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Objective:To investigate and analyze the clinical phenotypes and genotypes in children diagnosed with nephronophthisis (NPHP), and to provide references for clinical diagnosis.Methods:Clinical data of 9 children with NPHP diagnosed by genetic testing in the Department of Nephrology, Wuhan Children′s Hospital from April 2017 to January 2022 were retrospectively collected. The clinical characteristics and genetic test results were analyzed.Results:The median onset age was 11.2(3.4, 14.2) years old in 9 patients, including 5 females and 4 males. There were 8 cases of glomerular proteinuria, 8 cases of renal tubular proteinuria, and 7 cases of reduced urinary gravity in 9 patients. All the children had varying degrees of impaired renal function at the time of diagnosis. Seven cases entered chronic kidney disease (CKD) stage 5, 1 case entered CKD stage 3, and 1 case entered CKD stage 4 at the time of diagnosis. All the children had renal ultrasound abnormalities of varying degrees: size change (3/9), echo enhancement (8/9) and cysts (3/9). Extrarenal phenotypes were present in 3 children. Genetic test showed that 6 patients had mutation of NPHP1 gene, 1 patient had mutation of WDR19 gene, 1 patient had mutation of NPHP3 gene and 1 patient had mutation of NPHP5 gene. Conclusions:Deletion mutation of NPHP1 gene is the most common, while NPHP3, NPHP5 and extremely rare WDR19 mutations have also been found in NPHP patients. The clinical manifestations of NPHP are not typical, so it is necessary to find a specific diagnosis method in the early.
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Objective:To assess the efficacy of Rituximab (RTX) in treating children with refractory nephro-tic syndrome.Methods:A retrospective study was carried out.Twenty-two children diagnosed with refractory nephrotic syndrome in the Department of Nephrology of Wuhan Children′s Hospital, Tongji Medical College, Huazhong University of Science and Technology from November 2018 to November 2020 were included in the study.All patients were treated with RTX.Patients with CD 19+ B lymphocytes≥1% total lymphocytes in peripheral blood were supplemented with one dose of RTX (375 mg/m 2), and each patient received 3-4 doses of RTX on average.The patients were treated with Mycophenolate mofetil after early discontinuation of calcineurin inhibitors (CNI). The Kaplan-Meier method was used to analyze the proteinuria relapse-free rate and the incidence of frequently recurrent nephrotic syndrome or steroid-dependent nephrotic syndrome in children after RTX treatment.The relapse times before and after using RTX were analyzed by the Wilcoxon signed rank test.Besides, the body mass indexes (BMI) and height of children before and after RTX treatment were compared by the rank sum test. Results:Of 22 patients studied, 20 patients accomplished the therapeutic protocol.One-year and two-year proteinuria relapse-free survival rates were 85% and 40%, respectively.The recurrence rate was reduced under the discontinuation of CNI.Compared with those before RTX treatment, the BMI and height of all children were significantly improved at 1 year and 2 years after RTX treatment (all P<0.05). However, no significant improvement was observed between 1 or 2 years after RTX treatment (all P>0.05). Conclusions:The use of RTX can effectively reduce the recurrence rate of refractory nephrotic syndrome even when hormones and other immunosuppressants are discontinued.At the same time, RTX can significantly improve the BMI and height of children.RTX is safe and effective for treatment of refractory nephrotic syndrome.
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Objective To elucidate the mutations of NPHS1 gene in children with sporadic steroid-resistant nephrotic syndrome (SRNS) in Southern Chinese Han ethnic group.Methods Peripheral blood samples were collected for genetic analysis from 40 patients with sporadic SRNS and 50 healthy volunteers as control.Genomic DNA was isolated from peripheral blood leucocytes.Twenty-nine exons and exon-intron boundaries of the NPHS1 gene were amplified by polymerase chain reaction.Mutational analysis was performed by DNA sequencing directly.Results Seven variants,928G＞A(D310N),2677A＞G (T893A),2869G＞C (V957L),IVS8+30C＞T,IVS21+14G＞A,IVS25-23C＞T and *142T＞C,of NPHS1 gene were found in 6 of 40 children with sporadic SRNS,whereas they were not found in 50 healthy controls.2677A ＞G,IVS8 +30C ＞T,IVS21 +14G＞A,IVS25-23C ＞T and *142T＞C were novel.Moreover,thirteen already reported NPHS1 polymorphisms,294C＞T,349G＞A,IVS3+15C＞T,IVS3+61A＞G,803G＞A,IVS8+68A＞G,1339G ＞A,1802G ＞C,2223C ＞T,2289C ＞T,IVS24 +36C ＞T,3315G＞A and IVS27 +45C ＞T,were detected in some patients and controls. Conclusions NPHS1 mutations in 6 of 40 children with sporadic SRNS in Southern Chinese Han ethnic group (15％) are detected.NPHS1 mutations are existed in Southern Chinese children,so it is necessary to perform the mutation analysis of NPHS1 gene in those children patients.