The Analysis Of The Relationship Between The Early Prognosis And Clinical Factors In VUR Patients And The Exploration Of The Pathogenesis

BackgroundPrimary vesicoureteral reflux (VUR) is a most common congenital urinary tract malformation disease of children.Reflux nephropathy can cause renal scarring, renal atrophy and renal function damage. In1996, collaborative group of pediatric renal transplantation in North America reported5.6%of the pediatric renal transplantation patients, the primary disease is VUR. In children,20%of hypertension patients can be caused by reflux nephropathy secondary to the VUR.Studies have shown that early detection of VUR and aggressive treatment can effectively reduce the incidence of reflux nephropathy, suggesting that the early diagnosis and treatment of VUR is important. Scholars of various countries have done a lot of research about pathogenesis, diagnosis, treatment and other aspects of VUR and found that with the increase of the age,a considerable portion of VUR patients can achieve reflux grade spontaneous resolution even complete resolution. So it is important to explore which clinical factor may influence the prognosis of the VUR patients, currently there is no relevant research about the Chinese VUR patients.Foreign scholars have done a large number of genomics research about the VUR pathogenesis,but at present there is no consistent conclusions. In recent years, some scholars assumed that the VUR was the outcome of urinary tract developmental delay. Put forward the hypothesis inferred from another aspect, currently there has been animal model to support this hypothesis.The first part of this study were retrospectively analyzed the VUR patients clinical data from January2000to December2009in our hospital to explore association between the early prognosis and clinical factors, hoping to deepen the understanding of the disease characteristics so as to establish diagnosis and treatment guideline in line with China’s national conditions.The second part of this study was focused on the expression of Pax2protein which should be trace expression in ureteral epithelium after birth in VUR.We further explore the epithelial cells apoptosis status and UPIII protein expression in the VUR patients ureter in order to explore the possible pathogenesis of the primary vesicoureteral reflux. Part I The analysis of the relationship between the early prognosis and clinical factors in VUR patientsObjective Primary vesicoureteral reflux (VUR) is a most common congenital urinary tract malformation disease of children.Reflux nephropathy can cause renal scarring, renal atrophy and renal function damage. Previous study show that:with the increase of the age, a considerable portion of VUR patients can achieve reflux grade spontaneous resolution, this part is to explore the relationship between the early prognosis and clinical factors in VUR patients.Method Retrospectively analyzed the VUR patients clinical data from January2000to December2009in our hospital,73VUR patients repeated MCU with1-2years followed up were included in the study, all of the patients only received maintenance dose of antibiotics to prevent infection, none of them were received surgery therapy. Reflux grade was based on MCU result, detection of renal damage was based static radionuclide renal scan (DMSA) results. Clinical data including gender, age, unilateral or bilateral reflux, reflux grade at initial diagnosis, the results of the first DMSA, repeated MCU result and urine culture during the follow-up. We established a database using statistical software SPSS19.0and analyzed:T test, Chi-square test and rank sum test on the balance of factors in each group; application Logistic regression to analysis the clinical factors which could influence the prognosis of VUR patients; Wilcoxon rank sum test to compare the differences between the2groups, Kruskal-Wallis rank sum test to compare differences among groups.Result (1) the general condition of73patients:①The mean age of73patients was2.23±2.22years (0.2-9.0years old) of which <2years old accounted for65.8%, MCU repeated at an average follow-up time was1.29±0.393years (1-2years), no patients underwent surgery during follow-up,all the patients only accepted maintenance dose of antibiotics to prevent infection.②27(37.0%) patients had renal damage,46of73(63.0%) patients had normal kidney based on the DMSA result,2patients with abnormal DMSA results have the eGFR value <90ml/min, both of them were CKD II patients, The remaining71patients all have the eGFR value>90ml/min.③Patients with renal damage of high grade reflux is5(25.0%),in moderate grade is16(41.0%) while in low grade reflux is6(42.9%), renal damage is no significant difference (P=0.425) in these groups.(2) The early follow-up results of the patients:all patients repeated MCU and DMSA examination during1-2years follow-up,41(56.16%) patients have achieved resolution, among these41patients,27patients (36.9%) have achived complete resolution;19(26.03%) patients have not achieved significantly resolution, worened reflux grade occurred in13(17.81%) patients.(3) Logistic regression analysis showed:①identify the clinical factors which could refluence the reflux resolution of VUR patients including: initial reflux grade OR=2.462(95%CI:1.015-5.973), renal damage OR=0.100(95%CI:0.029-0.347).②identify the clinical factors which could refluence the reflux complete resolution of VUR patients includeing renal damage OR=0.192(95%CI:0.056-0.654)③identify the clinical factors revelent to the reflux worening including: initial reflux grade OR=0.077(95%CI:0.013-0.457), renal damage OR=40.70(95%CI:4.032-410.824).(4) Two independent samples of the resolution rate in different reflux grade patients (mild, moderate and severe) with and without renal damage were compared by Wilcoxon rank sum test results and show that:significantly difference resolution rates (P<0.001) were noticed between with and without renal damage of moderate reflux patients in early reflux resolution (P<0.001).(5) Kruskal-Wallis rank sum test were used to analyze the resolution rate between group (mild, moderate, high) with and without renal damage,it showed that:no significant difference in resolution rate (P=0.978) between patients who have no renal damage regardless of reflux grade(mild, moderate, high), patients with renal damage with defferent reflux grade(mild, moderate, high) have a significantly difference (P=0.018) in grade resolution.Discussion (1) Renal damage is an important clinical factor for reflux grade resolution in VUR patients,it is also an important risk factor leading to reflux grade worsening.(2)High-grade reflux patients are more likely to achieve grade resolution than low reflux grade patients. But there was no difference in resolution rate between patients who had no renal damage with different reflux grade.(3)Mild and moderate grade reflux patients who without renal damage can achieve high rate resolution, but if in the event of kidney damage happened,these patients will have a high risk for reflux grade worsening. Therefore, the prognosis of low and moderate grade reflux patients is largely depended on whether these patients have renal damage, it is necessary to perform a close followed-up for these patients, surgery can be considered when necessary.(4) High grade reflux patients with no renal damage may be considered follow-up for1-2years.Then according to the latest MCU result to decide whether to perform surgery therapy.But high grade reflux patients with renal damage are still be the indications for surgery therapy.(5) There are few high grade patients who have renal damage in patients included in this study, the results may have some bias,we look forward greater sample size of VUR patients with renal damage in long-term follow-up.Part II The exploration the Pax2protein and the Pathogenesis of the primary vesicoureteral refluxObjective Observation of Pax2protein expressing in the patients ureteral tissues of primary vesicoureteral reflux to explore the relationship between rexpression of Pax2protein and the possible pathogenesis of primary vesicoureteral reflux.Method Parafin sections of26abnormal ureters (VUR) and3normal ureters were done with immunohistochemistry method and TUNEL to identify the expression of Pax2and epithelial cell apoptosis. Images were analyzed with microscope Motic image software.Result①Normal ureters have not showed significant Pax2protein expressing while abnormal ureters showed mass Pax2protein expressing;②Normal ureters have not showed siginificant epithelial cell apoptosis while abnormal ureters showed mass epithelial cell apoptosis.③There were significant diference in area between normal and abnormal groups (P<0.001).Discussion①The repressiong of pax2protein may be due to the apoptosis in the VUR patient ureter epithelial cell②Those epithelial cell under apoptosis status may not express UPIII protein normally.