Uropathy Research Articles

Carcinoma of the lower female genital tract in patients with genitourinary malformations: a clinicopathologic analysis of 36 cases

Background: Lower genital tract carcinomas that coexist with genitourinary malformations are rare. The aim of this study was to investigate the clinicopathologic characteristics and outcomes of patients with this rare joint condition. The aim of this study was to investigate the clinicopathologic characteristics and outcomes of these patients to analyze the associations among clinicopathologic features in this rare entity.Methods: The medical records of patients with carcinoma of lower genital tract combined with genital tract malformations who were treated at Peking Union Medical College Hospital (Beijing, China) between January 1995 and December 2017 were retrospectively reviewed and a comprehensive literature review was performed. The correlations between variables were determined using Fisher's exact test.Results: Thirty-six patients were identified, among whom 22 had cervical carcinoma, 10 had vaginal carcinoma, and two had carcinomas of both the cervix and vagina. The most common genital tract anomaly was uterus didelphys (n=17), and 63.9% of patients had with urinary tract malformations. Twenty-five (69.4%) had pathologically confirmed adenocarcinoma, 10 (27.8%) had squamous cell carcinoma (SCC), and 1 had adenosquamous carcinoma. Patients with urinary tract malformations developed adenocarcinoma more frequently than those without malformations (95.7% vs. 30.8% P<0.001). Compared with patients with SCC, patients with adenocarcinoma presented at a younger age (36.1 vs. 47.0 years, P=0.011), had more advanced stages disease (57.7% vs. 10.0% were in stage II-IV, P=0.022), and tended to have poorer five-year overall survival rates (75.6% vs. 100.0%, P=0.279).Conclusions: Patients with simultaneous malformations of the genital and urinary tracts had a high probability of developing adenocarcinoma. It is recommended that rigorous gynecologic exams with Pap smears and imaging analyses be performed periodically in women with genital malformations, as they may be at a risk of genital malignancies.

Growth of pediatric recipients after renal transplantation from small pediatric deceased donors weighing less than 15kg.

RTx is currently the best treatment for children with ESRD. This study retrospectively analyzed the outcomes of growth after RTx using the pediatric-to-pediatric allocation strategy and some factors that may affect it. From March 2012 to August 2016, 8 en bloc and 38 single pediatric RTxs were performed at our center using organs from small pediatric deceased donors (weight<15kg). Growth before and after RTx was analyzed according to the height-for-age z-score at RTx, the 3-year follow-up, and adulthood and compared between the procedures. The chi-square test and multiple linear regression analysis were used for statistical analyses. Overall, 79.2% of children were diagnosed with chronic nephritis before RTx; 14.6% of cases were due to congenital urinary tract malformation, and 6.3% of cases were due to unknown causes. All grafts and patients survived postoperatively. The mean estimated GFRs were 92.7±28.6mL/min/1.73m2 , 100.9±32.3mL/min/1.73m2 , and 110.1±34.8mL/min/1.73m2 at 1, 2, and 3years' postoperatively, respectively. The children's postoperative growth and development, particularly during the first year postoperatively, improved but were negatively correlated with age and the height-for-age z-score before RTx. The growth of children after RTx was moderate and accelerated during prepubescence. The rate of post-RTx growth during the first year postoperatively was unrelated to the recipient's sex or duration of dialysis (P>0.05) but was negatively correlated with age at RTx (r=-0.349, P=0.043). Future studies on the long-term outcomes are still needed.

Urine collection methods used for non-toilet-trained children in pediatric emergency departments in France: A medical practice analysis

IntroductionSince April 2015, the French Society of Pediatrics has encouraged suprapubic aspiration (SA) and urethral catheterization (UC) for urine collection in non-toilet-trained children suspected of having urinary tract infections (UTIs) and has tried to reduce the use of urine bag (UB). ObjectiveTo analyze the medical practices concerning urine collection methods used for non-toilet-trained children in pediatric emergency departments in France. MethodsWe conducted a descriptive medical practice study in October 2017. All members of the French Society of Pediatric Nephrology received two questionnaires about urine collection methods used for non-toilet-trained children, distinguishing between male and female patients, and about the corresponding analgesic protocols used in their pediatric emergency departments. ResultsIn total, 26 centers completed questionnaires concerning female patients. UC was performed in cases of fever associated with urinary tract malformations in 14 of 26 centers (54%). UB was used in cases of fever of unknown origin lasting for more than 48h in 17 of 26 centers (65%), in cases of fever associated with UTI symptoms in 14 of 26 centers (54%), and in cases of fever in infants under 3 months of age in 16 of 26 centers (61%). The questionnaires concerning male patients were completed by 30 centers. UB was the initially used urine collection method in all situations with, respectively, 22 of 30 (73%), 27 of 30 (90%), 23 of 30 (77%), and 22 of 30 (73%) centers. The analgesic protocol for urine collection is not well established in France. ConclusionUC for urine collection in pediatric emergency departments in France is underused despite the national recommendations and the greater diagnostic power of this method compared with UB.

Epidemiology of Urinary Tract Infection in Neonatal Intensive Care Unit of Mohammed VI University Hospital in Marrakech

Objective:The objective of our study is to estimate the extent of urinary infection among neonatal infectious diseases.Materials and Methods:This work concerns a retrospective study of 91 newborns with urinary tract infections, collected in the Mohammed VI neonatal resuscitation unit, Marrakesh.Results:The average age of our newborns at admission was 10.8 days. In 20 cases, there were signs of maternal urinary tract infections. The main reason for hospitalization was jaundice in 72.53% of cases. The symptomatology was dominated by fever in 16.48% of cases, followed by a refusal to suck in 5.5% of cases.Escherichia coliwas the predominant germ in 61.5% of cases. A probabilistic anti-biotherapy based on Ceftriaxone 3rdGeneration and aminoglycoside was instituted in all cases after it was adapted to the antibiogram data. Ultrasound revealed malformations in 21 cases.Conclusion:Neonatal urinary tract infection remains a common pathology. Its potential severity involving renal functional prognosis and the frequency of urinary tract malformations require early diagnosis and adequate management.

Role of Calcium to Citrate Ratio in Predicting Stone Formation in Idiopathic Hypercalciuria Children (2-12 Years Old)

Considering the predictive role of the relatively low urinary citrate for stone formation, especially in hypercalciuric patients, this study is aimed at comparing urine calcium to citrate (Ca/Cit) ratio in 3 groups of children, including patients with idiopathic hypercalciuria with and without renal stone as well as the healthy children. This study was carried out on 96 children (2 to 12years old) referred to a pediatric nephrology clinic in the city of Ahvaz, Southwest Iran. All the children underwent renal ultrasonography, urinalysis, and measurement of random nonfasting urine Ca, Cr, and citrate. Those with secondary hypercalciuria, urinary tract malformations, and/or functional abnormalities of the gastrointestinal tract were excluded from the study. The mean Ca/Cit. ratio (mg/mg) in the three groups, including children with hypercalciuric with and without renal stones and the healthy children (control group), was 0.44±0.14, 0.39±0.13, and 0.19±0.08, respectively, which showed a significant difference (P<.001). There was also a significant difference in Ca/Cit ratio between the first and the control group by Tukey's range test (P<.001). Mean urinary Ca/Cit ratio in those with a positive family history of urolithiasis within three groups was 0.42±0.17 and in those with a negative family history was 0.32±0.16 (P=.013). Mean Ca/Cit. ratio (mg/mg) of 0.25 showed a sensitivity of 90.6% (confidence interval: 75.7-96.7%) and a specificity of 81.2% (confidence interval: 64.7-91.1%) to differentiate between the renal stone group and the control group. High Ca/Cit ratio can predict stones formation in hypercalciuric patients, especially in those with a positive family history of urolithiasis. The present study found the cutoff level of 0.25 for Ca/Cit. ratio as the highest prognostic value for renal stone formation.

A rare case of fibroadenoma in ectopic breast tissue of axilla: case report

Developmental abnormalities of breast can lead to formation of ectopic breast tissue which may present as polymastia or polythelia or in form of swelling along the milk line. Ectopic breast tissue can also develop pathological changes similar to normal located breast tissue. This report is about a case of fibroadenoma developing in ectopic breast tissue of axilla. A thirty-four-year-old female presented with painful swelling in right axilla for 2 years and was diagnosed with fibroadenoma of axillary tail of right breast. Excision biopsy of the swelling confirmed the diagnosis of fibroadenoma. Fibroadenoma must be considered for any axillary swelling along with other differential diagnoses like lymphadenopathy, carcinoma arising from ectopic breast tissue, lipoma, sebaceous cyst, tuberculosis, vascular lesions, cutaneous malignancies or secondaries in lymph nodes. Ectopic breast tissue should be subjected to similar evaluation and screening as is recommended for normally located breast tissue. The patient should also be evaluated for possibility of kidney and urinary tract malformations.

Research status of congenital renal and urinary tract malformation in children

Congenital abnormalities of the kidney and urinary tract (CAKUT)is caused by a variety of reasons, with various phenotypes characterized by congenital anatomic abnormalities of urinary system, and the rate of occurrence is high.CAKUT is the main cause of chronic kidney disease in children, and some patients can progress to end-stage renal disease(ESRD). The study of CAKUT in children is of great significance to eugenics, and its pathogenesis is not completely clear.However, many studies have proved that the pathogenesis of CAKUT is related to many factors, such as gene mutation, copy number variation and environment.In addition, the use of color doppler ultrasonography has a significant advantage in the discovery of children′s CAKUT.It is the first choice for screening, and then the early corresponding treatment intervention will greatly reduce the degree of damage to the renal function of the children and improve the survival rate of the children, which is of great significance for the prevention of disease.We reviewed the epidemiological studies, etiological studies, color doppler ultrasound screening and interventive treatment of children with CAKUT in recent years, in order to make pediatricians understand children′s CAKUT more comprehensively, and take active intervention measures to delay the progress of CKD and prevent the occurrence of ESRD. Key words: Congenital abnormalities of the kidney and urinary tract; Screening; Etiology; Chidren; Intervention

Reflux nephropathy and the risk of preeclampsia and of other adverse pregnancy-related outcomes: a systematic review and meta-analysis of case series and reports in the new millennium.

Reflux nephropathy is a common urinary tract malformation, and a substantial cause of morbidity in women of childbearing age. While recent studies provide further new information on pregnancy-related outcomes, their results are heterogeneous and a systematic meta-analysis may help the interpretation. The aim of this review was to analyze pregnancy-related outcomes in the recent literature on reflux nephropathy (2000-2016), to perfect the estimation of risks, and to identify specific research needs. We searched Medline, EMBASE and the Cochrane review databases for the period 2000-2016 (PROSPERO registration no. 42016042713). all case series and case reports dealing with reflux nephropathy and reporting on at least one pregnancy outcome. Data were extracted from eligible case series (≥ 6 cases). For the outcomes preeclampsia (PE), pregnancy-induced hypertension (PIH), preterm birth, and newborns small for gestational age, we employed as a control group the low-risk pregnancies from a multicenter database including 1418 live-born singletons. Case reports were analyzed narratively. The search retrieved 2507 papers, of which 7 case series and 4 case reports were retained. The series report on 434 women with 879 pregnancies; no study reported controls. Compared to the low-risk controls, the meta-analysis showed an increased risk of PIH (odds ratio, OR 5.55; confidence interval, CI 3.56-8.66), PE (OR 6.04; CI 2.41-15.13), and all hypertensive disorders combined (OR 10.43; CI 6.90-15.75). No difference was observed in preterm delivery and caesarean sections. A higher incidence of stillbirth was reported in one paper. Conversely, the 4 case reports (on 10 pregnancies) alert us to a potentially severe complication, hydro(uretero)nephrosis with or without infection. Reflux nephropathy is associated with an increased risk of PIH and PE, but not of preterm delivery, suggesting the occurrence of late 'maternal' PE. The finding of a higher incidence of stillbirths in one series requires further analysis. Strict follow-up of these women is needed, in particular in late pregnancy stages, to avoid and manage in particular hypertensive pregnancy complications.

Urolithiasis in the pediatric population - current opinion on epidemiology, patophysiology, diagnostic evaluation and treatment.

Urolithiasis, a condition in which calculi are found in the urinary tract, has been known for centuries. Although the disease was considered casuistic in the pediatric population, its prevalence is rising among both children and infants. The occurrence of the disease is greater in developed countries, therefore urolithiasis should be considered a lifestyle disease. Its etiopathogenesis has not yet been well understood. Kidney stone formation is influenced by factors such as climate, eating habits, profession, fluid intake, genetic predisposition, urinary tract infections and malformations of the urinary tract. Calculi are usually composed of mixed mineral substances. Only about 30% are made up of one chemical substance, calcium oxalate being the most common. Urolithiasis can be asymptomatic and accidentally diagnosed. Abdominal pain is the most common clinical symptom, however disease presentation among infants is nonspecific. Hematuria is a common clinical finding. Ultrasonography is the most important diagnostic tool in the diagnosis of kidney stone disease. Metabolic evaluation is required in every case of urolithiasis in the pediatric population, as metabolic disorders can be found in the majority of cases in this age group. The spontaneous passage of calculi less than 6mm in diameter is likely. Invasive treatment should be carried out if stones exceed 6mm in diameter or fail to expulse spontaneously. Prophylactic treatment includes adequate fluid intake, healthy eating habits and physical activity to maintain a healthy weight. Urolithiasis is a recurrent disease, therefore long-term treatment, prophylaxis and a lasting change in dietary habits are essential.

Pelvic floor dysfunction in the immediate puerperium, and 1 and 3 months after vaginal or cesarean delivery.

To identify and assess postpartum pelvic floor dysfunction (PFD) between vaginal delivery, elective cesarean delivery (ECD), and intrapartum cesarean delivery (ICD). The present prospective observational study included women aged at least 18years with no history of pelvic surgery or lower urinary tract malformation, and who had not undergone pelvic floor muscle (PFM) training in the preceding 12months, who underwent delivery at Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil between August 1, 2016, and May 31, 2017. Participants were assessed at 48hours (phase 1), 1month (phase 2), and 3months (phase 3) after delivery. Assessments included the International Consultation on Incontinence Questionnaire, Short Form (ICIQ-SF); the Jorge-Wexner anal incontinence scale; a self-rated visual analog scale for pelvic pain; the pelvic organ prolapse quantification (POP-Q) system; and a PFM perineometer. A total of 227 women were assessed in phase 1 (141 vaginal deliveries; 28 ICDs; and 58 ECDs), 79 in phase 2, and 41 in phase 3. The ICIQ-SF, Jorge-Wexner scale, visual analog scale, and perineometer measurements did not identify significant differences in relation to the type of delivery (P>0.05). The type of delivery was not associated with differences in the short-term development of postpartum PFD.

Are Congenital Urinary Tract Abnormalities Linked to Maternal Methylenetetrahydrofolate Reductase Polymorphisms in Fetuses of Intentionally Terminated Pregnancies with Oligo- or Anhydramnios ?

ABSTRACTObjective: We aimed to evaluate fetuses of terminated pregnancies with oligo-or anhydramnios (OAH) to further investigate the association between maternal methylenetetrahydrofolate reductase (MTHFR) polymorphisms and fetal urinary tract malformations. Materials and Methods: This retrospective study included 16 pregnancies with OAH (with normal fetal karyotype) that were intentionally terminated before 22nd gestational week. Fetal autopsy was performed in all cases. We evaluated cases for presence of DNA methylation pathway-related gene polymorphisms. Results: We demonstrated that renal abnormalities and disorders exist in 75% of the cases. Pulmonary system anomalies and single umbilical artery were the most frequently observed associated abnormalities. Polymorphisms with known reduced MTHFR activity were found in 81.8% (9/11) of the cases.Association between urinary system abnormalities and polymorphisms with known reduced MTHFR activity was observed in 88.8% (8/9) of the cases. Conclusion: Physicians should keep in mind that polymorphisms with known reduced MTHFR activity may be associated with urinary tract abnormalities and OAH.

Prune belly syndrome: a South African perspective

Background: Prune belly syndrome (PBS) is a rare congenital disorder with a triad of signs: absent abdominal wall musculature, urinary tract malformations, and cryptorchidism. The aims of this study were to describe the epidemiology, renal function, management and outcome of patients with PBS at the Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa. Methods: A retrospective record review was conducted of patients with PBS referred to the paediatric nephrology unit from 1984 to 2014. Results: A total of 44 patient records were analysed. Most of the patients presented as neonates (n = 35, 80%). The accompanying congenital malformations included urological problems (21, 48%), orthopaedic abnormalities (5, 11%), congenital heart disease (3, 7%) and gastrointestinal abnormalities (2, 4%). The medical management included the use of prophylactic antibiotics and intermittent bladder catheterisation. Surgical management included abdominoplasty with orchidopexy and circumcision. At the last clinic visit, severe reductions in renal function were noted in 11 (58%) of the patients under the age of 2 years, whereas normal renal function was present in 14 (56%) of the patients over 2 years of age. The default rate was 57%; 6 (14%) patients were transferred to an adult clinic and 2 (4%) patients died. Conclusions: The patient profiles and the management recorded are comparable with other reported series. There are differences in the frequencies of congenital malformations and the rates of surgical intervention. The renal outcome for children older than two years was favourable compared to younger children. Progression to end-stage renal disease was observed infrequently, but this may be underestimated in view of the high default rate.

Prevalence of diverse complications and its association with karyotypes in Japanese adult women with Turner syndrome-a questionnaire survey by the Foundation for Growth Science.

The reported prevalence of complications in Turner Syndrome (TS) was highly variable because of the rarity and the limited numbers analyzed. Again, possible presence of other complications that are not described as specific for TS, is also speculated. To resolve these issues, a questionnaire survey was conducted in hGH treated 492 patients with adult TS (17-42 years). The possible association with these complications and karyotypes were also analyzed. The complications and their prevalence were as follows: chronic thyroiditis (25.2%), inflammatory bowel disease (1.8%), congenital cardiovascular anomaly (11.8%), urinary tract malformation (11.8%), low bone mineral density (BMD) (42.9%), scoliosis (8.4%), hearing loss (6.2%), epilepsy (2.8%) and schizophrenia (0.9%). The majority of prevalence of these diseases in TS was higher than in the general population. In distribution, the most frequent karyotype was 45,X monosomy (28.9%), followed by 45,X/46,X,Xi (16.9%), 46,X,Xi (9.1%), and 45,X/46,XX (6.3%), while other mosaic 45,X was noted in 29.9%. Regarding the karyotype, cardiovascular anomaly was more frequent in the 45,X group and less in the 46,X,Xi group. Urinary tract malformation and epilepsy were frequently associated with the chromosome 45,X. The prevalence of low BMD was noticed more in the chromosome 46,X,Xi and 45,X/46,X,Xi, and less in other mosaic 45,X. In conclusion, the more exact prevalence of diverse complications was clarified and it exceeded the prevalence of the majority of complications in general population. As novel findings, it was observed that the prevalence of epilepsy was significantly high, and epilepsy and low BMD were frequently associated with the specific karyotypes.

Infants with prenatally diagnosed kidney anomalies have an increased risk of urinary tract infections.

This study estimated the urinary tract infection (UTI) risk in a nationwide cohort of infants prenatally diagnosed with parenchymal kidney anomalies compared with a comparison cohort. A Danish population-based nationwide cohort of foetuses diagnosed with parenchymal kidney anomalies between 2007 and 2012 had previously been identified. These were compared with foetuses without kidney anomalies who were prenatally scanned the same year. Live born infants were followed from birth until the diagnosis of UTI, emigration, death or two years of age. Cumulative incidences of UTIs were computed. Mortality was estimated using the Kaplan-Meier method. We identified 412 foetuses with parenchymal kidney anomalies out of 362 069 who underwent ultrasound scans and 277 were born alive. The overall risk of a UTI before the age of two years was 19%, and it was 14% among infants without prenatally diagnosed co-occurring urinary tract malformations. The corresponding risk in the 4074 controls was 1%. After two years, mortality was 2.2% in infants with prenatally diagnosed parenchymal kidney anomalies and 0.2% in the controls. Infants prenatally diagnosed with parenchymal kidney anomalies had a substantially increased risk of UTI. Awareness of this increased risk may facilitate earlier diagnosis of UTIs in this population.

Erratum to: A best practice position statement on pregnancy in chronic kidney disease: the Italian Study Group on Kidney and Pregnancy.

Pregnancy is increasingly undertaken in patients with chronic kidney disease (CKD) and, conversely, CKD is increasingly diagnosed in pregnancy: up to 3 % of pregnancies are estimated to be complicated by CKD. The heterogeneity of CKD (accounting for stage, hypertension and proteinuria) and the rarity of several kidney diseases make risk assessment difficult and therapeutic strategies are often based upon scattered experiences and small series. In this setting, the aim of this position statement of the Kidney and Pregnancy Study Group of the Italian Society of Nephrology is to review the literature, and discuss the experience in the clinical management of CKD in pregnancy. CKD is associated with an increased risk for adverse pregnancy-related outcomes since its early stage, also in the absence of hypertension and proteinuria, thus supporting the need for a multidisciplinary follow-up in all CKD patients. CKD stage, hypertension and proteinuria are interrelated, but they are also independent risk factors for adverse pregnancy-related outcomes. Among the different kidney diseases, patients with glomerulonephritis and immunologic diseases are at higher risk of developing or increasing proteinuria and hypertension, a picture often difficult to differentiate from preeclampsia. The risk is higher in active immunologic diseases, and in those cases that are detected or flare up during pregnancy. Referral to tertiary care centres for multidisciplinary follow-up and tailored approaches are warranted. The risk of maternal death is, almost exclusively, reported in systemic lupus erythematosus and vasculitis, which share with diabetic nephropathy an increased risk for perinatal death of the babies. Conversely, patients with kidney malformation, autosomal-dominant polycystic kidney disease, stone disease, and previous upper urinary tract infections are at higher risk for urinary tract infections, in turn associated with prematurity. No risk for malformations other than those related to familiar urinary tract malformations is reported in CKD patients, with the possible exception of diabetic nephropathy. Risks of worsening of the renal function are differently reported, but are higher in advanced CKD. Strict follow-up is needed, also to identify the best balance between maternal and foetal risks. The need for further multicentre studies is underlined.

Sekundarni psevdohipoaldosteronizem pri novorojenčku z akutnim vnetjem sečil – Prikaz primera

Hiponatremia and hyperkalemia in a newborn can be a life threatening disorder caused by different diseases, including congenital adrenal hyperplasia, or less frequently by a genetical or acquired tubular cell resistance to aldosteron, called pseudohypoaldosteronism. Secondary pseudohypoaldosteronism is a rare, reversible electrolyte disorder caused by aldosterone resistance in infants with congenital urinary tract malformations and/or urinary tract infection.We present a 4-week-old boy with severe hyponatremia, hyperkalemia and elevated aldosterone levels during an episode of pyelonephritis. The disorder improved completely with antibiotic treatment, rehydration and electrolyte correction. Further investigations showed no structural urinary tract anomalies. According to the literature, we concluded that electrolyte disturbances were caused by aldosterone resistance of the inflamed tubular cells and subsequent defective transepithelial sodium transport.

Copy-number variation analysis in familial nonsyndromic congenital anomalies of the kidney and urinary tract: Evidence for the causative role of a transposable element-associated genomic rearrangement

Most congenital anomalies of the kidney and urinary tract (CAKUT) are sporadic, but familial occurrence has been described, suggesting a genetic contribution. Copy-number variations (CNVs) were detected in patients with CAKUT to identify possible novel genomic regions associated with CAKUT. CNVs were investigated in 7 children with CAKUT from three unrelated families using array comparative genomic hybridization: female monozygotic twins with bilateral duplex collecting system/vesicoureteral reflux (VUR)/unilateral renal hypodyspasia (URHD); two male siblings with VUR/URHD; 3 male second cousins, one with bilateral VUR/URHD, one with bilateral VUR and one with ureterovesical junction obstruction (UVJO). Five patients had a normal constitution of CNVs, one had a duplication of 0.2 Mb on the 5q-arm (5q23.3), probably unrelated to CAKUT, and one with UVJO had a 1.4 Mb deletion on the 17q-arm (17q12) which includes a known CAKUT gene, HNF1B. The phenotype of HNF1B deletion was extended including renal magnesium wasting. A higher coverage in transposable elements (TEs) was found in the deleted region compared with the expected density in any random genomic region. Notably, the 5′ breakpoint was mapped within a solo long terminal repeat (LTR) sequence. Moreover, highly similar members of solo LTR and mammalian interspersed repetitive (MIR) elements, as well as nucleotide sequence microhomology were detected at the breakpoint regions. In conclusion, the deletion detected in one patient suggests this genomic imbalance as causative for UVJO. A not very well known phenotype of HNF1B deletion resulting in both low urinary tract malformations and renal wasting of magnesium was described. The high load in TEs of the deleted region, the presence of highly similar elements, and the microhomology found at breakpoint regions may have contributed to the generation of the deletion. CNV analysis could reveal novel causative genomic regions in patients with CAKUT, and further studies in larger cohorts are needed.

Mutations in the leukemia inhibitory factor receptor (LIFR) gene and Lifr deficiency cause urinary tract malformations.

Congenital anomalies of the kidneys and urinary tract (CAKUT) are the most common cause of chronic kidney disease in children. As CAKUT is a genetically heterogeneous disorder and most cases are genetically unexplained, we aimed to identify new CAKUT causing genes. Using whole-exome sequencing and trio-based de novo analysis, we identified a novel heterozygous de novo frameshift variant in the leukemia inhibitory factor receptor (LIFR) gene causing instability of the mRNA in a patient presenting with bilateral CAKUT and requiring kidney transplantation at one year of age. LIFR encodes a transmembrane receptor utilized by IL-6 family cytokines, mainly by the leukemia inhibitory factor (LIF). Mutational analysis of 121 further patients with severe CAKUT yielded two rare heterozygous LIFR missense variants predicted to be pathogenic in three unrelated patients. LIFR mutants showed decreased half-life and cell membrane localization resulting in reduced LIF-stimulated STAT3 phosphorylation. LIFR showed high expression in human fetal kidney and the human ureter, and was also expressed in the developing murine urogenital system. Lifr knockout mice displayed urinary tract malformations including hydronephrosis, hydroureter, ureter ectopia, and, consistently, reduced ureteral lumen and muscular hypertrophy, similar to the phenotypes observed in patients carrying LIFR variants. Additionally, a form of cryptorchidism was detected in all Lifr-/- mice and the patient carrying the LIFR frameshift mutation. Altogether, we demonstrate heterozygous novel or rare LIFR mutations in 3.3% of CAKUT patients, and provide evidence that Lifr deficiency and deactivating LIFR mutations cause highly similar anomalies of the urogenital tract in mice and humans.

The Role of Early Diagnosis of Hepatorenal Cystic (HRC) Syndrome in Children-Clinical Trial.

ABSTRACT: The hepatorenal cystic (HRC) syndrome is a heterogeneous group of severe monogenic conditions that may be detected before birth. Effective programme evaluation of children with HRC syndrome is a systematic way to identify the renal and urinary tract malformations which represent the most common cause of end-stage renal disease (ESRD). We conducted a study involving 50 patients, who were between 3 months and 16 years of age, with multiple admissions in the Nephrology Department of “Maria Sklodowska Curie” Children Emergency Hospital from Bucharest, during 6 years (April 14th 2010-October 24th 2016), to evaluate the HRC syndrome. The admission symptomatology was mainly represented by the nephrology evaluation which was essential in the management of children’s polycystic kidney disease. For example, a premature infant (gestational age=32 weeks) with positive heredo-collateral history (mother and grandmother were diagnosed with polycystic kidney disease), was tested positive for cystic renal disease after the fetal morphology was performed. It was also done a genetic determination for the presence of PKD1 and PKD2 mutations which are specific to autosomal dominant polycystic kidney disease-ADPKD. However, the genetic test was negative and a postnatal nephrological evaluation was performed using renal ultrasound. The image revealed autosomal recessive polycystic kidney disease-ARPKD. This study emphasizes the importance of an early diagnosis (prenatal, neontal, postnatal) correlated with the admission symptoms and also with the genetic diagnosis (mutations of PKD1 and PKD2).

The Fatal Outcome of a Child with a Delayed Posterior Urethral Valve Diagnosis in a Low Income Country: A Case Report and Take Home Messages

Introduction: When faced with early urinary tract infections in infants, there is a need to do diagnostic imaging to exclude urinary tract malformations. Delayed diagnosis of this condition could lead to serious complications. Case presentation: We received a 2 months old male infant referred for better management of an acute kidney injury (AKI) with septicemia. He had a past medical history of febrile urinary tract infection. Our diagnosis was that of acute kidney injury and septicemia associated to a posterior urethral valve. The initial treatment included broad spectrum antibiotics, management of AKI complications and vesicostomy to relief the urinary obstruction prior to valve ablation. We unfortunately lost the infant on day 3 following surgery from severe refractory hyperkalemia and a uremic syndrome. Conclusion: This case is a call to clinicians' attention in low income countries to always check for urinary tract malformations when confronted with an infant presenting a febrile urinary tract infection.