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The prognosis of acute kidney injury (AKI) varies in children with nephrotic syndrome (NS), data on factors predicting the recovery and recurrence of AKI in children with NS are limited. This study aimed to explore the possible factors predicting the recovery from and recurrence of AKI in children with primary NS. Children with primary NS complicated with AKI from 1993 to 2017 in a single centre were reviewed retrospectively. The clinical pictures and possible factors predicting the recovery from and recurrence of AKI in children with primary NS were investigated. Sixty-eight episodes of AKI in 59 children with NS were analysed: 88.2% of AKI recovered within 3 months, and 2.9% of AKI did not recover after 3 months. Survival analysis revealed that leucocyturia is significantly related to the AKI recovery time (P = 0.001), and children with leucocyturia [22 (4, 79) days] recovered significantly slower than did children without leucocyturia [12.0 (2, 39) days]. Renal tubular and interstitial injury were prominent in children with leucocyturia, and 11.9% of children with index AKI experienced the recurrence of AKI. Most episodes of AKI that occurred in children with NS recovered completely. Leucocyturia is a significant factor predicting the recovery time of AKI.

To explore the genetic etiology and clinical outcome of a child with steroid-resistant nephrotic syndrome and diffuse mesangial sclerosis.Genomic DNA was extracted from peripheral blood leukocytes of the proband and his parents. Targeted capture - next generation sequencing and Sanger sequencing were carried out. Candidate variant was verified by segregation analysis in his family.A heterozygous missense variant of the TRPC6 gene, namely c.325GA (p.Gly109Ser), was detected in the proband. The same variant was not detected in either parent. According to the guidelines for the interpretation of sequence variants developed by American College of Medical Genetics and Genomics, the variant was predicted as pathogenic.The missense variant of the TRPC6 gene probably underlay the diffuse mesangial sclerosis in this patient. Above finding has expanded the phenotypic spectrum of the TRPC6 gene.

Background cblC deficiency is the most common type of methylmalonic aciduria in China. Late-onset patients present with various non-specific symptoms and are usually misdiagnosed. The purpose of this study is to investigate the clinical features of patients with late-onset cblC deficiency and explore diagnosis and management strategies around puberty. Results This study included 56 patients (35 males and 21 females) with late-onset cblC deficiency who were admitted to our clinic between 2002 and September 2021. The diagnosis was confirmed by metabolic and genetic tests. The clinical and biochemical features, disease triggers, outcome, and associated genetic variants were examined. The onset age ranged from 10 to 20 years (median age, 12 years). Fifteen patients (26.8%) presented with symptoms after infection or sports training. Further, 46 patients (82.1%) had neuropsychiatric diseases; 11 patients (19.6%), cardiovascular diseases; and 6 patients (10.7%), pulmonary hypertension. Renal damage was observed in 6 cases (10.7%). Genetic analysis revealed 21 variants of the MMACHC gene in the 56 patients. The top five common variants detected in 112 alleles were c.482G > A (36.6%), c.609G > A (16.1%), c.658_660delAAG (9.8%), c.80A > G (8.0%), and c.567dupT (6.3%). Thirty-nine patients carried the c.482G > A variant. Among 13 patients who exhibited spastic paraplegia as the main manifestation, 11 patients carried c.482G > A variants. Six patients who presented with psychotic disorders and spastic paraplegia had compound heterozygotic c.482G > A and other variants. All the patients showed improvement after metabolic treatment with cobalamin, l-carnitine, and betaine, and 30 school-aged patients returned to school. Two female patients got married and had healthy babies. Conclusions Patients with late-onset cblC deficiency present with a wide variety of neuropsychiatric symptoms and other presentations, including multiple organ damage. As a result, cb1C deficiency can easily be misdiagnosed as other conditions. Metabolic and genetic studies are important for accurate diagnosis, and metabolic treatment with cobalamin, l-carnitine, and betaine appears to be beneficial.

BackgroundThromboembolism 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.MethodsThe 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.ResultsWe 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.ConclusionsThrombosis 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.

Pediatric native kidney diseases are common worldwide. The pathological diagnosis of kidney lesions is crucial for clinical treatment and prognosis. The aim of the current study was therefore to evaluate the value of electron microscopy (EM) to the final diagnosis of native kidney biopsies in children.A retrospective evaluation of 855 pediatric kidney biopsies obtained from the Department of Pediatrics in Peking University First Hospital between November 2010 and December 2017 was performed to assess the contribution of EM to the final diagnosis.The role of EM in the final diagnosis was determined to be crucial in 300 cases (35.1%), important in 280 cases (32.7%), and auxiliary in 275 cases (32.2%). EM is considered most valuable in a large percentage of glomerular diseases, mainly including minimal change disease, early-stage membranous nephropathy, postinfectious glomerulonephritis, Alport syndrome, thin basement membrane nephropathy, and thrombotic microangiopathy. EM also provided helpful diagnostic information in cases of focal segmental glomerulosclerosis, lupus nephritis, IgA nephropathy, and IgA vasculitis (Henoch-Schonlein purpura nephritis). Additionally, EM was crucial in 90.0% of cases of subtle pathological changes observed with light microscopy (LM) and immunofluorescence (IF) and in 69.3% of the IF-negative specimens. Patients with nephrotic syndrome or hematuria also benefit from ultrastructural examination.The present study demonstrated the crucial or important role of EM in the diagnosis of a majority of native kidney biopsies in children. The application of EM should be integrated together with LM and IF as a routine method of assessing pediatric kidney specimens. Graphical abstract.

Background To characterize the phenotypic spectrum and assess the antialbuminuric response to angiotensin converting enzyme (ACE) inhibitor and/or angiotensin receptor blocker (ARB) therapy in a cohort of children with Dent disease. Methods The patients’ clinical findings, renal biopsy results, genetic and follow‐up data were analyzed retrospectively. Mutations in CLCN5 or OCRL were detected by next‐generation sequencing or Sanger sequencing. Results Of 31 Dent disease boys, 24 carried CLCN5 and 7 carried OCRL mutations. Low molecular weight proteinuria and albuminuria were detected in all cases. Nephrotic‐range proteinuria and severe albuminuria were identified in 52% and 62% of cases, respectively; by 7 years of age, 6 patients had hematuria and nephrotic‐range proteinuria, and 7 patients had hematuria and moderate to severe albuminuria. In addition to disease‐related renal features, patients with Dent‐1 disease also presented with congenital cataract (1/9) and developmental delay (2/7). Seventeen of 31 patients underwent renal biopsy. Glomerular changes included mild glomerular lesions, mesangial proliferative glomerulonephritis and focal segmental glomerular sclerosis. Thirteen of the 31 patients had follow‐up records and received ACE inhibitor and/or ARB treatment for more than 3 months. After a median 1.7 (range 0.3–8.5) years of treatment, a reduction in the urinary microalbumin‐to‐creatinine ratio was observed in 54% of children. Conclusions Hematuria with nephrotic‐range proteinuria or moderate to severe albuminuria was common in Dent disease patients. Extrarenal manifestations were observed in Dent‐1 patients, which extends the phenotypic spectrum. In addition, ACE inhibitors and ARBs are well tolerated, and they are partially effective in controlling albuminuria., Hematuria with nephrotic‐range proteinuria or moderate to severe albuminuria was common in Dent disease patients.Patients with Dent‐1 disease may also present with congenital cataract and developmental delay.The percentage of urinary albumin in the total protein ranged from 24.2% to 47.6%; it was usually smaller than that of LMW proteinuria. ACE inhibitors and ARBs are partially effective in controlling albuminuria and they are well tolerated.

Background Alport syndrome is a rare hereditary kidney disease manifested with progressive renal failure. Considerable variation exists in terms of disease progression among patients with Alport syndrome. Identification of patients at high risk of rapid progression remains an unmet need. Urinary epidermal growth factor (uEGF) has been shown to be independently associated with risk of progression to adverse kidney outcome in multiple independent adult chronic kidney disease (CKD) cohorts. In this study, we aim to assess if uEGF is associated with kidney impairment and its prognostic value for children with Alport syndrome. Methods One hundred and seventeen pediatric patients with Alport syndrome and 146 healthy children (3–18 years old) were included in this study. uEGF was measured in duplicates in baseline urine samples using ELISA (R&D) and concentration was normalized by urine creatinine (uEGF/Cr). In patients with longitudinal follow-up data (n = 38), progression was defined as deteriorated kidney function (CKD stage increase) during follow-up period (follow-up length is about 31 months in average). The association of baseline uEGF/Cr level with estimated glomerular filtration rate (eGFR) slope and Alport syndrome patients’ progression to a more advanced CKD stage during the follow-up period was used to evaluate the prognostic value of the marker. Results We found that uEGF/creatinine (uEGF/Cr) decreases with age in pediatric patients with Alport syndrome with a significantly faster rate than in healthy children of the same age group. uEGF/Cr is significantly correlated with eGFR (r = 0.75, p

The widely used International Study of Kidney Disease in Children (ISKDC) classification for Henoch-Schonlein purpura nephritis (HSPN) does not completely correlate with the clinical presentation and long-term prognosis of this disease. Primary IgA nephropathy (IgAN) and HSPN share common features; thus, the Oxford classification of IgAN might be useful in predicting the long-term outcomes of HSPN. However, its value has not been confirmed in children with HSPN. We selected children with HSPN diagnosed between 2003 and 2015, and reclassified their renal biopsies according to the Oxford classification scoring system. The primary outcome was impaired renal function, and remission of proteinuria and clinical remission were secondary outcomes. We included 104 patients (58 males, 46 females) with a median age of 10 (4–17) years. Mesangial hypercellularity (M1) was strongly associated with proteinuria, and tubular atrophy/interstitial fibrosis (T1&2) and C2 (with crescents in > 25% of glomeruli) were associated with reduced estimated glomerular filtration rate (eGFR) at the time of biopsy. Patients with M1, endocapillary proliferation (E1), segmental glomerulosclerosis (S1), and crescents (C1&2) were more likely to have been treated with high-dose methylprednisolone. At univariate time-dependent analyses, S1 was strongly associated with the primary outcome (p = 0.025), whereas T1&2 was significantly negatively associated with proteinuria remission (p = 0.035) and clinical remission (p = 0.038). Our findings suggest that the Oxford classification is valid for children with HSPN. S and T lesions, which are ignored in the ISKDC classification, can be used to assess renal outcomes of HSPN, and such assessments are not affected by currently available treatments. The value of M, E and C lesions in predicting response to therapy and renal outcome warrants further study.

The aim of this study was to elucidate whether genetic screening test results of pediatric patients with steroid-resistant nephrotic syndrome (SRNS) vary with ethnicity.Using high-throughput DNA sequencing, 28 nephrotic syndrome-related genes were analyzed in 110 chil-dren affected by SRNS and 10 children with isolated proteinuria enrolled by 5 centers in China (67 boys, 53 girls). Their age at disease onset ranged from 1 day to 208 months (median, 48.8 months). Patients were excluded if their age at onset of disease was over 18 years or if they were diagnosed as having Alport syndrome.A genetic etiology was identified in 28.3% of our cohort and the likelihood of establishing a genetic diagnosis decreased as the age at onset of nephrotic syndrome increased. The most common mutated genes were ADCK4 (6.67%), NPHS1 (5.83%), WT1 (5.83%), and NPHS2 (3.33%), and the difference in the frequencies of ADCK4 and NPHS2 mutations between this study and a study on monogenic causes of SRNS in the largest international cohort of 1,783 different families was significant. A case of congenital nephrotic syndrome was attributed to a homozygous missense mutation in ADCK4, and a de novo missense mutation in TRPC6 was detected in a case of infantile nephrotic syndrome.Our results showed that, in the first and the largest multicenter cohort of Chinese pediatric SRNS reported to date, ADCK4 is the most common causative gene, whereas there is a low prevalence of NPHS2 mutations. Our data indicated that the genetic testing results for pediatric SRNS patients vary with different ethnicities, and this information will help to improve management of the disease in clinical practice.

Background The aim of this study was to analyze the diverse phenotypes of children with PAX2‐related disorder so as to improve our understanding of this disease. Methods The clinical data of ten children with PAX2 mutations, detected by targeted region capture sequencing or whole‐exome sequencing, were retrospectively analyzed. Family members of index cases were verified by Sanger sequencing and family segregation analysis was performed. Results The age of first symptom of 10 unrelated children (six girls and four boys) was 6.4 (ranged from postnatal day to 14.8) years old. Proteinuria, abnormal renal function, and structure were found in all patients. Renal hypoplasia and renal cysts were found in 10 of 10 and five of 10 cases, respectively. Three patients progressed to chronic kidney disease stage 5 and the onset age of end‐stage renal disease was 9.8–16.4 years old. PAX2‐related ocular abnormalities were found in five of seven cases and three patients were observed to have more than one ocular findings involved. In addition to diverse renal and ocular findings, new phenotypes including congenital ventricular septal defect, skeletal deformity (fourth metatarsal microsomia), ovarian teratoma, and relatively rare extrarenal manifestations such as growth retardation, gout, and microcephaly were also found. Three novel mutations were reported for the first time. De novo mutations occurred in all patients who were carried out segregation analysis. Patients with the same mutation had different manifestations. PAX2‐related disorder showed remarkable clinical variability and phenotypic heterogeneity. Conclusion We firstly reported skeletal deformity (fourth metatarsal microsomia), ovarian teratoma, and congenital ventricular septal defect as new phenotypes of PAX2‐related disorder which enlarged the phenotypic spectrum. Gout was firstly reported as the onset symptom of PAX2‐related disorder. The diagnosis of PAX2‐related disorder should be considered without family history due to a much higher percentage of De novo mutations.

Background Alport syndrome is an inherited renal disease caused by mutations in COL4A3, COL4A4, or COL4A5 genes. Coexisting mutations in either two of the three genes in Alport patients have been reported recently. However, the effect of heterozygous mutations in COL4A3 or COL4A4 genes in X‐linked Alport syndrome (XLAS) patients is unclear. Methods Using targeted next‐generation sequencing, six unrelated Chinese children were identified to have a combination of a pathogenic variant in COL4A5 and a heterozygous mutation in COL4A3 or COL4A4. They were three males and three females. Another three XLAS males each with only one pathogenic variant in COL4A5 were included. The clinical data were analyzed and compared between the males in two groups (group 1, males with a pathogenic variant in COL4A5 and a heterozygous pathogenic variant in COL4A3 or COL4A4; group 2, males with only one pathogenic variant in COL4A5). Results Patients with XLAS who also had heterozygous pathogenic COL4A3 or COL4A4 variants accounted for 1% of Alport syndrome. In this study, three children showed coexisting pathogenic variants in COL4A5 and COL4A3. Two children showed pathogenic variants in COL4A5 and COL4A4. One child had pathogenic variants in the three COL4A3‐5 genes, in which the pathogenic variant in COL4A5 was de novo and the pathogenic variants in COL4A4 and COL4A3 were inherited independently (in trans). The site and type of mutations in COL4A5 were similar between the two groups. It was revealed that males in group 1 presented more severe proteinuria than males in group 2 (p

Objectives The aims of this study were to investigate the population pharmacokinetic (PPK) characteristics of tacrolimus in Chinese children with nephrotic syndrome and to apply it in clinical practice. Materials and methods A total of 137 concentrations from 61 patients were collected from routine therapeutic drug monitoring data between 2011 and 2018. Population modeling was performed with the nonlinear mixed-effects model (NONMEM) program, using a one-compartment model with first-order absorption and elimination. The mean population estimate values of clearance (CL/F) and volume of distribution (V/F) were determined. Common demographic and clinical variables were tested for their influence on these parameters. External validation was conducted, and Monte Carlo simulation, based on the final model, was carried out to determine optimal dosage regimen. Results Age and body weight were the covariates that displayed a significant influence on CL/F and V/F according to the final regression model. Goodness-of-fit plots, bootstrap outcomes, and external validation confirmed the relatively good stability and prediction capability of the model. The interindividual variability of CL/F was 31.10%, and the residual variability was 0.91 ng/mL. Mean prediction error (MPE, %) and Mean absolute prediction error (MAPE, %) were 10.3% and 16.6%, respectively. Monte Carlo simulation based on the final model was carried out to determine optimal dosage regimen. Conclusion A PPK model of tacrolimus in children with nephrotic syndrome was developed. Age and bodyweight could partly explain the interindividual variability in the CL/F and V/F of tacrolimus. The final model could be used to accurately predict tacrolimus individual pharmacokinetic parameters and assist in dosage optimization. .

Atypical hemolytic uremic syndrome (aHUS) is associated with defective complement regulation. Anti-complement factor H (CFH) antibodies were thought to participate in the pathogenesis of aHUS. The aim of this study was to address the functions and properties of CFH autoantibodies in a Chinese Han cohort of aHUS patients. Thirty-six anti-CFH antibody-positive aHUS patients at the acute phase of the disease were involved in this study. Clinical data of the patients were collected. Anti-CFH immunoglobulin G (IgG) subclasses and antibody isotypes were detected by ELISA. Epitope mapping was performed using recombinant CFH fragments (SCRs 1–4, SCR 7, SCRs 11–14, and SCRs 19–20). Purified IgG from plasma from seven patients were used for functional analyses. All patients presented with the classic triad of HUS. The anti-CFH autoantibodies mostly bound to the SCRs 19–20 domains of CFH but not the SCRs 1–4 domains. CFI cofactor activity was not disturbed by the anti-CFH antibody in any of the seven patients. Purified IgG interfered with the binding of CFH to C3b and CFH-mediated sheep erythrocyte protection in all seven patients. IgG from 4/5 (80%) patients tested inhibited the binding of CFH to glomerular endothelial cells. Our study suggests that the properties of CFH antibodies from patients with aHUS, including the recognition of SCRs and IgG subclasses, can influence and impair the biological role of CFH and therefore contribute to aHUS susceptibility.

The aim of this study was to analyze the long-term efficacy and safety of angiotensin-converting enzyme inhibitor (ACEi) and ACEi + angiotensin receptor blocker (ARB) treatments in a cohort of children with Alport syndrome (AS). This was a respective review of 79 Chinese children with AS who received ACEi alone or combined ACEi + ARB therapy. The mean age of the pediatric patients with AS at onset of treatment was 8.6 ± 4.1 (range 1.5–16.3) years. The mean duration of follow-up was 2.5 ± 1.8 (range 0.5–7.8) years. For analysis, we separated the children into three groups according to proteinuria level before treatment, namely

The TTC21B gene is now known as causative of nephronophthisis-related ciliopathies (NPHP-RC). We reported two Chinese paediatric cases with end-stage renal disease and other phenotypes caused by the TTC21B gene mutations.The clinical features of Chinese paediatric cases with NPHP-RC were summarized. Mutation analysis of the TTC21B gene was performed using next-generation sequencing.The two cases both had nephrotic proteinuria, renal failure, hypertension and abnormal liver function (or hepatic fibrosis). One case also presented situs inversus and short phalanges. They developed end-stage renal disease (ESRD) at 1 year old and 8 years old, respectively, when renal pathology both showed focal segmental glomerular sclerosis (FSGS) with tubulointerstitial lesions including interstitial fibrosis and atrophic tubules. Three novel disease-causing TTC21B mutations were identified. One case carried homozygous mutation c.2211 + 3A G, while the other case carried compound heterozygous mutations c.1552 T C (p.C518R) and c.1456dupA (p.R486KfsX22).Mutations in TTC21B cause a range of ciliopathy phenotypes in humans. We identified 3 novel TTC21B mutations in two Chinese paediatric cases that both presented end-stage renal disease and other different features. This is the first TTC21B mutations ever reported in China.

Anti-complement factor H (CFH) autoantibody-associated hemolytic uremic syndrome (HUS) is a severe sub-type of HUS. We assessed the clinical and renal pathological features, circulating complement levels, and genetic background of Chinese pediatric patients with this sub-type of HUS. Thirty-three consecutive patients with acute kidney injury who tested positive for serum anti-CFH autoantibodies were enrolled in this study. All of the eight patients who underwent renal biopsies presented with changes typical of thrombotic microangiopathy, especially changes in chronic characteristics. Compared to patients in remission and normal control subjects, patients with acute disease had significantly lower plasma CFH levels and significantly higher plasma complement 3a (C3a), C5a, and terminal complement complex (SC5b-9) levels. The CFH–anti-CFH immunoglobin G (IgG) circulating immunocomplex (CFH-CIC) titers were more closely correlated with CFH plasma levels than anti-CFH IgG levels. Of the 22 patients, four (18%) were homozygous for CFHR3–1Δ and ten were heterozygous for CFHR1 or CFHR3 deletions. Most patients responded well to a combination of plasma and immunosuppressive therapies, with a remission rate of 87%. At the end of the follow-up, nine patients reached the combined end-points, including two with end-stage renal disease and seven with relapses. Plasma C3a, C5a, and SC5b-9 levels predicted disease activity in anti-CFH autoantibody-associated HUS patients enrolled in this study. These patients responded well to plasma therapy combined with immunosuppression.

To analyze the clinical and genetic features of X-linked Alport syndrome (XLAS) in men positive for the collagen α5(Ⅳ) chain in epidermal basement membrane.This was a retrospective study. Totally 725 families were diagnosed as Alport syndrome in Department of Pediatrics of Peking University First Hospital during January 1998 to December 2014, among them 450 patients were males with XLAS. Patients who met both of the following two criteria were included in this study. (1)Patients underwent α5(Ⅳ) chain staining in the epidermal basement membrane. (2)Mutations in COL4A5 gene were detected.Mann-Whitney test and χ(2) test were used.Totally 140 males with XLAS were included in this study, 18 cases were α5 (Ⅳ)-positive and 122 cases were α5 (Ⅳ)-negative. The two groups of patients were compared, the median age at analysis was 11.0 vs. 7.2 years (Z = -1.839, P = 0.066), the 24-hour urine protein was 1.50 vs. 0.57 g/d (Z = -1.212, P = 0.226), the rate of hearing loss was 28% vs. 53% (χ(2) = 3.619, P = 0.067), the number of patients progressed to end stage renal disease (ESRD) was 4 vs. 12 (χ(2) =2.377, P = 0.128), the median age of ESRD was 31.0 vs. 16.6 years (Z = -2.554, P = 0.011), the rate of missense mutations in COL4A5 gene was 67% vs. 52% (χ(2) = 1.424, P = 0.313).Compared the two groups of patients with positive and negative staining for the collagen Ⅳ α5 chain in epidermal basement membrane, there was no significant difference in the proteinuria level, the rate of hearing loss and genotype of COL4A5 gene. But the patients with positive staining progressed to ESRD significantly later than the patients with negative staining.

IgA nephropathy is the most common type of glomerulonephritis in the world. Its clinical and pathological manifestations vary. A few of the patients with IgA nephropathy present with rapidly progressive glomerulonephritis (RPGN) and/or crescent formation. Their conditions are serious and acute, but there are few reports on their characteristics, treatment and outcome. This study aimed to analyze the clinicalopathological features, treatment and prognosis of primary IgA nephropathy in children, to provide a reference for clinical diagnosis and treatment.A retrospective study was conducted in children with primary IgA nephropathy with crescent formation and/or rapidly progressive glomerulonephritis admitted to our department from 2000 to 2014. The patients meeting the inclusion and exclusion criteria were included. Patients were divided into RPGN group and non-RPGN group according to the clinical manifestations, crescent formation group and non-crescent group, crescentic IgA nephropathy group and non-crescentic IgA nephropathy group according to renal biopsy. Their clinical manifestations and pathological features, treatment and prognosis were compared.A total of 265 patients were recruited, 10 patients (3.8%) had RPGN, 151 patients (57.0%) had crescent formation, 19 cases (7.2%) showed crescentic IgA nephropathy.Compared with non-RPGN group, RPGN group showed more gross hematuria, higher serum creatinine, lower creatinine clearance correction at biopsy and follow-up, and more crescentic IgA nephropathy (P0.05). The percent of patients who received methylprednisolone pulse and blood purification therapy in RPGN group is higher than that of non-RPGN group (P0.05). Compared with non-crescent group, crescent formation group showed more gross hematuria at biopsy and follow-up, higher serum creatinine at biopsy, lower creatinine clearance correction, more 24-hour urinary protein at biopsy and higher serum creatinine at follow-up (P0.05). The percentage of patients received more methylprednisolone pulse, oral steroids, cyclophosphamide pulse in crescent formation group was higher than that of non-crescent group (P0.05). Compared with non-crescentic IgA nephropathy group, crescentic IgA nephropathy group showed more RPGN percent, higher serum creatinine, more 24-hour urinary protein at biopsy (P0.05). The percentage of patients who received more methylprednisolone pulse and blood purification therapy in crescentic IgA nephropathy group was more than non-crescentic IgA nephropathy group (P0.05). At follow-up, 20.0% of the patients with RPGN and crescent nephritis returned to normal renal function and the percent of crescent glomerulonephritis but not RPGN was 71.4%, RPGN but not crescent glomerulonephritis was 80.0%, crescent formation but not crescent nephritis was 87.5%.In primary IgA nephropathy with crescent formation and/or rapidly progressive glomerulonephritis, the patients with both RPGN and crescentic IgA nephropathy showed the worst clinical manifestations, its prognosis was worst while the patients with crescent formation showed the mildest clinical manifestations and best prognosis.

We report on a Chinese girl with Frasier syndrome (FS). She presented with steroid-resistant focal segmental glomerulosclerosis (FSGS) and male pseudohermaphroditism. The WT1 IVS 9 + 5 GA mutation was detected in one allele in the proband. The ratio of +KTS/-KTS was 0.67 in the proband's cDNA. The expression of podocyte molecules (WT1, nephrin, podocin, alpha-actinin 4 and CD2AP) were also investigated in a renal specimen of this FS patient. WT1 expression showed diffuse nuclear staining, with less obvious speckles in the patient's glomeruli than in those of controls. The distribution and intensity of podocyte molecules were altered both in normal- and abnormal-appearing glomeruli. In conclusion, the study presented a case of FS by clinical manifestation, renal pathology, karyotype analysis and genetic testing. A lower ratio of +KTS/-KTS and an abnormal distribution of WT1, as well as abnormal expressions of other podocyte molecules, were also revealed. The mechanisms of WT1 mutation causing FS still need to be investigated.

To analyze the relationship between hyperuricemia and primary nephrotic syndrome in childhood.A retrospective study was carried out in 107 children with primary nephrotic syndrome. The clinical data were analyzed with statistical methods to identify the related factors with hyperuricemia.The morbidity of hyperuricemia in children with primary nephrotic syndrome was 45% (48/107). Compared to those in normal serum uric acid group, the incidence of hypertension (33%, 16/48), serum triglyceride [2.59(1.62-3.87) mmol/L], creatinine [43.85(33.38-56.38)mmol/L], urea [6.11(3.77-8.40)mmol/L] and blood uric acid/creatinine ratio [9.30(7.03-12.72)] increased while creatinine clearance rate [141.74(103.57-160.97)ml/(min·1.73 (2))] decreased in hyperuricemia group.Hyperuricemia in children with primary nephrotic syndrome correlated with the increase of serum creatinine, urea and blood uric acid/creatinine ratio, the decrease of creatinine clearance rate and the occurance of hypertension.

To investigate the clinical characteristics, renal pathology, treatment and prognosis of children with atypical hemolytic uremic syndrome associated with H factor antibody.Four children less than 18 yr of age admitted from Nov. 2010 to May 2011 in Peking University First Hospital were included. They all met the criteria for atypical hemolytic uremic syndrome and with positive serum anti factor H antibody. They aged from 5 to 11 yr. Data on clinical manifestations, renal pathology, treatment and prognosis were analyzed.All of the 4 cases had gastrointestinal symptoms such as vomiting, abdominal pain, or abdominal distension. None of them had diarrhea. Two children had hypertension. One child had episodes of convulsion. One child had history of atypical hemolytic uremic syndrome. All of them had low serum complement C3. Three of them had low serum factor H (38.0, 88.4, 209.4 mg/L). All of them had serum antibody to factor H (1: 7 068, 1: 1 110, 1: 174, and 1: 869). Three of them received renal biopsy, all of them showed thrombotic microangiopathy. All of them were treated with steroid combined with mycophenolate mofetil. Two children received plasma exchange. They were followed up for 8 to 29 months. The renal function became normal and proteinuria relieved in all of them. The serum factor H concentration increased to 405.8, 155.8 and 438.4 mg/L, respectively. The titer of anti factor H antibody decreased to 1: 119, 1: 170, 1: 123, and 1: 674, respectively.Gastrointestinal symptom is common in children with atypical hemolytic uremic syndrome associated with H factor antibody. Hypocomplementemia was observed in all of them. Steroid combined with mycophenolate mofetil seemed to be effective for them. The monitoring of serum factor H and antibody to factor H may help diagnosis and treatment.

Autosomal recessive Alport syndrome (ARAS) results from mutations in the COL4A3 or COL4A4 gene. We analyzed the genotype and phenotype of 17 unrelated Chinese patients with ARAS. Clinical data were reviewed. All coding exons of COL4A3 and COL4A4 genes were PCR-amplified and sequenced from genomic DNA. We identified pathologic mutations in all patients, giving a mutation detection rate of 100%, with 82% in COL4A3 gene and 18% in COL4A4 gene. Sixteen novel mutations in COL4A3 gene and four novel mutations in COL4A4 gene were identified. Furthermore, a previously reported in-frame deletion mutation (40_63del24) in exon 1 of the COL4A3 gene was found in four patients in our study. A single 40_63del24 mutation in COL4A3 seems to result in mild or no renal manifestations, whereas the homozygous state of 40_63del24 in COL4A3 gene or compound heterozygous mutation of 40_63del24 plus another nonsense or frameshift mutation in COL4A3 gene seems to result severe ARAS with hearing loss. Half of the probands' parents had hematuria with or without mild proteinuria. Therefore, we recommend that ARAS be considered when a patient has a positive family history of hematuria, and screening for COL4A3 mutations firstly may be an efficient strategy for molecular diagnosis of ARAS.

Previous studies have demonstrated that the genetic variations of glucocorticoid receptor gene (NR3C1) are associated with both familial steroid resistance and acquired steroid resistance in some diseases, such as Cushing's disease, leukemia, lupus nephritis, and female pseudohermaphroditism. In this study, we examined the genetic variations of NR3C1 in 35 children with sporadic steroid-resistant nephrotic syndrome (SRNS), and in 83 cases with sporadic steroid-sensitive NS (SSNS) using polymerase chain reaction, denaturing high-performance liquid chromatography and DNA sequencing, and analyzed possible associations between NR3C1 variants and steroid resistance in sporadic NS. No causative mutations were found; however, six previously identified and six novel polymorphisms, 1206C > T, 1374A > G, 2382C > T, 2193T > G, IVS7-68_-63delAAAAAA, and IVS8-9C > G, were detected. Two novel haplotypes, [1374A > G; IVS7-68_-63delAAAAAA; IVS8-9C > G; 2382C > T] and [1896C > T; 2166C > T; 2430T > C], of NR3C1 were also identified in sporadic NS and controls. The odds ratios (95% Confidence Interval) for the two novel NR3C1 haplotypes in the sporadic nephrotic children at risk of steroid resistance were 4.970 (0.889-27.788) and 2.194 (0.764-6.306), respectively, but the association between NR3C1 haplotypes and steroid resistance was not significant. Further studies on the possible association between the two novel NR3C1 haplotypes and steroid resistance in sporadic NS in larger cohorts are required.

Background. Since the identification of the NPHS2 gene, various investigators have demonstrated that an NPHS2 mutation is a frequent cause of sporadic steroid-resistant nephrotic syndrome (SRNS), and occurs in 10.5–28% of children with the syndrome. Idiopathic nephrotic syndrome (INS) is also the most frequent glomerular disease in Chinese children, of which � 20% of cases show steroid resistance. To our knowledge, however, whether or not NPHS2 is the causative gene in Chinese sporadic SRNS has not been established. This study aims to examine mutations in NPHS2 in Chinese children with sporadic SRNS. Methods. We examined 23 Chinese children with sporadic SRNS for mutations in NPHS2. The mutational analysis of NPHS2 was performed by polymerase chain reaction, denaturing high-performance liquid chromatography and DNA sequencing. Results. A heterozygous missense mutation of L361P in exon 8 of NPHS2 was detected in one of 23 children with sporadic SRNS, whereas it was not found in 53 controls. We also identified seven NPHS2 polymorphisms, � 51G>T, 288C>T, IVS3-46C>T, IVS321C>T, IVS7-74G>C, 954T>C and 1038A>G, in some patients and controls. There was no significant difference in the genotypic and allelic frequencies of these polymorphisms between the patients and controls. Conclusion. The results demonstrate that NPHS2 mutations are also present in Chinese sporadic SRNS. Our investigation supports the necessity of searching for mutations in NPHS2 in Chinese children with sporadic SRNS.