Pediatric Glomerular Disease Research Articles

#1927 Efficacy and safety of ripertamab in paediatic glomerular disease

Abstract Background and Aims Anti-B-cell treatment has been shown to be an efficient tactic for glomerular disease. Ripertamab as a novel anti-CD20 monoclonal antibody developed by China, has been structurally optimized to specifically bind to the transmembrane antigen CD20, with an amino acid difference in the constant region sequence compared to rituximab. This study reports the efficacy and safety of ripertamab in children with different glomerular diseases. Method We retrospectively report the data of 140 children with a diagnosis of glomerular disease and a treatment with ripertamab in a single center Results A total of 140 children (age, 11.2 ± 3.7 years; 58.6% boys) were included, 69/140 (49.3%) steroid-dependent nephrotic syndrome (SDNS), 38/140 (27.1%) steroid-resistant but CNIs-dependent nephrotic syndrome, 18/140 (12.9%) Lupus nephritis, 5/140 (3.6%) atypical hemolytic uremic syndrome, 4/140 (2.9%) ANCA associated vasculitis, 3/140 (2.1%) membranous nephropathy and 3/140 (2.1%) IgA vasculitis nephritis. The Median (IQR) duration of disease before the application of ripertamab was 4.4 (2.3, 7.4) years. They totally received 200 courses of ripertamab. A total of 83, 55, 1, and 1 patient received one, two, three, and four courses, respectively. Ripertamab 375 mg/m2 (maximum 500 mg) were injected per course. B cell depletion could be observed in 129/140 (92.1%) children one month after ripertamab. An additional course was administered due to recovery of B-cells or relapse. Median (IQR) follow-up was 0.8 (0.5, 1.1) years. The median relapse-free period after the first course was 4.7 months (IQR, 3.8, 5.6 months). Most of the relapses developed simultaneously with recovery of B-cells. About 36.7% of these children stopped steroid during the follow-up. One or more immunosuppressant (IS) drugs needed before ripertamab infusion could be withdrawn or reduced in 109/140 patients (77.9%). None of the patients developed life-threatening adverse events. Conclusion This study suggests that ripertamab could be an effective and safe treatment for various pediatric glomerular diseases.

Diagnostic Challenges and Emerging Pathogeneses of Selected Glomerulopathies.

Recent progress in glomerular immune complex and complement-mediated diseases have refined diagnostic categories and informed mechanistic understanding of disease development in pediatric patients. Herein, we discuss selected advances in 3 categories. First, membranous nephropathy antigens are increasingly utilized to characterize disease in pediatric patients and include phospholipase A2 receptor (PLA2R), Semaphorin 3B (Sema3B), neural epidermal growth factor-like 1 (NELL1), and protocadherin FAT1, as well as the lupus membranous-associated antigens exostosin 1/2 (EXT1/2), neural cell adhesion molecule 1 (NCAM1), and transforming growth factor beta receptor 3 (TGFBR3). Second, we examine advances in techniques for paraffin and light chain immunofluorescence (IF), including the former's function as a salvage technique and their necessity for diagnosis in adolescent cases of membranous-like glomerulopathy with masked IgG kappa deposits (MGMID) and proliferative glomerulonephritis with monotypic Ig deposits (PGNMID), respectively. Finally, progress in understanding the roles of complement in pediatric glomerular disease is reviewed, with specific attention to overlapping clinical, histologic, and genetic or functional alternative complement pathway (AP) abnormalities among C3 glomerulopathy (C3G), infection-related and post-infectious GN, "atypical" post-infectious GN, immune complex mediated membranoproliferative glomerulonephritis (IC-MPGN), and atypical hemolytic uremic syndrome (aHUS).

Characterization of glomerular basement membrane components within pediatric glomerular diseases.

Disruptions in gene expression associated with the glomerular basement membrane (GBM) could precipitate glomerular dysfunction. Nevertheless, a comprehensive understanding of the characterization of GBM components within pediatric glomerular diseases and their potential association with glomerular function necessitates further systematic investigation. We conducted a systematic analysis focusing on the pathological transformations and molecular attributes of key constituents within the GBM, specifically Collagen IV α3α4α5, Laminin α5β2γ1, and Integrin α3β1, across prevalent pediatric glomerular diseases. We observed upregulation of linear expression levels of COL4A3/4/5 and Laminin 5α proteins, along with a partial reduction in the linear structural expression of Podocin in idiopathic nephrotic syndrome (INS), encompassing minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS), but showing a reduction in IgA nephropathy (IgAN), IgA vasculitis nephritis (IgAVN) and lupus nephritis (LN). Furthermore, our study revealed reductions in Laminin β2γ1 and Integrin α3β1 in both primary and secondary childhood glomerular diseases. In INS, notably MCD and FSGS, there is a notable increase in the linear expression levels of COL4A3/4/5 and Laminin 5α proteins. In contrast, in IgAN, IgAVN, and LN, there is a consistent reduction in the expression of these markers. Furthermore, the persistent reduction of Laminin β2γ1 and Integrin α3β1 in both primary and secondary childhood glomerular diseases suggests a shared characteristic of structural alterations within the GBM across these conditions.

Diagnostic performance of renal cortical elasticity by supersonic shear wave imaging in pediatric glomerular disease

PurposeTo explore the diagnostic performance of renal cortical elasticity expressed by Young’s modulus (YM) using the supersonic shear wave imaging (SSI) technique in pediatric glomerular disease. Materials and methodsSeventy-one children with glomerular disease confirmed by renal biopsy and sixty healthy volunteers were enrolled in this study. Conventional and SSI ultrasound examinations were performed in all individuals for both kidneys. We measured renal length, renal width, renal thickness, parenchyma thickness, interlobar arterial resistive index (RI) and the YM of the middle and lower pole. ResultsRegardless of which pole and which side of the kidney, the YM in the disease group was significantly higher than that in the control group (P < 0.001). The YM of the middle pole in the left kidney demonstrated the largest AUC (0.936, P < 0.001), and the corresponding cut-off value was 15.48 kPa with a sensitivity of 87.3% and a specificity of 86.7%. There was no significant difference in the YM among different pathological types of pediatric glomerular disease in the disease group, and the same in different grades of patients with Immunoglobulin A (IgA) nephropathy by Lee classification and the Oxford Classification as well as Henoch-Schonlein purpura nephritis (HSPN) by International Study of Kidney Disease in Children (ISKDC) classification (P > 0.05). We found positive but weak correlations between the YM and renal length (r = 0.299, P = 0.001), renal width (r = 0.408, P < 0.001), renal thickness (r = 0.299, P = 0.001), and parenchyma thickness (r = 0.212, P = 0.015), whereas the YM had no significant correlations with age, sex, BMI, interlobar arterial RI, and laboratory findings (P > 0.05). ConclusionsSSI technology is a non-invasive and feasible method for the diagnosis of pediatric glomerular disease. However, SSI did not show good performance in distinguishing different pathological types and disease grades in our study.

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.

The expression of respiratory tract virus in pediatric glomerular disease: a retrospective study of 45 renal biopsy in China

BackgroundMore attention has been put on the relationship between pediatric glomerular disease and respiratory tract virus infection. Children with glomerular illness, however, are uncommonly found to have biopsy-proven pathological evidence of viral infection. The purpose of this study is to determine whether and what kind of respiratory viruses are found in renal biopsy from glomerular disorders.MethodsWe used a multiplex PCR to identify a wide range of respiratory tract viruses in the renal biopsy samples (n = 45) from children with glomerular disorders and a specific PCR to verify their expression.ResultsThese case series included 45 of 47 renal biopsy specimens, with 37.8% of male and 62.2% of female patients. Indications for a kidney biopsy were present in all of the individuals. In 80% of the samples, respiratory syncytial virus was discovered. Following that, the RSV subtypes in several pediatric renal disorders were found. There were 16 RSVA positives, 5 RSVB positives, and 15 RSVA/B positives, accounting for 44.4%, 13.9%, and 41.7%, respectively. Nephrotic syndrome samples made up 62.5% of RSVA positive specimens. The RSVA/B-positive was detected in all pathological histological types.ConclusionsPatients with glomerular disease exhibit respiratory tract viral expression in the renal tissues, especially respiratory syncytial virus. This research offers new information on the detection of respiratory tract viruses in renal tissue, which may facilitate the identification and treatment of pediatric glomerular diseases.

Pediatric Glomerular Diseases in North India-Epidemiology and Clinicopathologic Correlation.

Glomerular diseases vary with age, and it is important to investigate the spectrum of glomerular diseases in pediatric patients to help in a more precise clinical diagnosis and optimize the management of patients. We aimed to study the clinicopathologic pattern of pediatric glomerular diseases in North India. This is a 5-year retrospective, single-center cohort study. The database was searched to identify all pediatric patients with glomerular diseases in their native kidney biopsies. About 2890 native renal biopsies were studied, of which 409 were pediatric glomerular diseases. The median age was 15 years with a male preponderance. Nephrotic syndrome was the most common presentation (60.8%), followed by non-nephrotic proteinuria with hematuria (18.5%), rapidly proliferative glomerulonephritis (7%), isolated hematuria (5.3%), acute nephritic syndrome (3.4%), non-nephrotic proteinuria (1.9%), and advanced renal failure (0.7%). Minimal change disease (MCD) was the most common histological diagnosis, followed by focal segmental glomerulosclerosis (17.4%), IgA nephropathy (IgAN; 10%), membranous nephropathy (6.6%), lupus nephritis (5.9%), crescentic glomerulonephritis (2.9%), and C3 glomerulopathy (2.9%). Diffuse proliferative glomerulonephritis (DPGN) was the most common histological diagnosis in patients with hematuria and non-nephrotic as well as nephrotic range proteinuria. The most common histological diagnoses for isolated hematuria and acute nephritic syndrome were IgAN and postinfectious glomerulonephritis (PIGN), respectively. MCD and lupus nephritis are the most common pediatric primary and secondary histopathologic diagnoses, respectively. The adolescent-onset glomerular diseases have a higher frequency of IgAN, membranous nephropathy, and DPGN. PIGN is still an important differential in our pediatric patients presenting with acute nephritic syndrome.

The pathological spectrum of pediatric kidney disease: 18-Year experience from a single tertiary care center in northern Taiwan.

Glomerular disease is one of the leading causes of chronic kidney disease in children worldwide. Recent studies outlined the changing spectrum of glomerular disease in certain countries. Therefore, our study aimed to evaluate the histopathological patterns and changes in pediatric kidney disease over the past 18 years in northern Taiwan. This was a retrospective chart review study of pediatric patients (≤18 years of age) undergoing percutaneous renal biopsies (PRBs) of native kidneys between January 2002 and July 2020 from a Pediatric Care Center at Chang Gung Memorial Hospital, Taoyuan, Taiwan. This study analyzed a total of 339 pediatric native PRBs. The mean age of the subjects was 13.7±7.0 years (184 girls and 155 boys). The most common indications of PRBs included acute nephritic syndrome (55.7%), idiopathic nephrotic syndrome (22.7%), persistent asymptomatic hematuria (13.9%), and unexplained renal failure (7.7%). Our study revealed that proliferative lupus nephritis (LN), minimal change disease (MCD)-related nephrotic syndrome, and IgA nephropathy (IgAN) were the most frequent biopsy-proven pediatric glomerular diseases. In addition, we showed that severe acute post-streptococcal glomerulonephritis (APSGN) was infrequent and has not even been diagnosed since 2010. Our result revealed that the spectrum of biopsy-proven pediatric kidney disease has not changed significantly over the past two decades. Furthermore, proliferative LN, MCD, and primary IgAN continue to be the most common histopathological diagnoses among Taiwanese children.

How I Treat Steroid-Sensitive Nephrotic Syndrome in Children.

Steroid-sensitive nephrotic syndrome represents the most frequent pediatric glomerular disease ([1][1]), persisting into adulthood in approximately 30% of patients ([2][2]). Most frequently, steroid-sensitive nephrotic syndrome is not a severe condition, not leading to kidney failure and eventually

Epidemiology of biopsy-proven glomerular diseases in Chinese children: A scoping review.

Glomerular disease is the leading cause of chronic kidney disease globally. No scoping review reports have focused on China's spectrum of glomerular diseases in children. This study aimed to systematically identify and describe retrospective studies on pediatric glomerular disease based on available data on sex, age, study period, and region. Six databases were systematically searched for relevant studies from initiation to December 2021 in PubMed, Embase, Web of Science, Global Health Library, Wangfang Database, and CNKI. Thirty-four studies were identified in the scoping review, including 40,430 patients with biopsy-proven diagnoses. The proportion of boys was significantly higher than that of girls. In this study, 28,280 (70%) cases were primary glomerular disease, 10,547 (26.1%) cases were diagnosed as secondary glomerular disease, and 1146 (2.8%) cases were hereditary glomerular disease. Minimal change disease is the most common glomerular disease among children in China, followed by mesangial proliferative glomerulonephritis, IgA nephropathy, and purpura nephritis. We observed increments in glomerular diseases in periods 2 (2001-2010) and 3 (2011-2021). The proportion of major glomerular diseases varies significantly in the different regions of China. The spectrum of pediatric glomerular diseases varied across sex, age groups, study periods, and regions, and has changed considerably over the past 30 years.

Levamisole in steroid-dependent nephrotic syndrome in children: A case series

Nephrotic syndrome (NS) is a common clinical entity encountered in children and adults. Steriod Dependent Nephrotic Syndrome(SDNS) is one of the most common pediatric glomerular diseases. However, a significant chunk of cases follows a relapsing and remitting course. Various modalities such as cyclophosphamide, cyclosporine, tacrolimus, mycophenolate mofetil (MMF), levamisole, and rituximab have been tried in patients with steroid-dependent or frequently relapsing NS (FRNS). We describe our experience of using levamisole in nine patients with steroid-dependent NS. We used the regimen of levamisole dosing at 2.5 mg/kg on alternate days, along with alternate dosing of steroids at the lowest possible doses to achieve remission. During follow-up, two of the patients were switched over to a calcineurin inhibitor (tacrolimus). All the remaining seven patients responded to levamisole and attained remission. At 18 months follow-up, four patients were on a minimal dose of steroids (prednisolone 0.25 mg/kg alternate day) with levamisole 2.5 mg/kg, whereas three patients were on prednisolone 0.5 mg/kg/alternate day with levamisole 2.5 mg/kg alternate day. Among the patients with steroid-sensitive NS, 30%–60% are frequently relapsing or steroid-dependent forms of NS. Corticosteroids have well recognized and potentially serious adverse effects. A lot of steroid-sparing agents such as MMF, rituximab, alkylating agents like cyclophosphamide, and calcineurin inhibitors have been used in clinical medicine, to mitigate the above mentioned adverse effects of prolonged use of corticosteroids, with varying success. But these medications have significant side effects and toxicity profiles of their own. Our case series reiterates the role of levamisole in FRNS and SDNS patients without much risk of adverse events in patients and hence being a relatively less expensive treatment option.

2020 update on the renin-angiotensin-aldosterone system in pediatric kidney disease and its interactions with coronavirus.

The last decade was crucial for our understanding of the renin–angiotensin–aldosterone system (RAAS) as a two-axis, counter-regulatory system, divided into the classical axis, formed by angiotensin-converting enzyme (ACE), angiotensin II (Ang II), and the angiotensin type 1 receptor (AT1R), and the alternative axis comprising angiotensin-converting enzyme 2 (ACE2), angiotensin-(1-7) (Ang-(1-7)), and the Mas receptor. Breakthrough discoveries also took place, with other RAAS endopeptides being described, including alamandine and angiotensin A. In this review, we characterize the two RAAS axes and the role of their components in pediatric kidney diseases, including childhood hypertension (HTN), pediatric glomerular diseases, congenital abnormalities of the kidney and urinary tract (CAKUT), and chronic kidney disease (CKD). We also present recent findings on potential interactions between the novel coronavirus, SARS-CoV-2, and components of the RAAS, as well as potential implications of coronavirus disease 2019 (COVID-19) for pediatric kidney diseases.

Management of Canadian Pediatric Patients With Glomerular Diseases During the COVID-19 Pandemic: Recommendations From the Canadian Association of Pediatric Nephrologists COVID-19 Rapid Response Team.

Purpose:The goal of these recommendations is to provide guidance on the optimal care of children with glomerular diseases during the COVID-19 pandemic. Patients with glomerular diseases are known to be more susceptible to infection. Risk factors include decreased vaccine uptake, urinary loss of immunoglobulins, and treatment with immunosuppressive medications. The Canadian Society of Nephrology (CSN) recently published guidelines on the care of adult glomerulonephritis patients. This guideline aims to expand and adapt those recommendations for programs caring for children with glomerular diseases.Sources of information:We used the CSN COVID-19 Rapid Response Team adult glomerulonephritis recommendations, published in the Canadian Journal of Kidney Health and Disease, as the foundation for our guidelines. We reviewed documents published by nephrology and non-nephrology societies and health care agencies focused on kidney disease and immunocompromised populations. Finally, we conducted a formal literature review of publications relevant to pediatric and adult glomerular disease, chronic kidney disease, hypertension, and immunosuppression in the context of the COVID-19 pandemic.Methods:The leadership of the Canadian Association of Pediatric Nephrologists (CAPN), which is affiliated with the CSN, identified a team of clinicians and researchers with expertise in pediatric glomerular diseases. The aim was to adapt Canadian adult glomerulonephritis guidelines to make them applicable to children and discuss pediatric-specific considerations. The updated guidelines were peer-reviewed by senior clinicians with expertise in the care of childhood glomerular diseases.Key findings:We identified a number of key areas of glomerular disease care likely to be affected by the COVID-19 pandemic, including (1) clinic visit scheduling, (2) visit types, (3) provision of multidisciplinary care, (4) blood work and imaging, (5) home monitoring, (6) immunosuppression, (7) other medications, (8) immunizations, (9) management of children with suspected COVID-19, (10) renal biopsy, (11) patient education and support, and (12) school and child care.Limitations:There are minimal data regarding the characteristics and outcomes of COVID-19 in adult or pediatric glomerular disease patients, as well as the efficacy of strategies to prevent infection transmission within these populations. Therefore, the majority of these recommendations are based on expert opinion and consensus guidance. To expedite the publication of these guidelines, an internal peer-review process was conducted, which may not have been as rigorous as formal journal peer-review.Implications:These guidelines are intended to promote optimal care delivery for children with existing or newly diagnosed glomerular diseases during the COVID-19 pandemic. The implications of modified care delivery, altered immunosuppression strategies, and limited access to existing resources remain uncertain.

Using Electronic Health Record Data to Rapidly Identify Children with Glomerular Disease for Clinical Research.

The rarity of pediatric glomerular disease makes it difficult to identify sufficient numbers of participants for clinical trials. This leaves limited data to guide improvements in care for these patients. The authors developed and tested an electronic health record (EHR) algorithm to identify children with glomerular disease. We used EHR data from 231 patients with glomerular disorders at a single center to develop a computerized algorithm comprising diagnosis, kidney biopsy, and transplant procedure codes. The algorithm was tested using PEDSnet, a national network of eight children's hospitals with data on >6.5 million children. Patients with three or more nephrologist encounters (n=55,560) not meeting the computable phenotype definition of glomerular disease were defined as nonglomerular cases. A reviewer blinded to case status used a standardized form to review random samples of cases (n=800) and nonglomerular cases (n=798). The final algorithm consisted of two or more diagnosis codes from a qualifying list or one diagnosis code and a pretransplant biopsy. Performance characteristics among the population with three or more nephrology encounters were sensitivity, 96% (95% CI, 94% to 97%); specificity, 93% (95% CI, 91% to 94%); positive predictive value (PPV), 89% (95% CI, 86% to 91%); negative predictive value, 97% (95% CI, 96% to 98%); and area under the receiver operating characteristics curve, 94% (95% CI, 93% to 95%). Requiring that the sum of nephrotic syndrome diagnosis codes exceed that of glomerulonephritis codes identified children with nephrotic syndrome or biopsy-based minimal change nephropathy, FSGS, or membranous nephropathy, with 94% sensitivity and 92% PPV. The algorithm identified 6657 children with glomerular disease across PEDSnet, ≥50% of whom were seen within 18 months. The authors developed an EHR-based algorithm and demonstrated that it had excellent classification accuracy across PEDSnet. This tool may enable faster identification of cohorts of pediatric patients with glomerular disease for observational or prospective studies.

Levamisole in Children with Idiopathic Nephrotic Syndrome: Clinical Efficacy and Pathophysiological Aspects.

Steroid sensitive nephrotic syndrome is one of the most common pediatric glomerular diseases. Unfortunately, it follows a relapsing and remitting course in the majority of cases, with 50% of all cases relapsing once or even more often. Most children with idiopathic nephrotic syndrome respond initially to steroid therapy, nevertheless repeated courses for patients with relapses induce significant steroid toxicity. Patients with frequent relapses or steroid dependency thus require alternative treatment, such as cyclophosphamide, cyclosporine, tacrolimus, mycophenolate mofetil, levamisole, or rituximab. To reduce the relapse rate, several drugs have been used. Among these, levamisole has been considered the least toxic and least expensive therapy. Several randomized controlled trials (RCT) showed that levamisole is effective in reducing the relapse risk in steroid sensitive forms of nephrotic syndrome with a low frequency of side effects. Levamisole is a synthetic imidazothiazole derivative with immune-modulatory properties. In this article, we review recent data from randomized trials and observational studies to assess the efficacy of levamisole in frequently relapsing nephrotic syndrome and steroid-dependent nephrotic syndrome.

Contribution of Electron Microscopy to the Clinicopathologic Diagnosis in Childhood Glomerular Renal Diseases

Background: Electron microscopy (EM) provides another diagnostic assessment of glomerular lesions in addition to light and fluorescent microscopy. Objectives: We evaluated the contribution of diagnostic EM in childhood glomerular diseases. Patients and methods: Forty-eight renal biopsies which were assessed by EM between 2000 and 2014 were evaluated. Results: There were 21 (44%) females and 27 (56%) males, ages ranged between 6 and 204 months. EM findings were compatible with light and immunofluorescence microscopy in 65%, made additional contributions to diagnosis in 31% (especially in focal segmental glomerulosclerosis, Alport disease, membranoproliferative glomerulonephritis, dense deposit disease, thin basement membrane disease, and nephronophthisis), and was non-contributory in 4%. Conclusion: Electron microscopic evaluation supports other histopathological diagnoses in most cases, contributes additional diagnostic information in pediatric glomerular disease, especially in FSGS, thin glomerular basement membrane nephropathy, Alport disease, MPGN, and dense deposit disease, and its utilization should clinically justify the increase in cost and testing time.

Incidence of pediatric glomerular diseases in Arab world: A systematic review

Despite the high number of Arab children, there are a scanty available data about different types of pediatric glomerular diseases in all Arab countries. Very few Arab countries have a national renal biopsy registry. In this review, we performed a systematic review analyzing the incidence of pediatric glomerular disease in all Arab countries. Relevant manuscripts in all 22 Arab countries found through searches of Medline, Science Direct, Embase and Google Scholar were evaluated. The period was from January 1990 to March 2018. A total of 17 manuscripts containing 3083 renal biopsies from seven countries were analyzed. Male-to-female ratio was 1.3:1. Saudi Arabia revealed the most published studies with seven papers. The average period of the study was 8.63 years. Retrospective studies represent 94.12%. Minimal change disease (MCD) (29.25%), focal and segmental glomerulosclerosis (FSGS) (22.34%), mesangioproliferative glomerulonephritis (14.78%), membranoproliferative glomerulonephritis (6.9%), IgA nephropathy (3.98%), and membranous glomerulopathy (2.65%) were the top types of primary glomerular diseases. The most common types of secondary glomerular diseases were lupus nephritis (36.1%), postinfectious glomerulonephritis (17.62%), congenital nephrotic syndrome (6.08%), Alport syndrome (4.71%), Henoch-Schönlein purpura (1.49%), and amyloidosis (1.36%). In conclusion, MCD and lupus nephritis are, respectively, the most common types of primary and secondary glomerular diseases in children of all evaluated Arab countries. FSGS is the predominant pattern of primary glomerular diseases in Asian Arab countries. The trend of all types of glomerular diseases has not changed in the past 28 years except a noted significant reduction in FSGS. Arab countries are strongly recommended to establish a renal biopsy registry.

Significance of glomerular fibrinogen deposition in children with Henoch-Sch\xf6nlein purpura nephritis

BackgroundHenoch-Schönlein purpura nephritis (HSPN) is the most common pediatric secondary glomerular disease. This study aimed to investigate the significance of glomerular fibrinogen (Fib) deposition in children with HSPN.MethodsEighty-two patients with HSPN were enrolled retrospectively at the Children’s Hospital of Soochow University from January 2015 to March 2017. Patients were divided into groups according to the presence or absence and intensity of glomerular Fib deposits, and clinical and pathological features were compared among the groups.ResultsGlomerular Fib deposition was observed in 64 children (78.05%), including 1 Fib± case (1.22%), 23 Fib+ cases (28.05%), 37 Fib++ cases (45.12%), and 3 Fib+++ cases (3.66%). Significantly different levels of high-sensitivity C-reactive protein (hs-CRP), D-dimer (DD), proportions of CD19 + CD23+ cells and urine microalbumin:creatinine ratios (UMA/Cr) were noted among the different Fib deposition groups (no, mild and severe). Pairwise comparison in multiple groups revealed significantly increased hs-CRP, proportion of CD19 + CD23+ cells and UMA/Cr in the severe deposition group compared with the mild and no deposition groups, and remarkably increased DD levels were noted in the severe and mild deposition groups compared with the no deposition group. The degree of glomerular Fib deposition was positively correlated with the degree of glomerular IgA deposition, and the incidence of glomerular IgG deposition in the severe deposition group was increased compared with the no deposition group.ConclusionHSPN children with glomerular Fib deposition, especially those with severe Fib deposition, exhibit more severely disordered immunologic function, inflammatory reactions and hypercoagulability; glomerular damage in these patients may also be more severe.

The Spectrum of Biopsy-Proven Glomerular Diseases among Children in China: A National, Cross-Sectional Survey.

High-quality epidemiologic data on the spectrum of biopsy-proven glomerular diseases among children are limited. This study aimed to determine the profile of and temporal change in biopsy-proven pediatric glomerular diseases in China. We previously conducted a nationwide kidney biopsy survey including 71,151 patients over an 11-year period from January 2004 to December 2014. A total of 7962 children younger than 18 years old from 115 hospitals across China with biopsy-proven glomerular diseases were included in this study. The demographic and clinical variables were extracted from referral records and pathology reports. The composition of pediatric glomerular diseases and clinicopathologic correlations in different sexes, age groups, and regions were assessed. The changing patterns of common glomerulopathies over the study period were examined. Nephrotic syndrome (50%) was the most frequent indication for kidney biopsy in children. Minimal change disease was the most common primary glomerular disease (29%) followed by IgA nephropathy (17%). Henoch-Schonlein purpura nephritis (13%) and lupus nephritis (9%) were the most common secondary glomerular diseases. The proportion of minimal change disease was significant higher in boys (38%) than in girls (13%), whereas lupus nephritis was more prevalent in girls (20%) than in boys (3%). Purpura nephritis (23%) was the major pathologic pattern in younger children (0-12 years old), whereas minimal change disease (33%) was the most common glomerulopathy in adolescents (13-18 years old). The clinicopathologic correlations were slightly different between sexes and age groups. We observed increases in the proportions of minimal change disease, purpura nephritis, and membranous nephropathy over the study period that were contemporaneous with a fall in the proportion of FSGS. The spectrum of glomerular diseases among children varied across sexes, age groups, and regions and changed substantially from 2004 to 2014 in China.

Glomerular Diseases in Children.

Unique challenges exist in the diagnosis and treatment of glomerular diseases with their onset during childhood. Mounting evidence supports the notion that earlier onset cases occur due to larger numbers of genetic risk alleles. Nearly all causes of adult-onset glomerulonephritis, nephrotic syndrome, and thrombotic microangiopathy have also been described in children, although the prevalence of specific causes differs. Postinfectious glomerulonephritis, Henoch-Schönlein purpura nephritis, and minimal change disease remain the most common causes of glomerular disease in younger children in the United States and can be diagnosed clinically without need for biopsy. IgA nephropathy is the most common pediatric glomerular disease diagnosed by kidney biopsy and is considered the most common chronic glomerulopathy worldwide. In both developing and developed countries, there is a strong relationship between infectious diseases and nephritis onset or relapse. Although research has led to a better understanding of how to classify and manage glomerular diseases in children, the need for disease-specific biomarkers of activity and chronicity remains a hurdle. The strength of the immune system and the growth and maturation that occurs during adolescence are unique and require age-specific approaches to disease management.