Study On Clinical Features And Causal Genes Of Congenital Unilateral Renal Agenesis

ObjectiveTo analyze the clinical features and screen the causal genes in adult patients with congenital unilateral renal agenesis(URA).MethodsWe enrolled URA patients at Department of Nephrology from January 2008 to January 2016.Demographic and baseline clinical data were recorded and analyzed.81 unrelated URA patients were screened of 25 genes previously reported URA-causing or related using targeted sequencing.Results1)In this study,118 URA patients were recruited,and 66.9% of patients were diagnosed accidentally by physical examination.At their initial clinic visit in our hospital,62 patients had developed renal injury symptoms(i.e.hypertension,proteinuria and renal insufficiency).Logistic regression analysis revealed that proteinuria [OR=5.89,95%CI(1.20,28.94)],hyperuricemia [OR=8.14,95%CI(2.11,31.36)] and kidney length < 120 mm [OR=10.51,95%CI(2.28,48.39)] were associated with renal insufficiency.2)Through screening pathogenic genes among 81 URA patients,we identified 42 different pathogenic mutations of 14 candidate genes in 36 patients,and the total number of mutations was 45.In the Fraser gene spectrum(including FRAS1,FREM2 and FREM1 genes),20 different mutations were identified and 20 patients had a total number of mutations 21.Clinical characteristics were compared between the group of mutation carriers in the Fraser gene spectrum and non-carriers.It showed that the left renal agenesis occurred more in mutation carriers than non-carriers(75% vs.43%,p=0.012),but other clinical parameters between the two groups showed no significant difference.ConclusionCongenital URA patients are not uncommon in clinical practice.Proteinuria,hypertension and renal insufficiency are common symptoms.Those with proteinuria,hyperuricemia or kidney length less than 120 mm perhaps have a much higher risk of renal insufficiency.FRAS1,FREM1 and FREM2 may be the main causal genes in Chinese URA patients.In mice,Fras1,Frem1 and Frem2 formed a ternary complex reciprocal stabilization at basement membrane,which is the upstream signal of GDNF during renal development.Our results indicate that missense mutations in the Fraser spectrum genes cause isolated URA.Patients carry mutations in the Fraser gene spectrum perform more frequently with left renal agenesis,but they do not show differences in clinical manifestations.