Clinical Analysis Of Congenital Anomalies Of Kidney And Urinary Tract (CAKUT) And Correlation Study Between CAKUT And GEN1

PART IObjective:A retrospective study was done on the diagnosis and treatment of CAKUT in a single center of Children’s Hospital of Fudan University from Jan.2005to Dec.2010, to provide clues to the early diagnosis of CAKUT.Methods:Collect the medical records of the cases with discharge diagnosis as CKAUT and analysis the data of categorical composition, clinical manifestations, diagnosis and treatment from the cases with the intraoperative diagnosis or the imaging diagnosis.Results:A total of1358out of102442patients (1.33%) were documented as CAKUT during the survey period. There are913cases of male and445cases of female. The male to female ratio is2.05:1; Average age of first admission is (3.0±3.4) years old.1. The diagnosis CAKUT hospitalization constitute over2005-2010showed a slow trend of increasing(P<0.05). The CAKUT data of hospitalized children because of melamine stone screening in the second half of2008and the first half of2009rose0.72and0.16percent respectively as compared with normal clinic data.2. The major CAKUT types were PUJO(567cases,41.8%), VUR(217cases,16.0%), duplex collecting system(154cases,11.3%), UVJO(143cases,10.5%); the trend of these4CAKUT types (exclude the screening data) was not significant; the composition of PUJO(2008and2009) and UVJO (2008) diagnosed in the melamine stone screening were significantly higher than the composition of the corresponding normal clinic; the age of PUJO and UVJO was less than the age of normal clinic in the same period.3. In the1358patients, patients with non-symptom was about44%(592/1358). The majorities were found by antenatal B ultrasound (406cases,29/9%), renal stone screening (112cases,8.2%) and health examination (74cases,5.4%). The proportion of patients with symptoms was about56%(766/1358). The majorities were UTI with fever (279cases,19.9%), abdominal symptoms (217cases,16.0%) and voiding dysfunction (79cases,5.8%).4. The cases in PUJO, UVJO, duplex collecting system, dysplastic kidney, PKD and ureterocele were mainly discovered by abnormal prenatal B ultrasound images.77.3%of the cases in VUR had febrile urinary tract infections.5.1330(98.0%) CAKUT patients had B ultrasound examination and1262cases were found abnormal images. The detection rate of abnormal B ultrasound in VUR was68.5%(137/200), and the detection rate of abnormal B ultrasound in the rest CAKUT types were all above94.0%.400/1358cases(29.4%) had MCU examination to identify the VUR.573cases,516cases and209cases were performed MR, IVP and IVP examination respectively to learn the form of the urinary system.1061cases and308cases were performed DTPA and DMSA examination to learn the function of urinary system.6. The mean age of patients identified on antenatal ultrasound was the lowest in PUJO and UVJO patients, followed by those diagnosed by renal stone screening and clinical manifestations (P<0.05between either2groups in antenatal ultrasound screening, renal stone screening, and manifestations). The mean affected split renal function measured in PUJO patients identified on antenatal ultrasound, renal stone screening, and clinical manifestations were36.3%,41.0%, and33.3%, respectively (P<0.05between either2groups in antenatal ultrasound screening, renal stone screening, and manifestations). The mean pelvic dilatation in PUJO patients identified by clinical manifestations was more severe than that in patients diagnosed on antenatal ultrasound and renal stone screening.Conclusions:We were the first one to report the detail types and clinical features of CAKUT, and all the cases in this paper had exact etiological diagnosis and history details. So this paper enriched the acknowledge of CAKUT and the status of CAKUT patients. The majority of CAKUT cases in our center were PUJO, followed by VUR, DCS, and UVJO. CAKUT patients were mainly found by antenatal B ultrasound, and the follow-up survey was very helpful in the early intervention of CAKUT disease. Even if there was an antenatal B ultrasound examination in China, there were still some cases undiscovered. And the symptoms of CAKUT were hard to be noticed, so we proposed the combined prenatal and postnatal ultrasound screening. This mode could find these patients effectively and hold back the process of CAKUT when their renal function were not uncompensated. So it was needed for early CAKUT detection. Studies that are more rigorous are warranted to validate these findings and provide clues for early CAKUT detection strategies in China.PART IIAlthough some CAKUT disease phenotype was part of a syndrome or the patients hadObjective:This study the Han CAKUT patients GEN1gene exon nucleotide sequence analysis, to explore its possible relationship with the pathogenesis of CAKUT.Methods:According to the CAKUT phenotypes of the GEN1mutant mice, select a clear diagnosis of the follow diseases:duplex collecting system (36cases), unilateral renal agenesis (8cases), vesicoureteral reflux (VUR;43cases), pelviureteric junction obstruction (PUJO;33cases), ureterovesical junction (UVJO;14cases) and renal dysplasia (18cases) as case group.96cases of normal B-urinary system Han children were chosen as a control group. Collect subjects peripheral blood2ml in EDTA anticoagulant tube, extract genomic DNA, PCR amplify the coding exons of GEN1gene, sequence and analyze the results. If we found new mutations in GEN1exons, we would repeat sequencing with bi-directional to confirm the results. Then we collected the samples and medical histories of their parents for further study.Results:There were5patients presented with the GEN1missense mutations in case group. They were:314C>G (T105R; one PUJO and one VUR),1201C>T (R401TER; one UVJO),1609T>C (C537R; one VUR) and1730T>C (T577I; one PUJO), one synonymous mutations786C>T (S262S; one UVJO). These variations are heterozygous, and mutation detection rate was3.9%(5/152). We had not detected these variation in the control group. We collected the samples and medical histories of the parents of3patients, and found that the mutations were inherited from one of their patients, but their parents had no signs of CAKUT disease. In addition,10Genl gene polymorphism in gene banks were confirmed in our study, but we have not found the allele frequencies and genotype frequencies were significantly different between the case group and control group.Conclusion:In this study, we had CAKUT patients GEN1mutation analysis of the coding exons for the first time, and found three missense mutations and one stop-gained mutation. How GEN1work in the CAKUT disease was still unknown, and the mutations found in our study need further research to find out the relationship between GEN1and CAKUT disease.