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Objective: To investigate the clinical characteristics and related factors of corticosteroid induced adrenal crisis (AC) in children with primary nephrotic syndrome (NS). Methods: Case control study. The case group included 7 children aged 1 to 18 years with NS combined with AC hospitalized in Peking University First Hospital from January 2016 to May 2021 (AC group). According to the ratio of case group: control group 1: 4, 28 children aged 1 to 18 years who were diagnosed with NS without AC during the same period were matched as controls (non-AC group). Clinical data were collected. The clinical characteristics of AC were described. The clinical parameters were compared between the 2 groups by t test, Mann-Whitney U test or Fisher's test. Receiver operating characteristic (ROC) curve was used to analyze the cutoff values of clinical parameters for prediction of AC. Results: The AC group included 4 boys and 3 girls aged 6.9 (4.6, 10.8) years. The non-AC group included 20 boys and 8 girls aged 5.2 (3.3, 8.4) years. All AC events occurred during the relapse of NS with infection. Seven children had gastrointestinal symptoms such as nausea, vomiting and abdominal pain. Six children had poor mental state or impaired consciousness. No significant differences in NS course, corticosteroid treatment course, corticosteroid type, steroid dosage, steroid medication interval, the proportion of gastroenteritis and fever existed between the two groups (all P >0.05). Compared with the non-AC group, the duration from the onset of the relapse of NS until hospitalization in the AC group was significantly shorter (0.2 (0.1, 0.6) vs. 1.0 (0.4, 5.0) month, U =25.50 , P =0.005). The 24 h urinary total protein (UTP) level was significantly higher in the AC group (193 (135, 429) vs. 81 (17, 200) mg/kg, U =27.00 ,P =0.036) than the non-AC group. The serum albumin level in the AC group was significantly lower((13.1±2.1) vs. (24.5±8.7) g/L, t= -6.22, P <0.001) than the non-AC group. There were significantly higher total white blood cell counts ((26±9)×10 9 vs. (11±5)×10 9 /L, t= 4.26, P =0.004), percentage of neutrophils (0.71±0.08 vs. 0.60±0.19, t= 2.56, P =0.017) and the proportion of children with C reactive protein level≥8 mg/L (3/7 vs. 0, P =0.005) in the AC group than in the non-AC group. ROC curve analysis showed that the cutoff value of 24 h UTP was 122 mg/(kg·d) with a sensitivity of 100.0% and specificity of 70.4%. The cutoff value of serum albumin was 17.0 g/L with a sensitivity of 100.0% and specificity of 82.1%. Conclusions: Gastrointestinal symptoms and poor mental state were prominent manifestations of AC in children with NS. High 24 h UTP level, low serum albumin level, high peripheral white blood cell counts, high neutrophils percentage, and high C-reactive protein level during the early stage of NS relapse may be related to the occurrence of AC in children with NS.

Background: Thromboembolism is a life-threatening, limb-threatening or organ-threatening complication that occurs in patients with primary nephrotic syndrome (NS). There are few studies on the spectrum, complications and outcomes of thrombosis in children with NS. This study aimed to determine the spectrum of thrombosis and its relationship with the nephrotic state, treatment and outcomes in children and adolescents with primary NS., Methods: The medical records of subjects aged 1-18 years with NS complicated with thromboembolism treated at our centre within the last 26 years were retrieved. Data on the status of NS, site, symptoms and signs, laboratory investigations, diagnosis, treatment, complications and outcomes of thrombosis were collected and reviewed retrospectively. A severe complication was defined as a condition associated with thrombosis requiring a special diagnostic modality to confirm or a specific treatment such as surgical intervention. The outcome of thrombosis was defined as the status of thrombosis, as determined by imaging methods and the functional status with respect to the anatomic sites of thrombosis at the last follow-up. The permanent dysfunction of an organ or limb related to thrombosis was defined as a sequela., Results: We observed thrombosis in 1.4% (27/1995) of subjects with NS during the study period. There were 27 subjects with thrombosis, including 21 males and 6 females. Thrombosis was observed in 51.9% (14/27) of the study participants with steroid resistant NS. Most episodes of thrombosis occurred during the active stage of NS; however, 7.4% of thrombosis cases occurred during the remission of proteinuria. Renal vein thrombosis (33.3%) and pulmonary embolism (25.9%) were the most common types of thrombosis. Among the 17 subjects biopsied, minimal change disease and membranous nephropathy were the two most common findings. Six (22.2%) subjects experienced severe complications or sequelae; 1 had persistent intracranial hypertension, 1 had intestinal perforation, 1 had hypoxemia and pulmonary hypertension, 1 had lameness, 1 had epilepsy, and 1 had an askew mouth due to facial paralysis. In 19 (70.4%) subjects, the symptoms resolved completely or improved without severe complications or sequelae., Conclusions: Thrombosis mostly occurred in males of school age during the active stage of NS. Renal vein thrombosis and pulmonary embolism were the most common types of thrombosis. In most patients with thrombosis, the symptoms improved completely without complications with standard anticoagulation therapy. However, 22.2% had severe complications or sequelae requiring an advanced diagnostic modality and aggressive treatment.

Objective: To investigate the clinical features and side effects, with regard to glucocorticoid-induced ocular hypertension, glaucoma or cataract in children with primary nephrotic syndrome., Methods: Clinical data were collected and analyzed from 71 cases of primary nephrotic syndrome with glucocorticoid-induced ocular hypertension, glaucoma or cataract from Jun. 2014 to Jun. 2016. These children were hospitalized in Peking University First Hospital., Results: Totally 1 580 children with primary nephrotic syndrome were collected, glucocorticoid-induced complications in eyes were found in 71 cases, and the incidence was 4.5%. There were 66 cases with ocular hypertension, 2 cases with glucocorticoid glaucoma, 2 cases with glucocorticoid glaucoma combined with cataract, 1 case with high intraocular pressure combined with cataract. There were 41 boys and 30 girls with eye-related side effects caused by glucocorticoid. The average age of onset of glucocorticoid-induced eye adverse reactions in children with primary nephrotic syndrome in our research were 8 (2, 16) years. The average duration or interval time from glucocorticoid medication use to eye adverse effects was 157 (6, 420) days. No statistical significance was found in intraocular pressure between different genders, types of glucocorticoid, different route of glucocorticoid and whether methylprednisolone pulse treatment (P>0.05). There was no significant correlation between age, body mass index, blood pressure, cumulative dosage, duration time of glucocorticoid, mean daily dosage and glucocorticoid-induced ocular hypertension (P>0.05). The ocular hypertension was controlled after treatment., Conclusion: Children with nephrotic syndrome after treatment of glucocorticoid are susceptible to ocular complications, and the occurrence of ocular hypertension is closely related to glucocorticoid susceptibility of the nephrotic children. Regular eye monitor is indispensable for the children suffering from primary nephrotic syndrome.

Objective: Tacrolimus prolonged-release(PR) formulation is a new once-daily formulation of the calcineurin inhibitor tacrolimus, which is currently used in adult liver or kidney transplant patients,and is also gradually widely used in children with nephrotic syndrome.The present study was undertaken to preliminarily investigate the pharmacokinetic characteristics of tacrolimus PR in pediatric nephrotic syndrome recipients., Methods: This single-center open-label prospective study was performed in pediatric nephrotic syndrome recipients. Pharmacokinetic samples were collected from eight pediatric subjects with nephrotic syndrome from Department of Pediatric Nephrology in Peking University First Hospital between June and August 2011. They followed administration of single oral doses of tacrolimus PR formulation at 0.02 mg/kg (n=2), 0.05 mg/kg (n=2) and 0.10 mg/kg (n=4). Blood samples were taken before the dose and 1, 2, 4, 6, 8, 10, 12 and 24 h after drug intake. No other medicines or interacting food or drinks were taken during the study period. Blood concentrations were measured using an enzyme multiplied immunoassay technique. Pharmacokinetic analysis was performed using WinNolin Phoenix software Version 6.0(Pharsight, Cary, NC,USA)., Results: The pharmacokinetic data were best described by a non-compartment model. Pharmacokinetic parameters of tacrolimus PR formulation in the 3 ascending doses groups (0.02 mg/kg,0.05 mg/kg and 0.10 mg/kg) were as follows: the maximum drug concentrations (C max /D) were (1.7±1.0) μg/L, (3.1±1.9) μg/L, (8.0±3.5) μg/L, respectively; Areas under the drug concentration-time curve(AUC 0-∞ /D) were (47.2±47.1) h×μg/L, (84.0±13.1) h×μg/L, (175.6±107.1) h×μg/L, respectively; Oral clearance rates were (0.8±0.9) L/(h×kg), (0.4±0.1) L/(h×kg), (1.9±1.3) L/(h×kg), respectively; Body weight normalized distribution volumes were (7.0±3.4) L/kg, (12.4±8.4) L/kg and (73.6±68.6) L/kg, respectively. Both mean C max normalized level for the administered dose(C max /D) and mean AUC 0-∞ normalized level for the administered dose (AUC 0-∞ /D) were higher in the 0.05 mg/kg dosage group than in the 0.02 and 0.10 mg/kg dosage group. There were two peaks in the drug concentrations in every dose group;a primary peak appeared at the end of about 2 h followed by a small secondary peak at h 12, which was more noticeable in the 0.10 mg/kg dose group than in the two lower dosages., Conclusion: The pharmacokinetic characteristics of tacrolimus PR formulation were initially explored in pediatric patients with nephritic syndrome. The data presented form a basis for subsequent larger scale studies on pharmacokinetics of tacrolimus PR formulation in nephritic syndrome children.

Objective: To study the clinical features of congenital syphillis presenting congenital nephrotic syndrome (CNS) in children., Methods: Two cases diagnosed as congenital syphillis presenting CNS in our hospital were retrospectively analyzed and related data reviewed., Results: The two children had edema, gross proteinuria, haematuria, hepatosplenomegaly, abdominal distention and anaema. Rapid plasmin regain (RPR) and treponema palidum hemagglutination assay (TPHA) were all positive. One chiild was also had renal biopsy and showed membraous nephropathy. Adequate penicillin therapy got satisfatory effects without steroid treatment., Conclusion: For children with early occurrence of proteinuria, edema accompanied by anaema, and hepatosplenomegaly, we should conside the possibility of syphillis nephropathy, which should be treated with enough dosage of penicillin in instead of steroid. Early diagnosis and treatmen could get complete recovery of CNS.

Objective: Acute kidney injury (AKI) was recently proposed for early recognition of renal function impairment and prompt interventions. Previous study revealed that AKI was highly associated with the prognosis. However, there was rare report of AKI in renal diseases, especially in children cohorts. Therefore, we performed the prospective clinical research in children with renal diseases in our hospital, aiming to study the prevalence, the clinical characteristics and the short-term prognosis of AKI., Method: The study was designed as a prospective, single-center observational study., Inclusion Criteria: (1) the primary diagnosis was primary nephrotic syndrome (NS), Henoch-Schoenlein purpura nephritis (HSPN) or lupus nephritis (LN), (2) the duration from the onset of the renal diseases to the admission was less than 3 months. The serum creatinine and urine output of the subjects would be prospectively monitored. AKI was defined by the adult criteria and stratified by Acute Kidney Injury Network (AKIN) criteria. The patients were followed up at 6 months and 12 months after enrollment., Result: Between October 2007 and April 2009, a total of 95 children were included, including 65 cases with NS, 15 HSPN and 15 LN. Mean age was (8.9 ± 3.9) years (range 2 - 16 years). Thirty-three of the 95 patients (34.7%) fulfilled the AKI criteria, 13 patients (13.7%) were diagnosed as acute renal failure (ARF). All the AKI in children with LN and HSPN presented with serum creatinine elevation. However, 65.4% of AKI in NS presented with decreasing urine output, only 19.2% accompanied with increasing creatinine, with higher stages of urine output. Regarding the etiology, only 26.9% of AKI in NS had definite cause, most of which resulted from side-effect of cyclosporine, hypovolemia or tubule-interstitial damage, independent of glomerular diseases. In contrast, the AKI in LN and HSPN were exclusively caused by glomerular diseases. The length and costs of hospitalization of AKI group were significantly higher than non-AKI [length of hospitalization (d), 28(6 to 94) vs. 21(7 to 100), Z = -1.971, P = 0.049; cost of hospitalization (yuan), 12 035.7 (1561.7 to 94 783.1) vs. 8594.3 (1390.1 to 98 876.5), Z = -1.993, P = 0.046]. There was no significant difference in the serum creatinine at 6-month and 12-month follow-up between AKI group and non-AKI [6-month, (60.4 ± 91.8) µmol/L vs. (42.8 ± 12.2) µmol/L, t = 0.937, P = 0.358; 12-month, (48.7 ± 18.1) µmol/L vs. (47.7 ± 14.2) µmol/L, t = 0.197, P = 0.845]., Conclusion: The prevalence of AKI (34.7%) was higher than that of ARF (13.7%) in children with renal diseases. Most of the AKI in NS resulted from non-glomerular diseases. In contrast, most AKI in LN and HSPN were caused by underlying glomerular diseases. The length and costs of hospitalization were significantly higher in AKI group. However, there was no significant difference in serum creatinine between AKI and non-AKI group in the follow-up at 6 months and 12 months. Further investigations on criteria for the diagnosis of AKI in children with renal diseases are still needed.

Objective: To analyze the clinical features and WT1 gene mutations in patients with steroid-resistant nephrotic syndrome (SRNS) accompanied with genitourinary malformations. The expression of podocyte molecules was also investigated in renal specimen of these WT1 mutated patients., Methods: From January 2005 to May 2007, 3 cases of SRNS accompanied with genitourinary malformations were involved in this study. The expression of podocyte molecules (nephrin, podocin, alpha-actinin 4, WT1 and CD2AP) in 2 cases was analyzed by immunofluorescence and immunohistochemistry; using PCR to amplify genomic DNA and RT-PCR to amplify WT1 cDNA. GeneScan and GeneScan software were used to quantify the ratio of +KTS/-KTS isoforms., Results: The age of onset of the 3 cases were 6 months, 1 year and 10 years, respectively. The age at diagnosis was 7 months, 9 years and 15 years, respectively. The phenotype of case 1 and case 3 was male accompanied with genitourinary malformations. Case 2 was phenotypic female. Karyotype analysis of the 3 cases revealed 46, XY. Each case was diagnosed as SRNS. Focal segmental glomerulosclerosis (FSGS) was confirmed in 2 cases. Podocyte molecular expression altered in renal tissues of 2 cases. WT1 staining was negative in case 1. WT1 expression in case 2 showed a diffuse nuclear staining with less obvious speckles compared with controls. WT1 IVS 9 + 5 G > A mutation was detected in case 2 and WT1 exon 9 1186 G > A mutation was detected in case 3. No WT1 mutation was detected in case 1., Conclusions: Karyotype analysis and WT1 genetic analyzing should be performed for all female patients with early onset SRNS and in male patients with SRNS accompanied with genitourinary malformations. The abnormal ratio of +KTS/-KTS isoforms caused by WT1 mutations along with abnormal expression of podocyte molecules were involved in the pathogenesis of proteinuria.

Objective: To understand WT1 mutations in patients with steroid resistant nephrotic syndrome (SRNS) accompanied with genitourinary malformations., Methods: Three cases of SRNS accompanied with genitourinary malformations were enrolled. The expression of podocyte molecules (nephrin, podocin, alpha-actinin-4, WT1, and CD2AP) in 2 cases was analyzed with the immunofluorescence and immunohistochemistry techniques. The genomic DNA and cDNA of WT1 were analyzed by using PCR and RT-PCR, respectively. GeneScan and GeneScan software were used to quantify the ratio of +KTS/-KTS isoforms., Results: The onset ages of 3 cases were 6 months, 1 year, and 10 years old, respectively. The diagnosis age was 7 months, 9 years, and 15 years old, respectively. The phenotype of Case 1 and Case 3 was male accompanied with genitourinary malformations. Case 2 was phenotypic female. Karyotype analysis of 3 cases revealed 46, XY. Three cases were diagnosed as SRNS. Focal segmental glomerulosclerosis (FSGS) was confirmed in 2 cases. Podocyte molecular expression altered in renal tissues of 2 cases. In addition, WT1 staining was negative in Case 1. WT1 expression in Case 2 showed diffuse nuclear staining with less obvious speckles compared with controls. WT1 IVS 9 +5 G>A mutation was detected in Case 2 and WT1 Exon 9 1186 G>A mutation was detected in Case 3. No WT1 mutation was detected in Case 1., Conclusion: Karyotype analysis and WT1 genetic testing should be done in all female patients with early onset steroid resistant FSGS and in male patients with SRNS accompanied with genitourinary malformations. Abnormal podocyte molecular expression suggests that more podocyte molecules might be involved in the pathogenesis of proteinuria in WT1 mutational patients.

Objective: The nephrotic syndrome is defined by heavy proteinuria, edema, hypoalbuminemia, and hyperlipidemia. Idiopathic nephrotic syndrome (INS) mainly occurs in children, which is generally treated with glucocorticoids. The majority of patients are steroid-sensitive (SSINS) while steroid-resistance occurs in a subset of NS children (SRINS). Although intensive efforts have been undertaken to study the associations between SRINS and renal pathological changes, pharmacokinetics, and the GR density and binding affinity, the mechanisms underlying steroid-resistance are still not elucidated entirely. The authors hypothesized that it might be associated with polymorphisms in the glucocorticoid receptor gene (NR3C1). The study aimed to screen the NR3C1 gene for polymorphisms in genomic DNA samples from SRINS, SSINS children and control group, and to analyze the association of the polymorphisms in the NR3C1 gene and SRINS of children., Methods: Totally 39 SRINS and 67 SSINS children (81 males and 25 females with the mean age of 7 years) were involved in the study. Umbilical cord blood of 62 normal neonates and peripheral blood of 2 healthy volunteers were selected as controls. Genomic DNA was isolated from peripheral blood lymphocytes of all subjects. All the NR3C1-coding exons and intron-flanking portions were amplified by polymerase chain reaction (PCR). For polymorphism screen, PCR products were analyzed by denaturing high performance liquid chromatography (DHPLC). DNA fragments with aberrant elution profiles were re-amplified and sequenced directly., Results: Twelve aberrant elution profiles were identified with DHPLC in SRINS, SSINS and controls. Among them, 6 previously reported polymorphisms and 6 novel polymorphisms were confirmed by sequencing (198G > A, 200G > A, IVSD-16G > T, 1896C > T, 2166C > T, 2430T > C; novel, 1206C > T, 1374A > G, IVSG-68&#95;IVSG-63delAAAAAA, 2193T > G, IVSH-9C > G, 2382C > T), and 3 groups of SNPs were in complete linkage disequilibrium, which resulted in 3 different haplotypes ([198G > A + 200G > A], [1374A > G + IVSG-68&#95;IVSG-63delAAAAAA + IVSH-9C > G + 2382C > T], [1896C > T + 2166C > T + 2430T > C]). The last two genotypes were first reported. The genotype frequencies of the 2 novel haplotypes were 10.3% vs 1.5% in SRINS and SSINS, and 15.4% vs 7.5% in SRINS and SSINS, respectively. Other polymorphisms were relatively rare detectable both in patients and controls., Conclusion: Twelve polymorphisms in the NR3C1 gene were detected with the technique of DHPLC, of which six polymorphisms were identified at the first time. Two types of newly found haplotypes were associated with steroid-resistant idiopathic nephrotic syndrome of children, which might be responsible for steroid-resistance in partial idiopathic nephrotic syndrome of children.