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Background: Hypomagnesemia in patients with congenital anomalies of the kidneys and urinary tract or autosomal dominant tubulointerstitial kidney disease is highly suggestive of HNF1B-associated disease. Intriguingly, the frequency of low serum Mg 2+ (sMg) level varies and is lower in children than in adults with HNF1B mutations that could be partially due to application of inaccurate normal limit of sMg, irrespective of age and gender. We aimed to re-assess cross-sectionally and longitudinally the frequency of hypomagnesemia in HNF1B disease by using locally derived reference values of sMg., Methods: Fourteen children with HNF1B-associated kidney disease were included. Control group comprising 110 subjects served to generate 2.5th percentiles of sMg as the lower limits of normal., Results: In both controls and patients, sMg correlated with age, gender, and fractional excretion of Mg 2+ . In girls, sMg concentration was higher than in boys when analyzed in the entire age spectrum (p < 0.05). In HNF1B patients, mean sMg was lower than in controls as compared with respective gender- and age-specific interval (p < 0.001). Low sMg levels (< 0.7 mmol/l) were found in 21.4% of patients at diagnosis and 36.4% at last visit, which rose to 85.7% and 72.7% respectively when using the age- and gender-adjusted reference data. Similarly, in the longitudinal observation, 23% of sMg measurements were < 0.7 mmol/l versus 79.7% when applying respective references., Conclusions: Hypomagnesemia is underdiagnosed in children with HNF1B disease. sMg levels are age- and gender-dependent; thus, the use of appropriate reference data is crucial to hypomagnesemia in children.

Aim: The aim of the study was to investigate whether the functional IL10-1082A/G polymorphism exert a role in congenital anomalies of the kidney and urinary tract (CAKUT) in children. Also, the serum IL-10 and its association with genotype and renal parenchymal damage in CAKUT were explored., Methods: In the current case-control study, 134 paediatric cases of CAKUT and 382 unrelated controls were included. The genotyping of IL10-1082A/G polymorphism was performed by amplification refractory mutation system-PCR and IL-10 serum level was determined by ELISA., Results: Although, the genotype and allelic frequencies of IL10-1082 A/G polymorphism in cases and controls were similar (χ 2  = 0.459; P = 0.79 and χ 2  = 0.426; P = 0.51, respectively), significant different genotype distribution between patients with or without parenchymal damage/reduction was observed (χ 2  = 6.9; P = 0.032). The GG-genotype was more frequent in cases with renal parenchymal damage/reduction compared to patients with preserved parenchyma (22% vs. 9%; OR = 2.987; 95% CI = 0.979-9.468; P = 0.031). On the contrary, the heterozygous genotype was less frequent among cases with parenchymal damage/reduction compared to cases with preserved parenchyma (39% vs. 59%; OR = 0.453; 95% CI = 0.214-0.958; P = 0.024). Additionally, the serum IL-10 was significantly higher in CAKUT patients compared to age-sex-matched controls (median 11.98; IQR: 7.14-31.6 vs. 5.92; IQR: 4.68-14.8; P = 0.0057). Among carriers of GG-genotype significantly higher IL-10 level was detected in cases with parenchymal damage/reduction, than cases with preserved parenchyma (P = 0.028)., Conclusion: Our results suggested that the functional -1082A/G polymorphism in IL10 is associated with risk of renal parenchymal damage/reduction rather than genetic predisposition to CAKUT. Additionally, our study supposes that immunoregulatory cytokine IL-10 might have a significant role in CAKUT., (© 2018 Asian Pacific Society of Nephrology.)

Uterine torsion is a rare obstetric complication with a non-specific presentation. We describe a patient with a bicornuate uterus and a pregnancy complicated by a markedly elevated second-trimester maternal serum alpha-fetoprotein (MSAFP), intermittent pelvic pain and fetal growth restriction. At 24 weeks gestational age, she presented to labour and delivery with an acute abdomen. A subsequent exploratory laparotomy revealed torsion and rupture of her right uterine horn. Uterine torsion can be difficult to diagnose because it is not associated with specific symptoms or characteristic imaging findings. In patients with a bicornuate uterus who present with abdominal pain, an elevated mid-trimester MSAFP may be a harbinger of placental ischaemia as a result of uterine torsion., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Aim: The aim of this study was to investigate the association of an insertion/deletion (I/D) polymorphism in angiotensin-converting enzyme (ACE) gene with serum ACE level in relation to the type and severity of malformations from congenital anomalies of the kidney and urinary tract (CAKUT) spectrum., Methods: A group of 134 Bulgarian children with CAKUT divided into four subgroups according to the leading malformation and 109 controls were genotyped by classical polymerase chain reaction. The quantitative determination of serum ACE was performed by ELISA method., Results: A significant elevation of DD-genotype was observed in high-grade hydronephrosis compared to low-grade (43% vs. 9%). The carrying of DD-genotype was associated with higher risk for severe hydronephrosis with OR = 7.5 (95% CI: 1.242÷45.278; P = 0.028). Also, elevated serum ACE concentrations in patients with high-grade compared to low-grade hydronephrosis (237.4 ± 45 ng/mL vs 180.5 ± 64 ng/mL; P = 0.0065) were found. ACE level was significantly lower in patients with unilateral renal agenesis; hypo/dysplasia and multicystic dysplastic kidney (156.6 ± 54 ng/mL) than controls (200.6 ± 56.7 ng/mL; P = 0.005) and the remaining CAKUT subgroups., Conclusion: The DD genotype of I/D ACE polymorphism encodes the highest serum ACE level may be an additional genetic risk factor contributing to the severe hydronephrosis in Bulgarian patients with obstructive uropathies in contrast to other investigated categories of CAKUT malformations., (© 2016 Asian Pacific Society of Nephrology.)

Prochloraz is an imidazole fungicide, and its regulatory toxicological data package has been primarily generated in the 1990s. More recently, studies have been published demonstrating an interaction with hormone receptors/steroidogenesis and effects with an endocrine mode of action. In the present study, prochloraz has been investigated in a comprehensive in vivo study including relevant elements of current regulatory reproduction toxicity studies and additional mechanistic parameters. Prochloraz was administered per gavage in oil from GD 6 to PND 83 to pregnant and lactating Wistar rats and their respective offspring, at doses of 0.01 mg/kg bw/day (acceptable daily intake of prochloraz), 5 mg/kg bw/day [expected no-observed-effect-level (NOEL)] and 30 mg/kg bw/day. At 30 mg/kg bw/day maternal and offspring effects (decreased viability, lower number of live offspring) were seen including a delayed entry into male puberty (+1 day) accompanied by lower male offspring body weights, increased anogenital distance/index in females and transiently retained nipples in males at PND 12 (not seen at PND 20). The only finding at the "expected NOEL" was increased incidences of transiently retained nipples in males which are not considered adverse. No effects were seen in the low-dose group. There was no evidence for a non-monotonic dose-response curve or effects at low levels.

Introduction: Although mortality has decreased for fetuses with lower urinary tract obstruction treated with vesicoamniotic shunt (VAS) placement, survivors remain at risk for long-term renal impairment. We tested the association of fetal serum β2-microglobulin (fsβ2M) with postnatal renal function in these patients, hypothesizing that fsβ2M may predict such renal impairment., Materials and Methods: fsβ2M was obtained in patients undergoing VAS placement. The primary outcome was renal function at 3-12 months of life, as assessed by a pediatric nephrologist using medical records. Patients were divided into two groups: (1) 'stable renal function' - probable stable long-term renal function and reasonable growth - and (2) 'loss of renal function' - early loss of renal function and failure to thrive., Results: Nineteen patients with preoperative fsβ2M received a VAS. Of the 14 survivors, those with fsβ2M ≤5.6 mg/l tended to have stable renal function compared to those with fsβ2M >5.6 mg/l [5/6 (83.3%) vs. 2/8 (25.0%), OR = 15.00, 95% CI 0.70-709.89; p = 0.1026]. Eight of 9 patients followed for >12 months of age had outcomes consistent with the initial renal assessments., Discussion: Patients with initial fsβ2M >5.6 mg/l and treated with VAS tended to have poor renal outcomes., (© 2016 S. Karger AG, Basel.)

Dichlorodiphenyltrichloroethane (DDT) is used for malaria control by 10 countries, nine of which are in Africa. Technical DDT contains various isomers with 65-80% insecticidal p,p'-DDT and 15-21% o,p'-DDT, an estrogenic chemical, while the persistent metabolite of p,p'-DDT, dichlorodiphenyldichloroethylene (p,p'-DDE), is an antiandrogen. In utero antiandrogenic exposure reduces anogenital distance in animal models and the anal position index in a single study. This study examined the associations between mother's serum DDT and DDE levels at delivery and anogenital distance in their children at birth and age 1 year. Data were collected as part of the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE), a birth cohort study located in rural South Africa. DDT and DDE concentrations were measured in blood samples collected from 752 mothers at delivery. Anogenital distance measurements, taken at birth (n = 671) and age 1 year (n = 674), included anofourchette and anoclitoral distances in girls, and anoscrotal and anopenile lengths in boys. We also measured anococcygeal and coccyx-fourchette distances in girls, while in boys, we measured anococcygeal and coccyx-scrotal distances as well as penile length and penile width. The anal position index is calculated for both sexes as anoscrotal/coccyx-scrotal in boys and anofourchette/coccyx-fourchette in girls. We found no associations between p,p'-DDT/-DDE or o,p'-DDT and anogenital distance measurements at birth in either boys or girls. At 1 year, o,p'-DDE was negatively associated with anofourchette in girls (β =-1.32 mm, 95% confidence interval (CI) = -2.27, -0.38) and positively associated with penile width in boys (β = 0.30 mm, 95% CI = 0.00, 0.60). The results do not suggest an overt antiandrogenic or estrogenic effect on anogenital distance after long-term DDT exposure. These weak associations may be due to chance., (© 2016 American Society of Andrology and European Academy of Andrology.)

Background: Although renal inulin clearance (Cin) is the gold standard for evaluation of kidney function, it cannot be measured easily. Therefore, creatinine clearance (Ccr) is often used clinically to evaluate kidney function. Enzymatically measured Ccr was recently found to be much higher than Cin because of the tubular secretion of creatinine (Cr). This study compared three measures of renal clearance, inulin, 2-h Ccr, and 24-h Ccr, in children., Methods: Kidney function was evaluated in 76 children (51 males and 25 females) aged 1 month to 18 years with chronic kidney disease (CKD) by three renal clearance methods at almost the same time., Results: Correlations between each pair of three renal clearance measurements were determined. Approximate glomerular filtration rate (GFR) was equal to 62 % of 2-h Ccr or 76 % of 24-h Ccr., Conclusion: Cr secretion by renal tubules was approximately 50 % of the GFR. In this study, we indicate that the measurements of 2-h Ccr or 24-h Ccr do not show true GFR but we could infer approximate GFR from the values. The use of 2- or 24-h Ccr might contribute to the treatment of pediatric CKD patients.

Objective: Compensatory hypertrophy has been classically described in patients with monorchidism. However, it remains unclear whether there is a functional compensatory activity of the different cell populations. Our aim was to assess the functional capacity of the solitary testis in monorchid males from infancy through puberty in order to determine whether the remaining gonad is capable of compensating the functional activity of Sertoli and Leydig cells of the absent gonad., Design: In a retrospective, cross-sectional, analytical study performed at a tertiary paediatric public hospital, we included 89 boys with monorchidism and 358 healthy controls, aged 6 months-18 years. Testicular volume and circulating levels of reproductive hormones were compared between patients with monorchidism and normal boys. Serum anti-Müllerian hormone (AMH) and FSH were used as biomarkers of the functional mass of prepubertal Sertoli cells, whereas serum testosterone and LH were used as biomarkers of Leydig cells., Results: In the vast majority of the cases, the testicular volume of monorchid boys was smaller than the sum of the volume of both testes of healthy controls. Serum AMH was lower and FSH was higher in patients with monorchidism than in controls aged <3 and >13 years. Serum testosterone and LH did not differ significantly between patients and controls., Conclusion: In boys and adolescents with monorchidism, there is a dissociated capacity of the remaining testis to compensate for the absence of the other gonad: while Leydig cell function is largely compensated, Sertoli cell proliferation and function was lower than in controls., (© 2016 European Society of Endocrinology.)

Objective: To describe the profile of patients with genitourinary abnormalities treated at a tertiary hospital genetics service., Methods: Cross-sectional study of 1,068 medical records of patients treated between April/2008 and August/2014. A total of 115 cases suggestive of genitourinary anomalies were selected, regardless of age. A standardized clinical protocol was used, as well as karyotype, hormone levels and genitourinary ultrasound for basic evaluation. Laparoscopy, gonadal biopsy and molecular studies were performed in specific cases. Patients with genitourinary malformations were classified as genitourinary anomalies (GUA), whereas the others, as sex differentiation disorders (SDD). Chi-square, Fisher and Kruskal-Wallis tests were used for statistical analysis and comparison between groups., Results: 80 subjects met the inclusion criteria, 91% with SDD and 9% with isolated/ syndromic GUA. The age was younger in the GUA group (p<0.02), but these groups did not differ regarding external and internal genitalia, as well as karyotype. Karyotype 46,XY was verified in 55% and chromosomal aberrations in 17.5% of cases. Ambiguous genitalia occurred in 45%, predominantly in 46,XX patients (p<0.006). Gonadal differentiation disorders accounted for 25% and congenital adrenal hyperplasia, for 17.5% of the sample. Consanguinity occurred in 16%, recurrence in 12%, lack of birth certificate in 20% and interrupted follow-up in 31% of cases., Conclusions: Patients with SDD predominated. Ambiguous genitalia and abnormal sexual differentiation were more frequent among infants and prepubertal individuals. Congenital adrenal hyperplasia was the most prevalent nosology. Younger patients were more common in the GUA group. Abandonment and lower frequency of birth certificate occurred in patients with ambiguous or malformed genitalia. These characteristics corroborate the literature and show the biopsychosocial impact of genitourinary anomalies., (Copyright © 2015 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.)

Background: The normal relationship between the scrotum and penis during fetal development is controlled by several genetic and hormonal factors, and impairment of this positional relation results in a wide spectrum of positional congenital anomalies., Objective: This a cohort study analysing 63 cases of penoscrotal anomalies (PSAs) according to severity and other associated malformations to provide a simple classification for recognising, describing and categorizing cases that may require surgical correction., Design and Setting: Between 2005 and 2013, 63 diverse cases of penoscrotal positional anomaly were detected and analysed based on their hormonal profile and other associated anomaly., Results: A wide variety of PSAs were included in the study, 11 cases were of major PST with complete penoscrotal transposition in three, incomplete in eight, and minor degree in 45 cases, which are symmetrical (bilateral) in 29, sixteen are asymmetrical, 4 had midline scrotlisation, and 3 had wide penoscrotal distance. Associated genitourinary anomalies were detected in 29 babies. Sex hormonal assays showed no significant differences between the PSA patients and controls (P < .05), and no gross chromosomal anomalies were detected in any cases., Conclusion: Penoscrotal positional anomalies include the previously described penoscrotal transposition, and the variants of a central penile scrotalisation, and wide penoscrotal distance. A simple classification for these anomalies adopted herein., (Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.)

In a context of foetal obstructive uropathies, biochemical markers can be helpful to assess the renal function, but most studies to date have focused on their correlation with ultrasound findings and neonatal outcome. Our aim was to evaluate foetal β2-microglobulin as an index of histological injury to the kidney. β2-microglobulin was measured in serum and/or urine from 27 foetuses with bilateral obstructive uropathy, and compared to the findings of kidney examination following the termination of pregnancy. In serum, increased β2-microglobulin levels correlated to a decreased number of glomeruli, a reduction in the blastema and the presence of primitive ducts reflecting renal hypoplasia and dysplasia. However, elevated β2-microglobulin levels in the urine correlated only to a decreased number of glomeruli., (Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Objective: To compare the prognostic value of fetal serum α1-microglobulin with that of β2-microglobulin and cystatin C for postnatal renal function., Method: Retrospective study of α1-microglobulin, β2-microglobulin, and cystatin C in fetal serum from 126 fetuses with congenital abnormalities of the kidney and urinary tract (73 and 53, respectively). Two groups were defined: group with normal renal function and group with renal failure. For live born infants, renal function was assessed on the basis of serum creatinine (cutoff 50 µmol/L) or glomerular filtration rate (cutoff 75 mL/min/1.73 m2) or both. In case of infant or fetal death, histological kidney lesions were considered., Results: Significant differences (p < 0.001) were observed for the three markers between fetuses with good renal prognosis and those with renal failure (34.4 mg/L vs 67.6 mg/L for α1-microglobulin, respectively; 3.9 mg/L vs 7.35 mg/L, for β2-microglobulin, respectively; and 1.67 mg/L vs 2.12 mg/L for cystatin C, respectively). Areas under receiver operator curves were used to compare the three markers, 0.96, 0.90, and 0.74 for β2-microglobulin, α1-microglobulin, and cystatin C, respectively., Conclusion: Although α1-microglobulin is significantly different in fetuses with good renal prognosis and those with renal failure, overall, it is a less reliable prognostic marker than fetal serum β2-microglobulin., (© 2013 John Wiley & Sons, Ltd.)

Objectives: Congenital anomalies have been inconsistently associated with maternal crude estimated exposure to drinking water trihalomethane (THM). We investigated the relationship between individual THM uptake during the first trimester of pregnancy and congenital anomalies., Methods: We estimated maternal THM uptake for 3074 live births using residential tap water concentrations, drinking water ingestion, showering and bathing, and uptake factors of THM in the blood. Multiple logistic regression was used to investigate the association of THM exposure with congenital anomalies., Results: We observed no statistically significant relationships between congenital anomalies and the total THM internal dose. We found little indication of a dose-response relationship for brominated THM and congenital heart anomalies. The relationship was statistically significant for bromodichloromethane (BDCM) (OR=2.16, 95% CI 1.05 to 4.46, highest vs lowest tertile) during the first month of pregnancy. During the first trimester of pregnancy, the probability of developing heart anomalies increased for every 0.1 μg/d increase in the BDCM and for every 0.01 μg/d increase in the internal dibromochloromethane (DBCM) dose (OR 1.70, 95% CI 1.09 to 2.66, and OR 1.25, 95% CI 1.01 to 1.54, respectively). A dose-response relationship was evident for musculoskeletal anomalies and DBCM exposure during the first and second months of pregnancy, while BDCM exposure tended to increase the risk of urogenital anomalies., Conclusions: This study shows some evidence for an association between the internal dose of THM and the risk of congenital anomalies. In particular, increased prenatal exposure to brominated THM might increase the risk of congenital heart and musculoskeletal anomalies.

Objectives: The incidence of acute kidney injury in neonates is high and associated with up to a 50% mortality rate. The purpose of this review was to determine the feasibility of using serum cystatin C measurements to assist clinicians in making early and accurate diagnoses of acute kidney injury in neonates., Data Source: We searched for the following seven key words within the PubMed database and the Cochrane Database of Systematic Reviews: cystatin C, neonates, newborn, preterm, premature, kidney failure, and kidney injury., Study Selection: The selected studies included neonates within their study populations and were published in English. We reviewed literature published between January 1990 and May 2012., Data Extraction: Ten studies had conducted serum cystatin C measurements in neonates., Data Synthesis: The cystatin C level in neonates is not influenced by the maternal level and is highest at birth. In most studies, cystatin C levels on day 1 of life ranged between 1 and 2 mg/L, gradually declined during the first year and then remained relatively stable thereafter. Cystatin C levels did not differ between male and female infants, and no significant gestational age-dependent differences were found. Cystatin C levels were increased in cases of sepsis, acute kidney injury, and congenital renal abnormalities., Conclusions: Cystatin C has all of the theoretical properties needed to be an ideal marker of renal function. It can be used to determine baseline renal function on day 1 and is increasingly being used to determine renal function in sick neonates. In the majority of studies, the day 1 cystatin C level ranged between 1 and 2 mg/L, which gradually declined in the first year of life. However, the number of available studies evaluating cystatin C in sick neonates is currently limited, and there are also no studies linking cystatin C levels in sick babies with short-term and long-term outcomes.

The aim of the study was to assess serum cystatin C level in children with a congenital solitary kidney, depending on their age and compensatory overgrowth of the kidney. The study group (I) consisted of 36 children, 3-21 years of age (median 10.8 years), with a congenital solitary kidney and no other urinary defects. The control group (C) contained 36 healthy children, 5-21 years old (median 10.9 years). Nephelometric methods were used to determine serum cystatin C level, the Jaffe method to assess creatinine concentration and the Schwartz formula to estimate glomerular filtration rate. Kidney length was measured with the patient in a supine position, and overgrowth was estimated (O%) in comparison with the respective kidney in the control group. Serum cystatin C level in group I was higher than that in the control group (P<0.05). Increased values, above 0.95 mg/l, were found in 16/36 (44%) children aged 12-21 years. Glomerular filtration rate (GFR, estimated by the Schwartz formula) and creatinine level in group I were similar to those of the control group (P>0.05). Increased kidney length was found (median 18.2%). Cystatin C concentration was positively correlated with O% (r=0.406, P<0.01) and kidney length to child height ratio (L/H) (r=0.376, P<0.05). We conclude that Increased serum cystatin C concentration in patients with a unilateral congenital solitary kidney occurs after 12 years of age and correlates with compensatory overgrowth of the kidney.

Reduced fetal growth is known to be associated with a reduced ovarian fraction of primordial follicles, with ovarian hyperandrogenism and anovulation in late adolescence. In this study, we examined whether adolescent girls born small for gestational age also present an abnormality in uterine or ovarian size. Standardized ultrasound measurements of the internal genitalia were performed in 36 healthy post-menarcheal girls (mean age 14 y) born with a size that was either appropriate for gestational age (AGA) or small (SGA), birth weight averaging 0.1 and -3.0 SD, respectively; clinical and endocrine characteristics were documented concomitantly. Compared with AGA girls, the SGA girls had a smaller uterus (mean difference of 20%; p < 0.006) and a reduced ovarian volume (mean difference of 38%; p < 0.0002). In conclusion, the gynecological correlates of prenatal growth restriction are herewith extended to include a reduced size of the uterus and the ovaries.

Purpose: Although the prepubertal immune system cannot recognize postmeiotic germ cell antigens, an overall 21 to 28% incidence of antisperm antibodies directed at these antigens has been reported preoperatively in prepubertal children with cryptorchidism and other inguinoscrotal anomalies. We investigated the prevalence of antisperm antibodies in these prepubertal patients before and after surgery., Materials and Methods: We examined 82 prepubertal boys 0.6 to 13.2 years old, including 33 with unilateral cryptorchidism, 21 with inguinoscrotal anomalies and 28 who were normal. IgG, IgM and IgA antisperm antibodies were determined by the indirect Immunobead test. Serum testing was repeated 1 and 2 years postoperatively and annually for 2 more years in the normal children. Also sera from 183 infertile men 21 to 47 years old with a history of cryptorchidism and/or inguinal hernia operated on in childhood were similarly studied., Results: Of the adults 70 (39%) tested IgG positive, including 12 (7%) who were also IgA positive, and all tested IgM negative. Repeat measurements were negative for all IgG, IgA and IgM isotypes in all children, patients and controls., Conclusions: We conclude that there are no antibodies to sperm surface antigens in prepubertal children with cryptorchidism and inguinoscrotal anomalies before and within 2 years after surgery. Autoimmunity against postmeiotic sperm membrane antigens is apparent in adults only.

Abnormalities were detected in 2669 of 326,257 elementary and junior high school children (169,856 males and 156,401 females) who were screened at school for urinary abnormalities. Serum complement (C3) level was measured in all 2669 children having urinary abnormalities (811 males, 1856 females). Three had a serum C3 level that was more than three standard deviations below the mean value. Type I membranoproliferative glomerulonephritis (MPGN) was diagnosed on histological examination in one of these three children, while the other two did not undergo renal biopsy because they had serum C3 levels of 40 and 44 mg/dL, respectively, and because their urinary abnormalities were transient. It was considered that there is not much significance in testing the serum complement in the urine screening done at school and the cost/benefit ratio is low. The results appeared to reflect the frequency of persistent hypocomplementemic MPGN in Japan in recent years.