: faut-il continuer les ponctions d'urine foetale?

Twenty percent of the children with end stage renal failure have severe obstructive uropathies. The assessment of fetal renal function and the degree of renal damage in utero is a critical factor in providing realistic counseling. The prediction of postnatal renal function is made by sonography, fetal urinary biochemistry and fetal serum for beta-2-microglobulin. Ultrasonography is a useful method including assessment of amniotic volume and ultrasonographic evaluation of the renal parenchyma. The analysis of fetal urine for the assessment of renal function leads to conflicting results. Some papers conclude that fetal urine electrolytes are not an accurate predictor of neonatal renal function, others conclude that they provide useful information. The number of studies dealing with the urinary beta-2-microglobulin levels in the assessment of prenatal renal function is too small for allowing definitive conclusions. The predictive value of fetal serum beta-2-microglobulin for neonatal renal function may be interesting but the results are yet preliminary. The studies of fetal urinary biochemistry should be continued within prospective research programs; the data are either too conflicting or too preliminary to use this methodology in commun practise.

[Renal excretion of glycosaminoglycans under normal conditions and in several nervous system diseases in children]. / Pochechnaia ékskretsiia glikozaminoglikanov v norme i pri nekotorykh zabolevaniiakh nervoi sistemy u detei

The authors studied 101 children with diseases of the nervous system (with hereditary and acquired pathology) and 205 practically normal children. The urine excretion of specific components of the connective tissue (glycosaminoglycanes) was higher than in normals. Lesions of the connective tissue stroma in such forms of pathology is expressed not only in quantitative changes of glycosaminoglycane, but in their qualitative characteristics. Disturbances of the fractional compounds of glycosaminoglycane in the urine of patients differs from the parameters of chromatograms of normals by a high content of fractions of heparansulfate in a relatively low level of chondroethylsulfatolike fractions. In such states the severity of the clinical picture is accompanied by expressed metabolic disturbances.