Qian Shen

Efficacy of rituximab therapy in children with refractory nephrotic syndrome: a prospective observational study in Shanghai

BackgroundIdiopathic nephrotic syndrome is the most common glomerular disease in children. This study was undertaken to observe the efficacy and side-effects of rituximab (RTX) in treating children with different types of refractory primary nephrotic syndrome.MethodsTwelve patients with steroid dependent nephrotic syndrome (SDNS), frequently relapsing nephritic syndrome (FRNS), and steroid resistant nephrotic syndrome (SRNS) were enrolled in our study. There were obvious drug side-effects, and proteinuria remained difficult to control. RTX was administered at a dose of 375 mg/m2 body surface area, once or twice weekly.ResultsThe male to female ratio was 3:1, and the onset age was 1.6–8.9 years. There were 9 patients with steroid sensitive nephrotic syndrome (SDNS or FRNS), and 3 patients with SRNS. There were 7 patients with minimal change disease (MCD), 3 patients with focal segmental glomerular sclerosis (FSGS), 1 with focal proliferative glomerulonephritis, and 1 without renal biopsy. The total effective treatment rate of RTX was 91.67%, and for 77.78% of the patients, steroid dosage could be reduced. Six months before and after RTX infusion, the mean steroid dosage was significantly decreased (P=0.014) and the recurrence number was significantly reduced (P<0.001). The results were better in MCD patients than in FSGS patients (P=0.045). There was no significant difference between FRNS/SDNS and SRNS patients (P=0.175). During RTX administration, 3 patients developed skin rashes, 1 developed hypotension, and 1 developed a fever. One patient experienced a persistent decrease in serum immunoglobulin level but without serious infection.ConclusionRTX was effective in the treatment of refractory nephrotic syndrome, and it could significantly reduce the use of steroid and immunosuppressants.

Renal histological features of school-age children with asymptomatic haematuria and/or proteinuria: a multicenter study.

The risk of asymptomatic haematuria and/or proteinuria development into chronic progressive glomerulonephritis (CPG) is unclear. The indications for renal biopsy and follow‐up on these asymptomatic children remain controversial.

Mutational analysis of AGXT in two Chinese families with primary hyperoxaluria type 1

BackgroundPrimary hyperoxaluria type 1 is a rare autosomal recessive disease of glyoxylate metabolism caused by a defect in the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT) that leads to hyperoxaluria, recurrent urolithiasis, and nephrocalcinosis.MethodsTwo unrelated patients with recurrent urolithiasis, along with members of their families, exhibited mutations in the AGXT gene by PCR direct sequencing.ResultsTwo heterozygous mutations that predict truncated proteins, p.S81X and p.S275delinsRAfs, were identified in one patient. The p.S81X mutation is novel. Two heterozygous missense mutations, p.M1T and p.I202N, were detected in another patient but were not identified in her sibling. These four mutations were confirmed to be of paternal and maternal origin.ConclusionsThese are the first cases of primary hyperoxaluria type 1 to be diagnosed by clinical manifestations and AGXT gene mutations in mainland China. The novel p.S81X and p.I202N mutations detected in our study extend the spectrum of known AGXT gene mutations.

Assessment of chronic renal injury from melamine-associated pediatric urolithiasis: an eighteen-month prospective cohort study.

BACKGROUND The illegal use of melamine in powdered baby formula resulted in a widespread outbreak of melamine-associated pediatric urolithiasis and kidney damage in China in 2008. We conducted this study because more needs to be known about the long-term effects of melamine-associated urolithiasis and kidney damage. OBJECTIVES To determine the prognosis and long-term implications of chronic kidney damage in children with urolithiasis resulting from melamine consumption. DESIGN Prospective cohort study. SETTING Children’s Hospital of Fudan University. PATIENTS AND METHODS Children six years of age or older with a history of having consumed melamine-contaminated milk powder were voluntarily screened. We measured urinary microprotein profiles [microalbumin (ALBU), immunoglobulin G (IgG), and N-acetyl-β-D-glucosidase (NAG)] and creatinine (CR) results at 6 and 18 months in children with melamine-associated urolithiasis. This study was conducted from September 17 to October 15, 2008. MAIN OUTCOME MEASURES Changes in urinary microprotein profiles. RESULTS Of 8335 children screened, 102 children (1.22%) were diagnosed with melamine-associated urolithiasis. Follow-up rates at 6 and 18 months were 91.4% (96/105) and 89.2% (91/102), respectively. Eighteen months later, 90.3% patients had spontaneously passed a stone. The incidence rates of proteinuria and microscopic hematuria at 6 months were significantly higher than at 18 months (P=.029 and P=.017, respectively). The proportion of patients with abnormal ALBU/CR, IgG/CR and NAG/CR at 6 months (27.6%, 17.1% and 21.1%, respectively) was significantly higher than at 18 months (6.4%, 5.1% and 12.8%, respectively). The high concentration of melamine consumed was the primary factor correlated with the high microprotein levels. Approximately 90% melamine-associated urolithiasis cases can be resolved within 18 months by non-surgical therapy. CONCLUSION The long-term presence of stones associated with a previous exposure to melanine can cause chronic kidney glomerular and tubular injuries. Passing these stones as soon as possible can reduce kidney injury and accelerate recovery. LIMITATIONS We could not control for possible selection bias due to more visits to our hospital or visits to our hospital after diagnosis at other hospitals, which might have increased the rate of diagnosis.

A de novo and novel mutation in the EYA1 gene in a Chinese child with branchio-oto-renal syndrome

Branchio-oto-renal (BOR) syndrome is a rare autosomal dominant disorder characterized by branchial cleft fistulae or cysts, preauricular pits, ear malformations, hearing loss, and renal anomalies. Mutations in the human homologue of the Drosophila eyes absent gene (EYA1) are the most common cause of BOR syndrome. PCR and direct sequencing were used to investigate all of the exons and exon-intron boundaries in the EYA1 gene in a patient with BOR syndrome from China. The patient was a child who displayed clinical features of BOR syndrome. Analysis of mutations in the EYA1 gene revealed a novel single base-pair deletion resulting in a truncated protein (c.1381delA; p.R461fs467X), and an analysis of mutations in the family revealed that this mutation was a de novo mutation. This is the first case of BOR syndrome in mainland China to be diagnosed based on clinical manifestations and mutations in the EYA1 gene. The novel c.1381delA mutation detected here expands the spectrum of known mutations in the EYA1 gene.

Early detection of congenital anomalies of the kidney and urinary tract: cross-sectional results of a community-based screening and referral study in China

Objective To establish an effective screening model of congenital anomalies of the kidney and urinary tract (CAKUT) using ultrasound among neonates in Shanghai, China. Design Cross-sectional study. Setting A three-level screening model for CAKUT in neonates based on the child healthcare system was established since 2010 in Minhang District, Shanghai, China. Participants During 2010–2015, neonates with criteria such as preterm, low birth weight and so on were eligible to participate in the study. Cases with renal pelvis dilatation (RPD) and other abnormal renal findings were managed based on presumed strategies. Main outcome measures The proportion of RPD and other renal and urinary tract anomalies; number of diagnosed CAKUT under integrated management, especially obstructive uropathy. The anterior–posterior renal pelvic diameter (APRPD) cut-off points for likelihood of obstructive uropathy and need for surgery. Results A total of 8827 infants were consecutively screened. Absolute and relative rates of different degrees of RPD classified by APRPD were: mild (5–9.9 mm), 984 (11.1%); moderate (10–14.9 mm), 176 (2.0%); severe (≥15 mm), 20 (0.2%). Of 639 followed cases with RPD, 11 were diagnosed as obstructive uropathies. Of these, nine patients underwent surgery, at median age 2 months. A total 85.4% of mild, 62.5% of moderate and 30.0% of severe RPD cases resolved spontaneously. Other renal and urinary morphological abnormalities were diagnosed in 15 (0.2%) patients. The APRPD cut-off points for significant obstructive uropathy and need for surgery were 9.7 mm and 13.5 mm, respectively. Conclusions This three-level screening model is an effective and feasible strategy for early detection and intervention of CAKUT in the early postnatal period, especially for patients with high-grade RPD and other renal and urinary malformations. This strategy could be useful in China and other developing areas with limited medical resources.