Congenital Anomalies of the Kidney and the Urinary Tract in Newborns from Lviv Region (West Ukraine) For 2006-2017

Congenital anomalies of the kidney and the urinary tract (CAKUTs) are relatively common birth defects. Aim of our study was to assess the frequency in newborns congenital anomalies of the kidney and the urinary tract from Lviv region (Ukraine) for 2006-2017 according to the medical reports by the maternity hospitals. Methods: 272 newborns from Lviv region (West Ukraine) who were diagnosed according to the reporting form by the maternity hospitals with congenital anomalies of the kidney and the urinary tract were analyzed over a period of 12 years. Results: During the study period (2006-2017), there were 342,894 births reported, and 8144 newborns were with congenital anomaly, an average incidence of 23.8 per 1000 births. There were 272 cases of CAKUT, an average incidence of 0.8 per 1000 births. The lowest frequency of CAKUT was observed 0.5 per 1000 newborns in 2008, 2013, 2015, 2017 years. The high frequency of this pathology 1.1 -1.2 per 1000 newborns was diagnosed in 2011-2012 years. The most common birth defects of the kidney and urinary tract in newborns in Lviv region were congenital hydronephrosis 137 (50.4%) and polycystic kidney 72 (26.5%). Less commonly in newborns diagnosed оther specified congenital malformations of kidney 14 (5.2%) and Potter sequence 13 (4.8%). Conclusion: The importance of this study resides, to the best of our knowledge, in the fact that the largest group of patients in Ukraine was analyzed and assessed. Our study of the occurrence of urinary malformations in Lviv region (West Ukraine) for the 2006 to 2017 period showed wave-like dependence.


Introduction
Congenital anomalies of the kidney and the urinary tract (CAKUTs) are relatively common birth defects [1][2][3]. Congenital anomalies of the kidney and urinary tract (CAKUT) represent a broad range of disorders that result from abnormalities of the urinary collecting system, abnormal embryonic migration of the kidneys, or abnormal renal parenchyma development [4]. The risk factors for these anomalies are not clearly identified and include many factors [5][6][7]. The pathogenesis of CAKUT is not well understood, because identifying the genetic architecture of CAKUT is difficult due to the phenotypic heterogeneity and multifactorial genetic penetrance [8,9].
Broad phenotypic spectrum of CAKUT and variability in genotype-phenotype correlation indicate that pathogenesis of CAKUT is a complex process that depends on interplay of many factors [10,11].
The condition may appear as an isolated feature or as part of a syndrome in association with extra-renal manifestations [12][13][14].
Aim of our study was to assess the frequency of congenital anomalies of the kidney and the urinary tract in newborns for 2006-2017 yy. According to the medical reports by the maternity hospitals from Lviv region (West Ukraine).

Materials and Methods
This retrospective study evaluated 272 newborns with congenital anomalies of the kidney and the urinary tract who were diagnosed over a period of 12 years (2006-2017) according to the reporting form submitted by the maternity hospitals from Lviv region (West Ukraine).
Inclusion criteria -newborns with congenital anomalies of the kidney and the urinary tract. Exclusion criteria -newborns with multiple birth defects or other syndromes except Potter sequence.
All patients were assessed with physical examination and underwent a set of diagnostic tests including general clinical tests, family history, complicated childbirth, abdominal ultrasonography (if needed) in maternity hospitals. Congenital anomalies in newborns were recorded by birth obstetrician in a birth defects form. In addition we analysed the following data for each patient: Sex and birthplace.
In 1995, the first gene defect described as being causative of CAKUT was a frameshift deletion in PAX2 in a family with optic nerve coloboma, renal hypoplasia and vesicoureteral reflux [21]. PAX2 plays a critical role in kidney development and its mutations (more than 55 have been reported so far) can lead to different isolated CAKUT phenotypes [22].
CAKUT cover a wide range of structural malformations that result from a defect in the morphogenesis of the kidney and/or the urinary tract [15,23,24].
Congenital anomalies of kidney and urinary tract (CAKUT) are observed in 3-6 per 1,000 live births and account for 40-50% of the etiology of chronic kidney disease (CKD) in children worldwide [2].
At the same time, Tain YL, et al. notes that birth defects of the kidney and urinary tract and glomerular disease are the most common diagnoses of kidney disease in childhood; the incidence of congenital anomalies of the kidney and urinary tract during the past decade has been estimated to be 0.4 to 4.0 cases per 1000 births [9]. In France of the 1678 infants with CAKUT born during 26 years in 346,831 consecutive births prevalence at birth was 4.8 per 1,000 [25].

Discussion
Hildebrandt F. notes that the frequency of CAKUT is 3-6 per 1,000 live births [2] but frequency of this pathology in Lviv region (West Ukraine) in 2011-2012 is 1.1-1.2 on 1000 newborns. This frequency in the Lviv region is lower than in other regions of Ukraine [5] and in France [25] but higher than in Taiwan [9]. The discrepancy in reported incidence is likely to be related to the ethnic differences, the method of diagnosis, size of the study population and the way in which the birth defect information used was recorded.
Congenital anomalies of the kidney and urinary tract continue to be a group of diseases with different degrees of severity and many of them require a multidisciplinary approach for accurate diagnosis and better treatment [1].
For doctors it is very important to establish the correct diagnosis in order to facilitate adequate genetic counseling and to alert the families of other possible affected members that could benefit from earlier intervention [1,15,29].
Since the spectrum of CAKUT is different and heterogeneous various studies predominate in variety birth defects [10,16,24]. In our study prevalence congenital hydronephrosis and polycystic kidney. Most often congenital hydronephrosis diagnosed among all the defects [4,10].
Several of these renal abnormalities are part of a syndrome or sequence (especially Potter sequence) that can be cords from maternity hospitals. Newborns out come from the maternity hospital three days after the birth child. So in the first days of the birth doctor can not confirm this pathology. Early diagnosis is inadequate as clinical manifestations of congenital anomalies of the kidney and the urinary tract and appear only in the case of adherence to infections, or by prenatal ultrasonography.
During the period (2006-2017) of study, there were 342 894 births reported, and 8144 newborns had congenital anomaly, an average incidence of 23.8 per 1000 births. There were 272 cases of CAKUT, an average incidence of 0.8 per 1000 births ( Table 1 The most common birth defects of the kidney and urinary tract ( Table 2) were congenital hydronephrosis -137 (50.4%) and polycystic kidney -72 (26.5%) in newborns from Lviv region (West Ukraine). Table 2 shows the trend of incidence of congenital anomalies and CAKUT over time. Very rarely was met renal dysplasia -1 (0.4%) and other congenital malformations of bladder and urethra -1 (0.4%). The same frequency had been established of renal hypoplasia and congenital single renal cyst -6 cases (2.2%). The spectrum of congenital anomalies of the kidney and urinary tract was extremely broad and range  4. Newborns out come from the maternity hospital three days after the birth child. So in the first days of the birth doctor can not confirm this pathology. Early diagnosis is inadequate as clinical manifestations of congenital anomalies of the kidney and the urinary tract and appear only in the case of adherence to infections, or by prenatal ultrasonography.
The importance of this study resides, to the best of our knowledge, in the fact that the largest group of patients in Ukraine was analyzed and assessed. Our study of the occurrence of urinary malformations in Lviv region (West Ukraine) for the 2006 to 2017 period showed wave-like dependence.
14. Vivante A, Kohl S, Hwang D, et al. (2014) Single-gene causes of congential anomalies of the kidney and urinary tract (CAKUT) in confirmed and sometimes treated by a multidisciplinary approach including fetal ultrasonography and vesico-amniotic shunt placement to relieve obstruction while in the fetal period, or by other imaging modalities, molecular analysis, and pathologic examination after birth [1,5,30].
Potter sequence refers to a group of features that can result when there is too little amniotic fluid (oligohydramnios) surrounding a baby while in the uterus. This can cause distinct facial features (Potter facies), which may include a flattened nose, recessed chin, skin folds covering the corners of the eyes (epicanthal folds), and low-set abnormal ears. Having low amniotic fluid can also result in underdevelopment of the lungs (pulmonary hypoplasia). Other associated features may include eye malformations and heart defects [1,3,17,25].
In first of all the Potter sequence was diagnosed on base of facial features typical of babies with this syndrome. In our cohort we diagnosed 13 (4.8%) newborns with Potter sequence -8 boys and 5 girls. Among these newborns 7 had bilateral renal agenesis and 6 -polycystic kidney diseases. Signs that might be identified on ultrasound include kidney abnormalities.
Although the most severely affected newborns progress within the first year of life, doctors have problems with early diagnosis of CAKUT. This review focuses on the genetic mechanisms (single-gene mutations, modifier genes) leading to renal system anomalies in patients and discusses emerging insights into the role of epigenetics, in utero environmental factors in the pathogenesis of CAKUT [3,5,10].
One of the possible problems underdiagnosis of CAKUT is clinically asymptomatic and doctors may be found only when are actively sought, or are diagnosed by prenatal ultrasonography in the latter period of pregnancy. The natural course of CAKUT is very heterogeneous [11,15,24,25]. Although the most severely affected newborns progress this pathology within the first few months of life, kidney function improves in most children born with CAKUT, typically reaching a peak around age 3-4 years.
The study is also important as it may help to raise the awareness of surgical pediatric intervention and to emphasize the loss of babies with congenital abnormalities.