Application of the updated International IgA Nephropathy Prediction Tool in children one or two years post-biopsy.

The pediatric International IgA Nephropathy (IgAN) Prediction Tool comprises two models with and without ethnicity and is the first method to predict the risk of a 30% decline in estimated glomerular filtration rate (eGFR) or kidney failure in children at the time of biopsy using clinical risk factors and Oxford MEST histology scores. However, it is unknown if the Prediction Tool can be applied after a period of observation post-biopsy. Using an international multi-ethnic cohort of 947 children with IgAN, 38% of whom were followed into adulthood, the Prediction Tool was updated for use one year after biopsy. Compared to the original pediatric Prediction Tool, the updated post-biopsy Prediction Tool had a better model fit with higher R2D (51%/50% vs 20%), significant increase in 4-year C-statistics (0.83 vs 0.73/0.69, ΔC 0.09 [95% confidence interval 0.07-0.10] and ΔC 0.14 [0.12-0.15]) and better 4-year calibration with lower integrated calibration indices (0.74/0.54 vs 2.45/1.01). Results were similar after internal validation and when the models were applied two years after biopsy. Trajectories of eGFR after a baseline one year post-biopsy were non-linear and those at higher predicted risk started with a lower eGFR and experienced a more rapid decline over time. In children, eGFR had a variable rate of increase until 15-18 years old and then decreased linearly with a more rapid decline in higher risk groups that was similar to young adults of comparable risk. Thus, the original pediatric Prediction Tool should be used in children at the time of biopsy, and the updated pediatric Prediction Tool should be used to re-evaluate risk one or two years after biopsy.

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.

Glomerular basement membrane ultrastructural changes in a patient with COQ2 glomerulopathy: A case report.

Primary coenzyme Q10 deficiency-1, caused by COQ2 disease-causing variants, is an autosomal recessive disorder, and genetic testing is the gold standard for diagnosing this condition. A Chinese boy with steroid-resistant nephrotic syndrome, focal segmental glomerulosclerosis, and progressive kidney insufficiency was included in the study. Electron microscopy revealed the glomerular basement membrane with irregular thickness and lamellation with diffuse effacement of foot processes in the podocytes, and swollen mitochondria with abnormal cristae in the podocytes. Coenzyme Q10 supplementation started about 3 weeks after the onset of mild kidney dysfunction did not improve the proband's kidney outcome. Proband-only whole-exome sequencing and Sanger sequencing revealed two heteroallelic COQ2 variants: a maternally inherited novel variant c.1013G > A[p.(Gly338Glu)] in exon 6 and a variant of unknown origin c.1159C > T[p.(Arg387*)] in exon 7. Subsequent long-read sequencing demonstrated these two variants were located on different alleles. Our report extends the phenotypic and genotypic spectrum of COQ2 glomerulopathy.

[Clinical and genetic analysis of a child with co-morbid progressive IgA nephropathy and COQ8B-associated glomerulopathy].

OBJECTIVE: To explore the genetic etiology and clinical outcome of a child with co-morbid progressive IgA nephropathy and COQ8B-associated glomerulopathy. METHODS: A child who was admitted to Peking University First Hospital on March 2, 2021 was selected as the study subject. Genomic DNA was extracted from peripheral blood samples from the child and his parents and sister. Whole exome sequencing was carried out, and candidate variant was verified by Sanger sequencing. This study was approved by the Peking University First Hospital (Ethics No. 2016[1029]). RESULTS: The child, a 7-year-old boy who had developed proteinuria 8 months before, was diagnosed with IgA nephropathy (M1E1S1T1C1). With steroid, cyclophosphamide, cyclosporine and angiotensin-converting enzyme inhibitor therapy, partial remission of proteinuria was achieved. However, his serum creatinine level had increased from 53.8 mol/L at the onset of disease to 86.7 mol/L after 3.9 years, along with massive proteinuria. Kidney biopsy still indicated IgA nephropathy (M0E0S1T0C0). The child was found to harbor a homozygous c.737G>A (p.Ser246Asn) missense variant of the COQ8B gene, for which his parents and sister were heterozygous carriers. The variant was predicted to be pathogenic (PS1+PM2_Supporting+PM3+PP3+PP4) based on the guidelines from the American College of Medical Genetics and Genomics. The child was treated with high-dose coenzyme Q10 in combination with steroid and/or mycophenolate mofetil, though his serum creatinine level still increased to 286 mol/L after 7.3 years, which conformed to a chronic kidney disorder with glomerular filtration rate category of G3b. CONCLUSION: The homozygous c.737G>A missense variants of the COQ8B gene probably underlay the progressive kidney dysfunction in this child. For children with IgA nephropathy presenting with atypical clinical manifestations, unsatisfactory therapeutic effect, and/or early onset of kidney function decline, coexistence of other diseases should be suspected.

Urinary epidermal growth factor predicts complete remission of proteinuria in Chinese children with IgA nephropathy.

BACKGROUND: This study investigated the association between urinary epidermal growth factor (EGF) and complete remission (CR) of proteinuria in children with IgA nephropathy (IgAN). METHODS: We included 108 patients from the Registry of IgA Nephropathy in Chinese Children. The urinary EGF at the baseline and follow-up were measured and normalized by urine creatinine (expressed as uEGF/Cr). The person-specific uEGF/Cr slopes were estimated using linear mixed-effects models for the subset of patients with longitudinal data of uEGF/Cr. Cox models were used to analyze the associations of baseline uEGF/Cr and uEGF/Cr slope with CR of proteinuria. RESULTS: Patients with high baseline uEGF/Cr were more likely to achieve CR of proteinuria (adjusted HR 2.24, 95% CI: 1.05-4.79). The addition of high baseline uEGF/Cr on the traditional parameters significantly improved the model fit for predicting CR of proteinuria. In the subset of patients with longitudinal data of uEGF/Cr, high uEGF/Cr slope was associated with a higher likelihood of CR of proteinuria (adjusted HR 4.03, 95% CI: 1.02-15.88). CONCLUSIONS: Urinary EGF may be a useful noninvasive biomarker for predicting and monitoring CR of proteinuria in children with IgAN. IMPACT: High levels of baseline uEGF/Cr (>21.45 ng/mg) could serve as an independent predictor for CR of proteinuria. The addition of baseline uEGF/Cr on the traditional clinical pathological parameters significantly improved the fitting ability for the prediction of CR of proteinuria. Longitudinal data of uEGF/Cr were also independently associated with CR of proteinuria. Our study provides evidence that urinary EGF may be a useful noninvasive biomarker in the prediction of CR of proteinuria as well as monitoring therapeutic response, thus guiding treatment strategies in clinical practice for children with IgAN.

Diagnosis and treatment of IgA nephropathy and IgA vasculitis nephritis in Chinese children.

IgA nephropathy (IgAN) and IgA vasculitis-associated nephritis (IgAVN) are among the most frequent childhood glomerular diseases and are characterized by significant variability in clinical manifestations, pathological presentation and long-term outcomes. IgAVN, alternatively called purpura nephritis, is pathologically indistinguishable from kidney-limited IgAN. In Chinese children, the clinical presentations and pathological manifestations of IgAN and IgAVN are variable. The severity of proteinuria and abnormalities in kidney function and blood pressure of children in China are comparable to those of children in Europe, the USA, and Japan. Compared to Caucasian children and Japanese children, crescents were more common in Chinese children with IgAN or IgAVN. Approximately 10-20% of childhood IgAN or IgAVN progresses to impaired kidney function in China. Since 2007, a series of guidelines on the diagnosis and treatment of pediatric kidney diseases has been published following the principles of evidence-based medicine. However, a large difference exists between the Chinese evidence-based guidelines and the guidelines developed by Kidney Disease: Improving Global Outcomes (KDIGO) in 2021. Chinese children with IgAN or IgAVN were more likely to be treated with steroids or immunosuppressive agents. Further studies exploring the optimal treatment regimen for childhood IgAN or IgAVN are needed in the future.

Genotype and phenotype analysis and transplantation strategy in children with kidney failure caused by NPHP.

BACKGROUND: Nephronophthisis-related ciliopathies (NPHP-RC) have strong genotype and phenotype heterogeneity, and the transplantation strategy of Boichis syndrome is still controversial. Our purpose was to examine associations of genotype and phenotype in children with NPHP-RC and analyze the transplantation strategies of different phenotypes. METHODS: The records of children with NPHP treated at our center from 01/2018 to 03/2021 were retrospectively reviewed. Inclusion criteria were a diagnosis of NPHP, received kidney transplantation, and received whole exome sequencing (WES) or nephropathy gene panel testing. RESULTS: Twenty-nine children with NPHP were included. Nine children (31%) had NPHP1 mutations, and all presented with isolated nephropathy. Eighteen of 20 patients with non-NPHP1 mutations had compound heterozygous mutations, and 70% had extrarenal phenotype. Age at disease presentation (11.2 ± 1.94 years) and the development of kidney failure (12.4 ± 2.70 years) were later in children with NPHP1 mutations than those with non-NPHP1 mutations (5.2 ± 2.83 years and 5.7 ± 2.92 years, respectively). Four of six children with NPHP3 mutations were diagnosed with Boichis syndrome due to liver fibrosis. Isolated kidney transplantation resulted in good outcomes for patients with mild or moderate liver fibrosis without portal hypertension, while cholestasis was common postoperatively and could be resolved with ursodeoxycholic acid. CONCLUSIONS: NPHP1 mutations are the most common in children with NPHP, and the phenotype of NPHP1 mutation is significantly different from that of non-NPHP1 mutation. For NPHP patients with mild to moderate liver fibrosis without portal hypertension, timely treatment of cholestasis could prevent the rapid progression of liver function damage after isolated kidney transplantation. A higher resolution version of the Graphical abstract is available as Supplementary information.

Intraindividual variations of urinary biomarkers in hospitalized children with glomerular diseases: a prospective observational study.

This study aimed to assess the intraindividual variations of urinary biomarkers in hospitalized children with glomerular diseases. Hospitalized children with glomerular diseases participated in the study. For each patient, an overnight (9:00 p.m.-7:00 a.m.) urine was collected, followed by a 24-h urine (classified into four distinct periods: morning 7:00 a.m.-12:00 p.m., afternoon 12:00 p.m.-4:00 p.m., evening 4:00 p.m.-9:00 p.m., and overnight 9:00 p.m.-7:00 a.m.). The concentrations of protein, albumin, N-acetyl-beta-D-glucosaminidase, and epidermal growth factor (EGF) were measured and normalized by three correction factors (creatinine, osmolality, or specific gravity, respectively). Additionally, the 2nd overnight urine sample was grouped into different aliquots according to centrifugation, additives, storage temperature, or delayed processing. Twenty (14 boys, 6 girls) children were enrolled, with an average age of 11.3 years. Among the three correction factors, creatinine-normalized biomarkers provided the best agreements among different periods over 24 h. There were significant diurnal variations during 24 h in the concentrations of urinary protein, albumin, N-acetyl-beta-D-glucosaminidase, and EGF (p = 0.001, p = 0.003, p = 0.003, and p = 0.003, respectively). Evening urine overestimated 24-h urinary protein and albumin, while overnight urine underestimated 24-h urinary albumin. Urinary EGF showed low variability within a day or between the 2 days (coefficients of variation 10.2% and 10.6%, respectively) and excellent agreements (intraclass correlation coefficients > 0.9) with 24-h urinary concentration. Furthermore, urinary EGF was not affected by centrifugation, additives, storage temperature, or delayed processing of urine samples (all p > 0.05).  Conclusion: Given the diurnal variations of urinary biomarkers, urine samples should be collected during the same time period in clinical practice if possible. The results also extend the evidence for urinary EGF as a relatively stable biomarker applied in the future clinical practice. What is Known: • Urinary biomarkers have been widely used or discussed in making diagnoses and therapy regimens and estimating the prognosis of pediatric glomerular diseases. It remains unclear whether their levels would be affected by the time of sample collection, processing methods, and storage conditions in hospitalized children with glomerular diseases. What is New: • The levels of both commonly used biomarkers and novel biomarkers exhibited diurnal variations in hospitalized children with glomerular diseases. • Our results extend the evidence for urinary EGF as a relatively stable biomarker applied in the future clinical practice.

Incidence and cost of haemolytic uraemic syndrome in urban China: a national population-based analysis.

BACKGROUND: Haemolytic uraemic syndrome (HUS) is a severe syndrome that causes a substantial burden for patients and their families and is the leading cause of acute kidney injury in children. However, data on the epidemiology and disease burden of HUS in Asia, including China, are limited. We aimed to estimate the incidence and cost of HUS in China.  METHODS: Data about HUS from 2012 to 2016 were extracted from the Urban Employee Basic Medical Insurance (UEBMI) and Urban Resident Basic Medical Insurance (URBMI) databases. All cases were identified by ICD code and Chinese diagnostic terms. The 2016 national incidence rates were estimated and stratified by sex, age and season. The associated medical costs were also calculated. RESULTS: The crude incidence of HUS was 0.66 per 100,000 person-years (95% CI: 0.35 to 1.06), and the standardized incidence was 0.57 (0.19 to 1.18). The incidence of HUS in males was slightly higher than that in females. The age group with the highest incidence of HUS was patients < 1 year old (5.08, 95% CI: 0.23 to 24.87), and the season with the highest incidence was autumn, followed by winter. The average cost of HUS was 2.15 thousand US dollars per patient, which was higher than the national average cost for all inpatients in the same period. CONCLUSIONS: This is the first population-based study on the incidence of HUS in urban China. The age and seasonal distributions of HUS in urban China are different from those in most developed countries, suggesting a difference in aetiology.

Factors predicting the recovery from acute kidney injury in children with primary nephrotic syndrome.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Most episodes of AKI that occurred in children with NS recovered completely. Leucocyturia is a significant factor predicting the recovery time of AKI.

Analysis of chronic kidney disease among national hospitalization data with 14 million children.

BACKGROUND: The main purpose was to determine basic epidemiological data on CKD among hospitalized pediatric patients in China. METHODS: Data from pediatric inpatients with CKD hospitalized from June 1, 2013 to May 31, 2017 were extracted from the electronic records of HQMS database, which includes over 14 million inpatients. Codes from the 10th revision of the International Classification of Diseases (ICD-10) were used to search the database. RESULTS: A total of 524 primary diseases of CKD were included in this study. In all, there were 278 231 pediatric inpatients with CKD, which accounted for 1.95 % of the 14 250 594 pediatric inpatients registered in the HQMS database. The number of pediatric inpatients with CKD was 67 498 in 2013, 76 810 in 2014, 81 665 in 2015 and 82 649 in 2016, which accounted for 1.93 %, 1.93 %, 1.99 and 2.09 %, respectively, of the total population of pediatric inpatients. The etiology of CKD was secondary nephrosis in 37.95 % of cases, which ranked first and followed by CAKUT with a percentage of 24.61 %. Glomerular diseases and cystic kidney disease accounted for 21.18 and 5.07 %, respectively. Among all 278 231 patients, 6 581 (2.37 %) had a primary discharge diagnosis of CKD. The renal pathology findings of CKD showed that IgA accounted for 51.17 %. CONCLUSIONS: This study provides a descriptive analysis of the hospitalized population of pediatric CKD patients. Our study provides important, fundamental data for policy making and legislation, registry implementation and the diagnosis, treatment and prevention of CKD in China.

Value of electron microscopy in the pathological diagnosis of native kidney biopsies in children.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Efficacy and safety of steroid combined with immunosuppressants in the treatment of primary IgA nephropathy in children: a Meta analysis].

OBJECTIVE: To systematically evaluate the efficacy and safety of steroid combined with immunosuppressants in the treatment of primary IgA nephropathy in children. METHODS: English and Chinese electronic databases were searched to include the studies on the efficacy and safety of steroid combined with immunosuppressants versus steroid alone in the treatment of primary IgA nephropathy in children. Outcome measures included proteinuria remission rate, urinary protein quantification, incidence of adverse events, estimated glomerular filtration rate, and incidence of renal dysfunction. Review Manager 5.3 software was used for data analysis. RESULTS: A total of 7 studies with 381 children were included. The children had moderate to severe proteinuria. The Meta analysis showed that compared with the steroid alone group, the steroid combined with immunosuppressants group achieved a significantly higher rate of proteinuria remission (RR=1.36, 95%CI: 1.19-1.55, P<0.001) and significantly lower urinary protein quantification (SMD=-0.82, 95%CI: -1.23 to -0.41, P<0.001). There was no significant difference in the incidence rate of adverse events between the two groups (RR=1.28, 95%CI: 0.92-1.77, P=0.14). CONCLUSIONS: The current evidence shows that for children with primary IgA nephropathy who have moderate to severe proteinuria, steroid combined with immunosuppressants has a better effect than steroid alone and does not increase the incidence rate of adverse events.

The Physical Vapor Transport Method for Bulk AlN Crystal Growth.

In this report, the development of physical vapor transport (PVT) methods for bulk aluminum nitride (AlN) crystal growth is reviewed. Three modified PVT methods with different features including selected growth at a conical zone, freestanding growth on a perforated sheet, and nucleation control with an inverse temperature gradient are discussed and compared in terms of the size and quality of the bulk AlN crystals they can produce as well as the process complexity. The PVT method with an inverse temperature gradient is able to significantly reduce the nucleation rate and realize the dominant growth of only one bulk AlN single crystal, and thus grow centimeter-sized bulk AlN single crystals. X-ray rocking curve (XRC) and Raman spectroscopy measurements showed a high crystalline quality of the prepared AlN crystals. The inverse temperature gradient provides an efficient and relatively low-cost method for the preparation of large-sized and high-quality AlN seed crystals used for seeded growth, devoted to the diameter enlargement and quality improvement of bulk AlN single crystals.

What is the impact of human leukocyte antigen mismatching on graft survival and mortality in renal transplantation? A meta-analysis of 23 cohort studies involving 486,608 recipients.

BACKGROUND: The magnitude effects of human leukocyte antigen (HLA) mismatching on post-transplant outcomes of kidney transplantation remain controversial. We aim to quantitatively assess the associations of HLA mismatching with graft survival and mortality in adult kidney transplantation. METHODS: We searched PubMed, EMBASE and the Cochrane Library from their inception to December, 2016. Priori clinical outcomes were overall graft failure, death-censored graft failure and all-cause mortality. RESULTS: A total of 23 cohort studies covering 486,608 recipients were selected. HLA per mismatch was significant associated with increased risks of overall graft failure (hazard ratio (HR), 1.06; 95% confidence interval (CI), 1.05-1.07), death-censored graft failure (HR: 1.09; 95% CI 1.06-1.12) and all-cause mortality (HR: 1.04; 95% CI: 1.02-1.07). Besides, HLA-DR mismatches were significant associated with worse overall graft survival (HR: 1.12, 95% CI: 1.05-1.21). For HLA-A locus, the association was insignificant (HR: 1.06; 95% CI: 0.98-1.14). We observed no significant association between HLA-B locus and overall graft failure (HR: 1.01; 95% CI: 0.90-1.15). In subgroup analyses, we found recipient sample size and ethnicity maybe the potential sources of heterogeneity. CONCLUSIONS: HLA mismatching was still a critical prognostic factor that affects graft and recipient survival. HLA-DR mismatching has a substantial impact on recipient's graft survival. HLA-A mismatching has minor but insignificant impact on graft survival outcomes.

Effect of human leukocyte antigen mismatching on the outcomes of pediatric kidney transplantation: a systematic review and meta-analysis.

BACKGROUND: Kidney transplantation is regarded as the optimal treatment for pediatric patients with end-stage renal disease. Here, we address a controversial topic in pediatric kidney transplantation by performing a quantitative evaluation of the effect of human leukocyte antigen (HLA) mismatching on the outcomes of pediatric kidney transplantation. METHODS: We systematically searched PubMed, EMBASE and the Cochrane Library from their inception to 31 December 2016 for cohort studies assessing the risk ratio (RR) of HLA mismatching on pediatric kidney transplantation. Outcome measures included graft failure, rejection and all-cause mortality. RRs and 95% confidence intervals (CIs) were used as estimates of effect size in random-effect models. RESULTS: Eighteen studies comprising a total of 26 018 pediatric recipients were included in the evaluation. Compared with 0-1 HLA-DR mismatch, 2 mismatches significantly increased the risk of graft failure at 1 year (RR: 1.41, 95% CI: 1.11-1.80), 3 years (RR: 1.28, 95% CI: 1.08-1.52), 5 years (RR: 1.21, 95% CI: 1.04-1.41) and 10 years (RR: 1.30, 95% CI: 1.02-1.67). For HLA-A + B, the 5-year graft failure risk was higher for 2-4 mismatches compared with 0-1 mismatch (RR: 3.17, 95% CI: 1.20-8.36), but not for 3-4 compared with 0-2 mismatches (RR: 1.49, 95% CI: 0.79-2.80). CONCLUSIONS: Based on pooled analysis, HLA-DR and HLA-A + B are important factors affecting post-transplant outcomes, especially graft failure, in pediatric recipients. Additional randomized controlled trials with higher quality evidence are needed for further investigation.

Long-term treatment by ACE inhibitors and angiotensin receptor blockers in children with Alport syndrome.

BACKGROUND: 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). METHODS: This was a respective review of 79 Chinese children with AS who received ACEi alone or combined ACEi + ARB therapy. RESULTS: 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, <25, 25-50, and ≥50 mg/kg/day, respectively; after 1 year of treatment the proteinuria had decreased from 11.0 to 9.7 mg/kg/day, from 34.6 to 15.2 mg/kg/day, and from 73.0 to 50.0 mg/kg/day in each group, respectively. Proteinuria decreased significantly during the first 2 years of treatment and was stable from the third to fifth years of treatment. There was no statistically significant difference in the antiproteinuric effect of the ACEi and ACEi + ARB treatments in patients with severe or less severe mutations after 1 year of therapy. Five children stopped the ACEi + ARB treatment due to a decline in creatinine clearance. CONCLUSION: Our findings demonstrate that early and long-term ACEi and ARB treatments in children with AS is efficient and well tolerated. The antiproteinuric effect of ACEi and ARB is of equal value in children with severe and less severe mutations in the COL4An gene.

[Comparison of phenotypic features between patients with X-linked and autosomal recessive Alport syndrome].

OBJECTIVE: To further improve the recognition of Alport syndrome. METHODS: The patients with COL4A3, COL4A4 or COL4A5 mutations, admitted to Department of Pediatric, Peking University First Hospital from 2005 to 2009, were retrospectively studied. Their clinical and ultrastructural characteristics were compared between the male patients with X-linked dominant inheritance Alport syndrome (XLAS) and the patients with autosomal recessive inheritance Alport syndrome (ARAS). RESULTS: There were 54 male patients with XLAS and 14 patients with ARAS. Compared with the male patients with XLAS, episodic gross hematuria was prominent (P<0.001) in patients with ARAS. Family history was also different between the two groups (P=0.016). However, there was no significant difference in the age of identification of symptoms, initial manifestations, levels of proteinuria, extrarenal signs and ultra-structural glomerular basement membrane changes between the two groups. CONCLUSION: There are some features that distinguish between the patients with XLAS and the patients with ARAS.

Histologic and Clinical Factors Associated with Kidney Outcomes in IgA Vasculitis Nephritis.

BACKGROUND: Nephritis is a common manifestation of IgA vasculitis and is morphologically indistinguishable from IgA nephropathy. While MEST-C scores are predictive of kidney outcomes in IgA nephropathy, their value in IgA vasculitis nephritis has not been investigated in large multiethnic cohorts. METHODS: Biopsies from 262 children and 99 adults with IgA vasculitis nephritis ( N =361) from 23 centers in North America, Europe, and Asia were independently scored by three pathologists. MEST-C scores were assessed for correlation with eGFR/proteinuria at biopsy. Because most patients ( N =309, 86%) received immunosuppression, risk factors for outcomes were evaluated in this group using latent class mixed models to identify classes of eGFR trajectories over a median follow-up of 2.7 years (interquartile range, 1.2-5.1). Clinical and histologic parameters associated with each class were determined using logistic regression. RESULTS: M, E, T, and C scores were correlated with either eGFR or proteinuria at biopsy. Two classes were identified by latent class mixed model, one with initial improvement in eGFR followed by a late decline (class 1, N =91) and another with stable eGFR (class 2, N =218). Class 1 was associated with a higher risk of an established kidney outcome (time to ≥30% decline in eGFR or kidney failure; hazard ratio, 5.84; 95% confidence interval, 2.37 to 14.4). Among MEST-C scores, only E1 was associated with class 1 by multivariable analysis. Other factors associated with class 1 were age 18 years and younger, male sex, lower eGFR at biopsy, and extrarenal noncutaneous disease. Fibrous crescents without active changes were associated with class 2. CONCLUSIONS: Kidney outcome in patients with biopsied IgA vasculitis nephritis treated with immunosuppression was determined by clinical risk factors and endocapillary hypercellularity (E1) and fibrous crescents, which are features that are not part of the International Study of Diseases of Children classification.

Integration of artificial intelligence and multi-omics in kidney diseases.

Kidney disease is a leading cause of death worldwide. Currently, the diagnosis of kidney diseases and the grading of their severity are mainly based on clinical features, which do not reveal the underlying molecular pathways. More recent surge of ∼omics studies has greatly catalyzed disease research. The advent of artificial intelligence (AI) has opened the avenue for the efficient integration and interpretation of big datasets for discovering clinically actionable knowledge. This review discusses how AI and multi-omics can be applied and integrated, to offer opportunities to develop novel diagnostic and therapeutic means in kidney diseases. The combination of new technology and novel analysis pipelines can lead to breakthroughs in expanding our understanding of disease pathogenesis, shedding new light on biomarkers and disease classification, as well as providing possibilities of precise treatment.