Are children with IgA nephropathy different from adult patients?

BACKGROUND: Previously, several studies have indicated that pediatric IgA nephropathy (IgAN) might be different from adult IgAN, and treatment strategies might be also different between pediatric IgAN and adult IgAN. METHODS: We analyzed two prospective cohorts established by pediatric and adult nephrologists, respectively. A comprehensive analysis was performed investigating the difference in clinical and pathological characteristics, treatment, and prognosis between children and adults with IgAN. RESULTS: A total of 1015 children and 1911 adults with IgAN were eligible for analysis. More frequent gross hematuria (88% vs. 20%, p < 0.0001) and higher proteinuria (1.8 vs. 1.3 g/d, p < 0.0001) were seen in children compared to adults. In comparison, the estimated glomerular filtration rate (eGFR) was lower in adults (80.4 vs. 163 ml/min/1.73 m2, p < 0.0001). Hypertension was more prevalent in adult patients. Pathologically, a higher proportion of M1 was revealed (62% vs. 39%, p < 0.0001) in children than in adults. S1 (62% vs. 28%, p < 0.0001) and T1-2 (34% vs. 8%, p < 0.0001) were more frequent in adults. Adjusted by proteinuria, eGFR, and hypertension, children were more likely to be treated with glucocorticoids than adults (87% vs. 45%, p < 0.0001). After propensity score matching, in IgAN with proteinuria > 1 g/d, children treated with steroids were 1.87 (95% CI 1.16-3.02, p = 0.01) times more likely to reach complete remission of proteinuria compared with adults treated with steroids. CONCLUSIONS: Children present significantly differently from adults with IgAN in clinical and pathological manifestations and disease progression. Steroid response might be better in children.

New Criterion to Evaluate Acute-on-Chronic Kidney Injury Based on the Creatinine Reference Change.

BACKGROUND: The lack of consensus criteria of acute on chronic kidney injury (ACKI) affects the judgment for its clinical prognosis. METHODS: In this study, we analyzed the data from 711,615 hospitalized adults who had at least 2 serum creatinine (SCr) tests within 30 days. We estimated the reference change value (RCV) of SCr given initial SCr level in adults without known risks of acute kidney injury other than chronic kidney disease (CKD). We proposed a criterion for ACKI based on the RCV of SCr (cROCK), which defined ACKI as a ≥25% increase in SCr in 7 days. We validated cROCK by its association with the risks of in-hospital mortality, death after discharge, and CKD progression in a large cohort of patients with CKD stage 3. RESULTS: In 21,661 patients with CKD stage 3, a total of 3,145 (14.5%), 1,512 (7.0%), and 221 (1.0%) ACKI events were detected by both cROCK and Kidney Disease Improving Global Outcomes (KDIGO), cROCK only, and KDIGO only, respectively. cROCK detected 40% more ACKI events than KDIGO. Compared with patients without ACKI by both definitions, those with cROCK- but not KDIGO-defined ACKI had a significantly increased risk of in-hospital mortality (hazard ratio [HR] 5.53; 95% CI 3.75-8.16), death after discharge (HR 1.51; 95% CI 1.21-1.83), and CKD progression (OR 5.65; 95% CI 3.05-10.48). CONCLUSIONS: RCV-based criterion (cROCK) for ACKI is clinically valid in that it has a substantially improved sensitivity in identifying patients with high risk of adverse outcomes.

A New Criterion for Pediatric AKI Based on the Reference Change Value of Serum Creatinine.

BACKGROUND: Current definitions of AKI do not take into account serum creatinine's high variability in children. METHODS: We analyzed data from 156,075 hospitalized children with at least two creatinine tests within 30 days. We estimated reference change value (RCV) of creatinine on the basis of age and initial creatinine level in children without kidney disease or known AKI risk, and we used these data to develop a model for detecting pediatric AKI on the basis of RCV of creatinine. We defined pediatric AKI according to pediatric reference change value optimized for AKI in children (pROCK) as creatinine increase beyond RCV of creatinine, which was estimated as the greater of 20 µmol/L or 30% of the initial creatinine level. RESULTS: Of 102,817 children with at least two serum creatinine tests within 7 days, 5432 (5.3%) had AKI as defined by pROCK compared with 15,647 (15.2%) and 10,446 (10.2%) as defined by pediatric RIFLE (pRIFLE) and Kidney Disease Improving Global Outcomes (KDIGO), respectively. Children with pROCK-defined AKI had significantly increased risk of death (hazard ratio, 3.56; 95% confidence interval, 3.15 to 4.04) compared with those without AKI. About 66% of patients with pRIFLE-defined AKI and 51% of patients with KDIGO-defined AKI, mostly children with initial creatinine level of <30 µmol/L, were reclassified as non-AKI by pROCK, and mortality risk in these children was comparable with risk in those without AKI by all definitions. CONCLUSIONS: pROCK criterion improves detection of "true" AKI in children compared with earlier definitions that may lead to pediatric AKI overdiagnosis.

A genomic association study revealing subphenotypes of childhood steroid-sensitive nephrotic syndrome in a larger genomic sequencing cohort.

Dissecting the genetic components that contribute to the two main subphenotypes of steroid-sensitive nephrotic syndrome (SSNS) using genome-wide association studies (GWAS) strategy is important for understanding the disease. We conducted a multicenter cohort study (360 patients and 1835 controls) combined with a GWAS strategy to identify susceptibility variants associated with the following two subphenotypes of SSNS: steroid-sensitive nephrotic syndrome without relapse (SSNSWR, 181 patients) and steroid-dependent/frequent relapse nephrotic syndrome (SDNS/FRNS, 179 patients). The distribution of two single-nucleotide polymorphisms (SNPs) in ANKRD36 and ALPG was significant between SSNSWR and healthy controls, and that of two SNPs in GAD1 and HLA-DQA1 was significant between SDNS/FRNS and healthy controls. Interestingly, rs1047989 in HLA-DQA1 was a candidate locus for SDNS/FRNS but not for SSNSWR. No significant SNPs were observed between SSNSWR and SDNS/FRNS. Meanwhile, chromosome 2:171713702 in GAD1 was associated with a greater steroid dose (>0.75 mg/kg/d) upon relapse to first remission in patients with SDNS/FRNS (odds ratio = 3.14; 95% confidence interval, 0.97-9.87; P = 0.034). rs117014418 in APOL4 was significantly associated with a decrease in eGFR of greater than 20% compared with the baseline in SDNS/FRNS patients (P = 0.0001). Protein-protein intersection network construction suggested that HLA-DQA1 and HLA-DQB1 function together through GSDMA. Thus, SSNSWR belongs to non-HLA region-dependent nephropathy, and the HLA-DQA/DQB region is likely strongly associated with disease relapse, especially in SDNS/FRNS. The study provides a novel approach for the GWAS strategy of SSNS and contributes to our understanding of the pathological mechanisms of SSNSWR and SDNS/FRNS.

Risk factors for renal outcomes in children with antineutrophil cytoplasmic antibody-associated vasculitis: a nationwide retrospective study in China.

BACKGROUND: Pediatric antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a life-threatening systemic vasculitis featured by liability to renal involvement. However, there are few studies on the risk factors and predictive models for renal outcomes of AAV in children. METHODS: Data from 179 AAV children in multiple centers between January 2012 and March 2020 were collected retrospectively. The risk factors and predictive model of end-stage renal disease (ESRD) in AAV were explored. RESULTS: Renal involvement was the most typical manifestation (95.5%), and the crescent was the predominant pathological lesion (84.9%). The estimated glomerular filtration rate (eGFR) was evaluated in 114 patients, of whom 59.6% developed ESRD, and the median time to ESRD was 3.20 months. The eGFR [P = 0.006, odds ratio (OR) = 0.955, 95% confidence interval (CI) = 0.924-0.987] and the percentages of global glomerulosclerosis (pGGS; P = 0.018, OR = 1.060, 95% CI = 1.010-1.112) were independent risk factors for ESRD of renal biopsy. Based on the pGGS and eGFR at renal biopsy, we developed three risk grades of ESRD and one predictive model. The Kaplan‒Meier curve indicated that renal outcomes were significantly different in different risk grades (P < 0.001). Compared with serum creatinine at baseline, the predictive model had higher accuracy (0.86 versus 0.58, P < 0.001) and a lower coefficient of variation (0.07 versus 0.92) in external validation. CONCLUSIONS: Renal involvement is the most common manifestation of pediatric AAV in China, of which more than half deteriorates into ESRD. The predictive model based on eGFR at renal biopsy and the pGGS may be stable and accurate in speculating the risk of ESRD in AAV children. Supplementary file 2 (MP4 18937 KB).

Lipid metabolism contribute to the pathogenesis of IgA Vasculitis.

BACKGROUND AND OBJECTIVES: The underlying mechanism of IgA vasculitis (IgAV) and IgA vasculitis with nephritis (IgAVN) remains unclear. Therefore, there are no accurate diagnostic methods. Lipid metabolism is related to many immune related diseases, so this study set out to explore the relationship of lipids and IgAV and IgAVN. METHODS: Fifty-eighth patients with IgAV and 28 healthy controls were recruited, which were divided into six separate pools to investigate the alterations of serum lipids according to the clinical characteristics: healthy controls group (HCs) and IgAV group (IgAVs), IgAVN group (IgAV-N) and IgAV without nephritis group (IgAV-C), initial IgAV group (IgAV0) and IgAV in treatment with glucocorticoids group (IgAV1). RESULTS: 31 identified lipid ions significantly changed in IgAVs with p < 0.05, variable importance of the projection (VIP) > 1 and fold change (FC) > 1.5. All these 31 lipid ions belong to 6 classes: triacylglycerols (TG), phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylserine, ceramide, and lysophosphatidylcholine. TG (16:0/18:1/22:6) +NH4 over 888875609.05, PC (32:1) +H over 905307459.90 and PE (21:4)-H less than 32236196.59 increased the risk of IgAV significantly (OR>1). PC (38:6) +H was significantly decreased (p < 0.05, VIP>1 and FC>1.5) in IgAVN. PC (38:6) less than 4469726623 conferred greater risks of IgAV (OR=45.833, 95%CI: 6.689~341.070). CONCLUSION: We suggest that lipid metabolism may affect the pathogenesis of IgAV via cardiovascular disease, insulin resistance, cell apoptosis, and inflammation. The increase of TG(16:0/18:1/22:6) + NH4, and PC(32:1) + H as well as PE (21:4)-H allow a good prediction of IgAV. PE-to-PC conversion may participate in the damage of kidney in IgAV. PC (38:6) + H may be a potential biomarker for IgAVN.

Association between HLA alleles and sub-phenotype of childhood steroid-sensitive nephrotic syndrome.

BACKGROUND: Few studies have addressed the effects of human leukocyte antigen (HLA) alleles on different clinical sub-phenotypes in childhood steroid-sensitive nephrotic syndrome (SSNS), including SSNS without recurrence (SSNSWR) and steroid-dependent nephrotic syndrome/frequently relapse nephrotic syndrome (SDNS/FRNS). In this study, we investigated the relationship between HLA system and children with SSNSWR and SDNS/FRNS and clarified the value of HLA allele detection for precise typing of childhood SSNS. METHODS: A total of 241 Chinese Han individuals with SSNS were genotyped using GenCap-WES Capture Kit, and four-digit resolution HLA alleles were imputed from available Genome Wide Association data. The distribution and carrying frequency of HLA alleles in SSNSWR and SDNS/FRNS were investigated. Additionally, logistic regression and mediating effects were used to examine the relationship between risk factors for disease process and HLA system. RESULTS: Compared with SSNSWR, significantly decreased serum levels of complement 3 (C3) and complement 4 (C4) at onset were detected in SDNS/FRNS (C3, P < 0.001; C4, P = 0.018). The average time to remission after sufficient initial steroid treatment in SDNS/FRNS was significantly longer than that in SSNSWR (P = 0.0001). Low level of C4 was further identified as an independent risk factor for SDNS/FRNS (P = 0.008, odds ratio = 0.174, 95% confidence interval 0.048-0.630). The HLA-A*11:01 allele was independently associated with SSNSWR and SDNS/FRNS (P = 0.0012 and P = 0.0006, respectively). No significant HLA alleles were detected between SSNSWR and SDNS/FRNS. In addition, a mediating effect among HLA-I alleles (HLA-B*15:11, HLA-B*44:03 and HLA-C*07:06), C4 level and SDNS/FRNS was identified. CONCLUSIONS: HLA-I alleles provide novel genetic markers for SSNSWR and SDNS/FRNS. HLA-I antigens may be involved in steroid dependent or frequent relapse in children with SSNS as mediators of immunoregulation.

The Clinical and Genetic Features in Chinese Children With Steroid-Resistant or Early-Onset Nephrotic Syndrome: A Multicenter Cohort Study.

Steroid-resistant nephrotic syndrome (SRNS) is one of the major causes of end-stage kidney disease (ESKD) in children and young adults. For approximately 30% of children with SRNS results from a genetic cause. In this study, genotype-phenotype correlations in a cohort of 283 pediatric patients with SRNS or early-onset NS (nephrotic syndrome presenting within the first year of life) from 23 major pediatric nephrology centers in China were analyzed. All patients were performed with next-generation sequencing and Sanger sequencing. The overall mutation detection rate was 37.5% (106 of 283 patients). WT1 was the most frequently detected mutation, followed by NPHS1, NPHS2, and ADCK4, and these four major causative genes (WT1, NPHS1, NPHS2, and ADCK4) account for 73.6% of patients with monogenic SRNS. Thirteen of 106 individuals (12.3%) carried mutations in ADCK4 that function within the coenzyme Q10 biosynthesis pathway. In the higher frequently ADCK4-related SRNS, two mutations, c.737G>A (p.S246N) and c.748G>C (p.D250H), were the most prevalent. Our study provides not only definitive diagnosis but also facilitate available targeted treatment for SRNS, and prediction of prognosis and renal outcome. Our indications for genetic testing are patients with FSGS, initial SRNS, cases of positive family history or those with extra-renal manifestations.

Whole-exome sequencing of a multicenter cohort identifies genetic changes associated with clinical phenotypes in pediatric nephrotic syndrome.

Understanding the association between the genetic and clinical phenotypes in children with nephrotic syndrome (NS) of different etiologies is critical for early clinical guidance. We employed whole-exome sequencing (WES) to detect monogenic causes of NS in a multicenter cohort of 637 patients. In this study, a genetic cause was identified in 30.0% of the idiopathic steroid-resistant nephrotic syndrome (SRNS) patients. Other than congenital nephrotic syndrome (CNS), there were no significant differences in the incidence of monogenic diseases based on the age at manifestation. Causative mutations were detected in 39.5% of patients with focal segmental glomerulosclerosis (FSGS) and 9.2% of those with minimal change disease (MCD). In terms of the patterns in patients with different types of steroid resistance, a single gene mutation was identified in 34.8% of patients with primary resistance, 2.9% with secondary resistance, and 71.4% of children with multidrug resistance. Among the various intensified immunosuppressive therapies, tacrolimus (TAC) showed the highest response rate, with 49.7% of idiopathic SRNS patients achieving complete remission. Idiopathic SRNS patients with monogenic disease showed a similar multidrug resistance pattern, and only 31.4% of patients with monogenic disease achieved a partial remission on TAC. During an average 4.1-year follow-up, 21.4% of idiopathic SRNS patients with monogenic disease progressed to end-stage renal disease (ESRD). Collectively, this study provides evidence that genetic testing is necessary for presumed steroid-resistant and idiopathic SRNS patients, especially those with primary and/or multidrug resistance.

Integrated Analyses of Gut Microbiome and Host Metabolome in Children With Henoch-Schönlein Purpura.

Recent studies have shown that intestinal microbes and metabolites are involved in the pathogenesis of many diseases. However, whether and how they are related to Henoch-Schönlein purpura (HSP) has yet to be understood. This work is designed to detect gut microbes, intestinal and serum metabolites in children with HSP, trying to discover the etiology and pathogenesis of HSP. A total of 86 children were recruited in this study, namely, 58 children with HSP (HSP group) and 28 healthy children as control groups (CON group). 16S rDNA amplicon sequencing technology and UPLC-QTOF/MS non-targeted metabolomics analysis were used to detect the intestinal microbes and metabolites, and also multi-reaction monitoring technology for detecting serum arachidonic acid (AA) and its metabolites. Then, correlation analysis was performed to explore the possible interaction between the differential gut microbes and metabolites. As a result, at the microbiota family level, the CON group had an advantage of Coriobacteriaceae while the HSP group had a dominant Bacteroidaceae. Five kinds of bacteria in the HSP group were significantly enriched at the genus level, and seven kinds of bacteria were significantly enriched in the CON group. A total of 59 kinds of gut metabolites significantly differ between the two groups, in which most are lipids and peptides. Spearman correlation analysis showed that Bacteroides, Dialister, and Agathobacter were associated with unsaturated fatty acids, especially AA metabolism. Then, we tested the AA related metabolites in serum and found thromboxane B2, leukotriene B4, prostaglandin D2, 9S-hydroxyoctadecadienoic acid, and 13S-hydroxyoctadecadienoic acid significantly changed. In conclusion, children with HSP had dominant Bacteroidaceae and decreased Coriobacteriaceae in the family level of gut microbes, and also lipids and peptides changed most in the gut metabolites. Our data suggested that the biosynthesis and metabolism of unsaturated fatty acids, especially AA and its metabolites, might participate in the occurrence and development of HSP.

Correlation Analysis between Gut Microbiota and Metabolites in Children with Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune-mediated diffuse connective tissue disease characterized by immune inflammation with an unclear aetiology and pathogenesis. This work profiled the intestinal flora and faecal metabolome of patients with SLE using 16S RNA sequencing and gas chromatography-mass spectrometry (GC-MS). We identified unchanged alpha diversity and partially altered beta diversity of the intestinal flora. Another important finding was the increase in Proteobacteria and Enterobacteriales and the decrease in Ruminococcaceae among SLE patients. For metabolites, amino acids and short-chain fatty acids were enriched when long-chain fatty acids were downregulated in SLE faecal samples. KEGG analysis showed the significance of the protein digestion and absorption pathway, and association analysis revealed the key role of 3-phenylpropanoic acid and Sphingomonas. Sphingomonas were reported to be less abundant in healthy periodontal sites of SLE patients than in those of HCs, indicating transmission of oral species to the gut. This study contributes to the understanding of the pathogenesis of SLE disease from the perspective of intestinal microorganisms, explains the pathogenesis of SLE, and serves as a basis for exploring potential treatments for the disease.

Abnormalities of Serum Fatty Acids in Children With Henoch-Schönlein Purpura by GC-MS Analysis.

Purpose: The objectives of this work were to test the levels of serum medium- and long- chain fatty acids (MLCFAs) in children and to discover their possible relationship with Henoch-Schönlein Purpura (HSP), also known as Immunoglobulin A vasculitis. Methods: A total of 57 children with HSP (HSP group) and 28 healthy children (CON group) were recruited for this study. Serum specimens were collected to detect the compositions and contents of MLCFAs by gas chromatography with mass spectrometry (GC-MS) analysis. Results: The contents of all detected 37 MLCFAs in the HSP group were higher than the healthy group. Thirty-one species of MLCFAs were discovered to have a significant difference (p < 0.05) in two groups. Comparing to healthy controls, there were 31, 31, 18 fatty acids showed a statistical difference in the untreated group, regular treated group, and withdrawal group of HSP, respectively. The trend of fatty acids in the three HSP groups was similar to the healthy controls, as well as the untreated group and regular treated group changed more obviously than the withdrawal group. Almitate (C16:0) and 18 carbon atoms (C18) of fatty acids were abundant in all three HSP groups, divided according to the treatment of glucocorticoid. Some fatty acids were found having considerable differences (p < 0.05) in three groups. Monounsaturated fatty acids (MUFAs), including elaidate (C18:1T), cis-11,14,17-eicosatrienoic acid ester (C20:1), and cis-15-tetracosenoate (C24:1), were distinctly higher in HSP children with renal damage. Conclusion: Our study revealed that the abnormalities in MLCFA may be associated with the development of HSP. Another interesting finding was that fatty acids contents were changing during the glucocorticoid treatment. Meanwhile, long-chain MUFAs may have an impact on renal damage in HSP patients. Further studies need to be carried out in order to explore the specific mechanism of fatty acids in the course of HSP.

Proton pump inhibitors and the risk of hospital-acquired acute kidney injury in children.

BACKGROUND: To evaluate the association between use of proton pump inhibitor (PPI) and the risk of hospital-acquired acute kidney injury (HA-AKI) in hospitalized children. METHODS: We conducted a multicenter retrospective cohort study in hospitalized children aged 1 month to 18 years from 25 tertiary hospitals across China from 2013 to 2015. Patient-level data were obtained from the electronic hospitalization databases. AKI was defined and staged using the serum creatinine (SCr) data according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. RESULTS: Among 42,232 children analyzed, 11,496 (27.2%) used PPI, 1,760 (4.2%) used histamine 2 receptor antagonist (H2RA), and 3,514 (8.3%) had HA-AKI during hospitalization. Over 85% of PPIs were prescribed for prophylaxis of gastro-duodenal lesions in children. The use of PPI was associated with a significantly increased risk of HA-AKI compared with both non-users [odds ratio (OR), 1.37; 95% confidence interval (CI), 1.23-1.53)] and H2RA users (OR, 1.24; 95% CI, 1.01-1.52). The associations were consistent across children of different age range, gender, subtypes of PPIs and methods of administration. A larger effect was observed in children with chronic kidney disease (OR, 3.37; 95% CI, 2.46-4.62) and those needed intensive care (OR, 1.54; 95% CI, 1.33-1.78). The risk of HA-AKI was increased even within the recommended dosage range of PPI. CONCLUSIONS: PPIs were widely used and associated with an increased risk of HA-AKI in hospitalized children in China.

[Expression of glomerular heparan sulfate domains in pediatric patients with minimal change nephrotic syndrome].

OBJECTIVES: To investigate the expression of glomerular heparin sulfate (HS) in paediatric patients with minimal change nephritic syndrome (MCNS). METHODS: The kidyney tissues were collected by biopsy from 13 paediatric patients with MCNS, while 5 normal renal biopsy samples were used as control. HS in glomeruli was analysed by indirect immunofluorescence staining using four different monoclonal antibodies, Hepss1, 3G10, JM403 and 10E4, which all recognize distinct HS species and each interacts with a specific HS domain. The concentrations of urine heparan sulfate also were measured by enzyme-linked immunosorbent assay (Elisa). RESULTS: Expression of HS fine domains was aberrant in paediatric patients compared with control subjects. Children with MCNS in replase showed a decreased glomerular expression of 10E4, JM403 and Hepss1 (P < 0.05). The level of urinary HS was significantly increased in peadiatric patients with MCNS when compared with that in control subjects (P < 0.01). CONCLUSION: These results suggest that loss of heparan sulphate in renal tissue may play a role in the pathogenesis of MCNS proteinuria.

[A prospective multicenter clinical control trial on treatment of refractory nephrotic syndrome with mycophenolate mofetil in children].

OBJECTIVE: To evaluate the efficacy and safety of mycophenolate mofetil (MMF) plus prednisone on refractory nephrotic syndrome (RNS) in children. METHODS: One hundred and forty-two children with RNS from ten clinical trial centers were divided into two groups: MMF (n=87) and control (n=55). The MMF group patients were administered with oral MMF (30-40 mg/kg daily) for at least 6 months. Afterwards the patients who responded to MMF received another 6 months MMF treatment at a dosage of 10-20 mg/kg daily. The controls were treated with pulse intravenous infusion of cyclophosphamide (CTX) (10 mg/kg daily) for 2 days every 2 weeks for 3 months. Then CTX was administered at a dosage of 500 mg/m2 once a month 4, 7 and 10 months after treatment. While the patients received MMF or CTX treatment, they were treated with oral prednisone (0.5-1 mg/kg daily) for 2 to 3 months, and then the dosage of prednisone was gradually reduced. Urinary protein, liver and renal functions, and side effects of drugs were examined at regular intervals for one year. RESULTS: Of the 87 patients, 58 achieved complete remission, 16 achieved partial remission, 9 achieved early remission and 4 had no response to treatment. In the control group, 35 achieved complete remission, 9 achieved partial remission, 1 achieved early remission and 10 had no response to treatment. The total remission rate in the MMF group (95.4%) was significantly higher than that in the control group (81.8%) (P<0.01). After treatment 67 patients (65.4%) in the MMF group had negative proteinuria compared with 36 patients (65.4%) in the control group (P>0.05). MMF was found to be more effective in reducing proteinuria, and improving hypoproteinemia, oliguria, hyperlipemia, and edema than CTX. MMF was better tolerated with lower incidences of adverse reactions than CTX. CONCLUSIONS: The combined therapy of MMF and prednisone is more effective and tolerable than pulse intravenous infusion of CTX for treatment of RNS in children.

Acute Kidney Injury among Hospitalized Children in China.

BACKGROUND AND OBJECTIVES: High-quality epidemiologic data on AKI in children are particularly lacking in developing countries. This study aimed to assess the epidemiology and clinical correlates of AKI among hospitalized children in China. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a multicenter study, in a cohort of hospitalized children aged 1 month to 18 years, from 25 general and children's hospitals in China during 2013-2015. We obtained patient-level data from the electronic hospitalization information system and laboratory databases of all children who had at least two serum creatinine tests within any 7-day window during their first 30 days of hospitalization. We identified AKI events according to the creatinine criteria of Kidney Disease Improving Global Outcomes. The in-hospital outcomes of AKI, including mortality, kidney recovery, and length of stay, were assessed. We estimated the corresponding hazard ratios using a Cox proportional hazard model, with adjustment for age, sex, comorbidities, and clinical procedures. RESULTS: A total of 19,908 (20%) patients with AKI were identified among 101,836 pediatric inpatients, of which 7220 (7%) were community acquired and 12,688 (13%) were hospital acquired. Up to 96% of these AKI events were not diagnosed on the discharge records. The cumulative incidence of AKI in infants (28%) was twice that in adolescents (12%). The profiles of risk factors differed between community-acquired and hospital-acquired AKI and varied with age. Diarrhea and sepsis were the top risk factors for community-acquired AKI, each contributing 6% of the risk. Congenital heart disease/cardiac surgery was the major risk factor for hospital-acquired AKI, contributing to 19% of cases. Exposure to nephrotoxic drugs, mostly nonsteroidal anti-inflammatory drugs and proton pump inhibitors, was common in hospitalized children and was associated with a higher risk of AKI. Death occurred in 842 out of 19,908 patients (4%) with AKI versus 450 out of 81,478 children (0.5%) without AKI. The risk of in-hospital death was higher among children with severe AKI, shock, and respiratory failure. Pediatric AKI was associated with longer hospital stay and higher daily cost, even after adjustment for covariates. CONCLUSIONS: Pediatric AKI is common and is substantially underdiagnosed in China.

Characterization of the genomic structures and selective expression profiles of nine class I small heat shock protein genes clustered on two chromosomes in rice (Oryza sativa L.).

The cytosolic class I small heat shock proteins (sHSP-CI) represent the most abundant sHSP in plants. Here, we report the characterization and the expression profile of nine members of the sHSP-CI gene family in rice (Oryza sativa Tainung No.67), of which Oshsp16.9A, Oshsp16.9B, Oshsp16.9C, Oshsp16.9D and Oshsp17.9B are clustered on chromosome 1, and Oshsp17.3, Oshsp17.7, Oshsp17.9A and Oshsp18.0 are clustered on chromosome 3. Oshsp17.3 and Oshsp18.0 are linked by a 356-bp putative bi-directional promoter. Individual gene products were identified from the protein subunits of a heat shock complex (HSC) and from in vitro transcription/ translation products by two-dimensional gel electrophoreses (2-DE). All sHSP-CI genes except Oshsp17.9B were induced strongly after a 2-h heat shock treatment. The genes on chromosome 3 were induced rapidly at 32 and 41 degrees C, whereas those on chromosome 1 were induced slowly by similar conditions. Seven of these genes, except Oshsp16.9D and Oshsp17.9B, were induced by arsenite (As), but only genes on chromosome 3 were strongly induced by azetidine-2-carboxylic acid (Aze, a proline analog) and cadmium (Cd). A similar expression profile of all sHSP-CI genes at a lower level was evoked by ethanol, H2O2 and CuCl2 treatments. Transient expression assays of the promoter activity by linking to GUS reporter gene also supported the in vivo selective expression of the sHSP-CI genes by Aze treatment indicating the differential induction of rice sHSP-CI genes is most likely regulated at the transcriptional level. Only Oshsp16.9A abundantly accumulated in mature dry seed also suggested additionally prominent roles played by this HSP in development.