[Early identification of acute kidney injury in children with primary nephrotic syndrome]. / å„¿ç«¥åŽŸå‘æ€§è‚¾ç— ç»¼åˆå¾å¹¶å‘æ€¥æ€§è‚¾æŸä¼¤çš„æ—©æœŸè¯†åˆ«.

OBJECTIVES: To investigate the incidence and risk factors for acute kidney injury (AKI) in children with primary nephrotic syndrome (PNS), as well as the role of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) in the early identification of AKI in these children. METHODS: A prospective collection of clinical data from children hospitalized with PNS at the Children's Hospital of the Capital Institute of Pediatrics from January 2021 to October 2022 was conducted. The children were divided into two groups based on the presence of AKI: the AKI group (47 cases) and the non-AKI group (169 cases). The risk factors for AKI in children with PNS were identified by multivariate logistic regression analysis. Urinary KIM-1 and NGAL levels were compared between the AKI and non-AKI groups, as well as among the different stages of AKI. RESULTS: The incidence of AKI in children with PNS was 21.8%. Multivariate logistic regression analysis revealed that steroid-resistant nephrotic syndrome, gastrointestinal infections, and heavy proteinuria were independent risk factors for AKI in these children with PNS (P<0.05). Urinary KIM-1 and NGAL levels were higher in the AKI group compared to the non-AKI group (P<0.05), and the urinary NGAL and KIM-1 levels in the AKI stage 2 and stage 3 subgroups were higher than those in the AKI stage 1 subgroup (P<0.017). CONCLUSIONS: KIM-1 and NGAL can serve as biomarkers for the early diagnosis of AKI in children with PNS. Identifying high-risk populations for AKI in children with PNS and strengthening the monitoring of related risk factors is of significant importance.

Spectrum of Alport syndrome in an Indian cohort.

BACKGROUND: Next-generation sequencing has enabled non-invasive diagnosis of type IV collagen disease in clinical settings other than the typical presentation of Alport syndrome (AS). METHODS: We reviewed the clinical and histological records of children diagnosed with Alport syndrome based on next-generation sequencing. Variants on clinical exome sequencing were categorized using ACMG 2015 criteria. RESULTS: During 2015-2023, we found 43 patients (34 boys) with 39 variants in COL4A5 (n = 27), COL4A4 (n = 7), and COL4A3 (n = 5). Thirty, 8, and 5 patients had X-linked, autosomal recessive, and autosomal dominant disease, respectively. The median (IQR) age and eGFR at diagnosis were 10 (7-13) years and 100.1 (59-140) ml/min/1.73 m2, respectively. Fifteen patients were initially diagnosed with steroid-resistant nephrotic syndrome. Alport syndrome was suspected in these patients due to persistent microscopic hematuria, eGFR < 90 ml/min/1.73 m2, characteristic histology, and/or non-response to immunosuppression. Of 26 patients who underwent kidney biopsy, light microscopy revealed focal segmental glomerulosclerosis, minimal change disease, and mesangial proliferative glomerulonephritis in 9, 9, and 8 patients, respectively. Electron microscopy (n = 18) showed characteristic glomerular basement membrane changes and/or foot process effacement in 12 and 16 cases, respectively. Twenty-one patients (48.8%) had high-frequency sensorineural hearing loss, while two had lenticonus. Twelve patients progressed to chronic kidney disease stages 4-5. Median survival (IQR) with eGFR > 30 ml/min/1.73 m2 was 15.6 (13-18) years. CONCLUSIONS: The phenotype of Alport syndrome varies from asymptomatic urinary abnormalities to hematuria, proteinuria and/or low eGFR, and steroid-resistant nephrotic syndrome. Adverse outcomes are common, especially in boys with X-linked disease.

Efficacy and safety of oral cyclophosphamide versus mycophenolate mofetil in childhood nephrotic syndrome: an open-label comparative study.

INTRODUCTION: There is a scarcity of research comparing the efficacy of cyclophosphamide and mycophenolate mofetil in childhood nephrotic syndrome. The aim was to evaluate the efficacy and safety of oral cyclophosphamide (CYC) and mycophenolate mofetil (MMF) in children with steroid-sensitive nephrotic syndrome in terms of the proportion of children who have been off steroids for at least 6 months without proteinuria (responders). METHODS: This open-label retrospective-prospective comparative study was conducted in a pediatric nephrology clinic of a referral center for children between 1 and 18 years of age with FR/SD nephrotic syndrome. Group A consisted of patients who received oral cyclophosphamide (100, 25% female) at a dose of 2-2.5 mg/kg once daily for a period of 8-12 weeks. Group B consisted of patients who received oral mycophenolate mofetil (n = 61, 18% female) (dose: 800-1200 mg/m2) for at least 12 months. Responders were defined as children who were off steroids for at least 6 months along with absence of proteinuria. RESULTS: In the CYC group, 50% of the patients were responders, whereas 54% of the patients in the MMF group were responders (p = 0.614). The time to first relapse with CYC was 7 months (IQR 5.25-11) compared to 7 months (IQR 3.5-12) with MMF (p = 0.092). The relapse rate in the CYC group was 1.77 relapses per patient-year compared to 1.295 relapses per patient-year in the MMF group. The difference in relapse rate was significant (-0.474; 95% CI, 0.09 to 0.86 relapses/person-year) (p value = 0.009). Multivariate analysis revealed that an age of less than 5 years at the start of treatment was a significant factor for a better response to MMF (p value = 0.039, OR = 2.988, CI -1.055-8.468). CONCLUSIONS: The efficacy of MMF was similar to that of CYC in terms of response (6 months without steroids) in children with FR/SD nephrotic syndrome. MMF showed a favorable response in terms of the frequency of relapse and treatment failure. REGISTRATION OF THE STUDY WITH CLINICAL TRIALS REGISTRY OF INDIA: ( http://ctri.nic.in ;CTRI/2021/06/034421) (Dt: 28/06/2021).

Polymyalgia Rheumatica Complicated by Nephrotic Syndrome in a Nonagenarian: A Case Report.

This case report describes a 91-year-old bedridden man with a complex medical history who presented with fever and low oxygen saturation, suspected to be aspiration pneumonia. Further investigation revealed nephrotic syndrome, microscopic hematuria, and joint pain. The diagnosis of polymyalgia rheumatica (PMR) was considered due to the presence of characteristic symptoms and elevated inflammatory markers despite the inability to perform a kidney biopsy. The patient was treated with low-dose prednisolone (PSL), leading to significant improvement in joint pain, renal function, and overall condition. This case highlights the importance of considering PMR in elderly patients with unexplained nephrotic syndrome and systemic inflammation. Early diagnosis and corticosteroid treatment can improve clinical outcomes and enhance activities of daily living. This report underscores the need for awareness of PMR as a potential cause of nephrotic syndrome in the elderly and the effectiveness of PSL in managing such cases.

Pregnancy occurring in AA amyloidosis: a series of 27 patients including 3 new French cases.

BACKGROUND: AA amyloidosis (AAA) is a multisystem disease related to the deposition in tissues of serum amyloid A protein which complicates chronic inflammation. It is a potentially fatal complication.  Renal involvement is the most common manifestation of AAA. Pregnancy in women with chronic kidney disease  is considered to be at risk for specific pregnancy complications and the worsening of their underlying renal dysfunction. Our aim was to report pregnancy in our AAA patients and discuss the outcome through a literature review. METHODS: French cases were identified through the Reference Center for Auto-Inflammatory Diseases and Amyloidosis and a systematic literature review was performed. RESULTS: Three new patients were identified: two with Familial Mediterranean fever (FMF) and one with cryopyrin-associated periodic syndrome; one was under anakinra therapy and one had received a kidney transplantation before her pregnancy. One patient was diagnosed with AAA following the detection of post-partum nephrotic syndrome. Among the 27 patients from literature and our case, FMF was the main cause of AAA (69%). Eight of the patients were diagnosed with AAA during their pregnancy or in immediate post-partum and gestational complications appeared in 23/25 cases, mostly intrauterine growth retardation (n = 10), prematurity (n = 11) and preeclampsia (n = 4). No bleeding complication was reported. CONCLUSION: Pregnancy can occur in patients (eight overall) with AAA and the diagnosis is frequently made during pregnancy. Pregnant women with AAA are at risk for adverse pregnancy-associated outcomes and require special and closer monitoring.

An accurate haplotyping method using multiplex pyrosequencing with AS-PCR to detect ABCB1 haplotypes associated with rivaroxaban-derived hemorrhagic events.

In clinical practice, owing to the comprehensive genetic insights they offer, haplotypes have attracted greater attention than individual single nucleotide polymorphisms (SNPs). Due to the long distances across SNP locations, detecting the haplotype using genomic DNA is challenging. Current haplotyping methods are either expensive and labor-intensive (high-throughput DNA sequencing), or haplotyping a single clinical sample (computational approach) is impossible. Herein, we propose using mRNA as a haplotyping target to minimize the distance among SNPs and employing allele-specific PCR (AS-PCR) to pick up a desired haplotype, followed by multiplex pyrosequencing to type the alleles at the SNP location of interest. AS-PCR was improved by combining an additional 3'-phosphorylated modified probe to achieve the specific separation of two closely similar templates. Only the sample with more than two heterozygotes needs to be haplotyped; therefore, we propose a stratification strategy to screen the samples for further haplotyping. This method was evaluated by associating ABCB1 haplotypes with the rivaroxaban-derived side effect in a cohort of 505 patients with nephrotic syndrome, focusing on the SNPs of ABCB1: rs1236C > T, rs2677G > T/A, and rs3435C > T. We successfully identified five bleeding-related haplotypes: rs1236T-rs2677T-rs3435T, rs1236C-rs2677G-rs3435T, rs1236T-rs2677G-rs3435C, rs1236C-rs2677G-rs3435C, and rs1236T-rs2677T-rs3435C. We compared the results with those from the conventional computational algorithm PHASE and observed that PHASE results dismissed the impact of rs1236C-rs2677G-rs3435C and rs1236C-rs2677G-rs3435T on bleeding risk and erroneously suggested a false positive association of rs1236C-rs2677A-rs3435T with increased bleeding risk.

A Case of Tiopronin-induced Membranous Nephropathy Presenting with IgG4-predominant Staining Pattern.

Tiopronin is a key drug used to treat cystinuria. A 41-year-old Japanese woman with cystinuria presented with eyelid edema and weight gain after the administration of tiopronin. Her serum albumin was 1.8 g/dL and her urinary protein level was 5.5 g/gCre. After cessation of tiopronin, she achieved remission of nephrotic syndrome (NS). Secondary NS due to tiopronin was evident based on the clinical course and laboratory values. A kidney biopsy showed membranous nephropathy (MN), and an immunofluorescence analysis revealed strong deposition of immunoglobulin G4 (IgG4). However, a previous case report of tiopronin-induced MN showed staining for IgG1 and IgG3. This case report suggests a novel etiology for tiopronin-induced MN.

[English Title : Treatment of membranous nephropathy]. / Comment je traite une glomérulonéphrite extra-membraneuse.

Membranous nephropathy (MN) is a frequent cause of nephrotic syndrome in adults. In recent years, many progresses have been made, both in terms of diagnosis and treatment. For diagnosis, the discovery of new antigens and diseases that may be associated with MN led to the establishment of a new classification of MNs. In terms of treatment, many progresses have also been made with increasingly effective management, particularly with the help of immunosuppressive drugs. However, there are still cases of MN refractory to conventional treatments. Numerous molecules are being developed to manage these refractory MNs. Among them, Obinutuzumab, a type II anti-CD20, allows a more profound depletion of B cells compared to Rituximab classically used in clinical routine. To illustrate this point, we present the case of a patient suffering from MN with anti-THSD7A antibodies in whom a clinical and biological improvement was observed with obinutuzumab, after failure of conventional therapies.

La glomérulonéphrite extra-membraneuse (GEM) est une cause fréquente de syndrome néphrotique de l'adulte. Au cours des dernières années, de nombreux progrès ont été réalisés, tant au niveau diagnostic que thérapeutique. D'un point de vue diagnostic, la découverte de nouveaux antigènes et de pathologies qui peuvent leur être associées a permis d'établir une nouvelle classification des GEM. Au niveau des traitements, de nombreux progrès ont également été réalisés, avec une prise en charge de plus en plus efficace, notamment à l'aide de traitements immunosuppresseurs. Cependant, il persiste des cas de GEM réfractaires aux traitements classiques. De nombreuses molécules sont en cours de développement pour permettre la prise en charge de ces GEM réfractaires. Parmi celle-ci, on retrouve l'obinutuzumab, un anti-CD20 de type II permettant une meilleure déplétion des cellules B que le rituximab déjà utilisé dans cette indication. Pour illustrer ce propos, nous présentons le cas d'un patient souffrant d'une GEM à anticorps anti-thrombospondine (THSD7A) chez lequel une amélioration clinique et biologique a été observée sous obinutuzumab, après échec des traitements conventionnels.

Chronic subdural hematoma that may be caused by nephrotic syndrome: a case report and literature review.

Background: Chronic subdural hematoma (CSDH) is a common complication of neurosurgery. Craniocerebral trauma is the likely cause. There are no reports relating CSDH with nephrotic syndrome. Its pathogenesis is very rare, and there are no previous reports on treatments for this disease. We report a case of chronic subdural hematoma that may be caused by nephrotic syndrome and review the previous literature on this subject. Case summary: We report a rare case of chronic subdural hematoma that may be caused by nephrotic syndrome. After the patient was admitted to the hospital, relevant laboratory tests were conducted, and a large amount of protein was detected in the patient's urine, indicating hypoproteinaemia and hyperlipidemia. The patient was diagnosed with nephrotic syndrome. After the exclusion of related surgical contraindications, the patient underwent trepanation and drainage of the chronic subdural hematoma. Subsequent treatment with oral atorvastatin was provided after surgery. The patient was transferred to the nephrology department for further treatment of nephrotic syndrome if his neurological condition improved. No neurological sequelae were detected at the follow-up visit 3 months after the operation. Conclusion: Chronic subdural hematomas are rarely caused by nephrotic syndrome. Trepanation and drainage may be considered for patients confirmed to have adequate hematoma liquefaction on imaging and who can tolerate craniotomy. Atorvastatin should be supplemented as prophylactic treatment after the operation. Nephrotic syndrome should be treated as soon as the patient's neurological condition is stable.

The risk of thromboembolic events in patients with nephrotic syndrome and relatively high albumin levels: a study over 10 years.

BACKGROUND: Low albumin level is a risk factor for thromboembolic events in patients with NS (nephrotic syndrome). However, little is known about the proportion and characteristics of patients with NS who experience thromboembolic events with relatively high albumin levels (≥ 25 g/L). Therefore, we explored the features of this specific group of patients. METHODS: This study included all hospitalized patients in our center for the past 10 years who had diagnoses of NS and relevant thromboembolic events. We divided them into 2 groups based on their serum albumin level when the thromboembolic event occurred. The clinical data were analyzed with SPSS software. RESULTS: There were 312 patients enrolled in our study. Eighty-four (26.9%) of them had relatively high albumin levels (≥ 25 g/L). Patients with NS with high albumin levels had significantly lower levels of 24-h proteinuria (P < 0.01) and a higher rate of autoimmune disease (P = 0.03) than the low-albumin group. Membranous nephropathy (MN) was the most frequent pathological type of NS in patients with thromboembolic events, regardless of their albumin level. There were significantly fewer patients with anti-PLA2R (M-type phospholipase A2 receptor)-positive MN in the high-albumin group than in the low-albumin group (P < 0.01). CONCLUSIONS: Our study found that there was still a high risk for patients with NS and relatively high albumin levels to develop thromboembolic events.

Association between Exclusive Breastfeeding and the Incidence of Childhood Nephrotic Syndrome.

OBJECTIVE: To assess the relationship between breastfeeding and the risk of developing nephrotic syndrome using a population-based nationwide birth cohort in Korea. STUDY DESIGN: This nationwide cohort study utilized data from the Korean National Health Information Database and the Korean National Health Screening Program for Infants and Children. The study included all children born between January 1, 2010, and December 31, 2018, who underwent their first health screening, which included a specific questionnaire on breastfeeding between 4 and 6 months of age. Associations between nephrotic syndrome and exclusive breastfeeding were estimated using adjusted hazard ratios (aHR) derived from Cox proportional hazards models, adjusted for sociodemographic variables, with follow-up until the occurrence of nephrotic syndrome, eight years post-index date, death, or December 31, 2022, whichever was first. RESULTS: The study population comprised 1,787,774 children (median follow-up: 7.96 years; IQR: 6.31-8.00 years), including 612,556 exclusively breastfed and 1,175,218 formula-fed children. Exclusive breastfeeding was associated with a decreased risk of developing nephrotic syndrome (aHR: 0.80; 95% CI: 0.69 - 0.93). Subgroup analysis stratified by sex mirrored the overall findings, although statistical significance was not observed in girls (boys: aHR, 0.75; 95% CI, 0.62-0.92; girls: aHR, 0.87; 95% CI, 0.70 - 1.09). Sensitivity analysis confirmed these results. CONCLUSION: Exclusive breastfeeding was associated with a 20% reduced risk of developing nephrotic syndrome up to 8 years of age.

Timing of relapse as a key indicator of steroid-sparing requirements in childhood idiopathic nephrotic syndrome.

BACKGROUND: Managing children with frequent relapses or steroid-dependent nephrotic syndrome poses challenges due to recurrent relapses necessitating prolonged steroid exposure, thus increasing susceptibility to long-term complications. Identifying those at risk of poor response to steroid therapy may be helpful to guide timely intervention with steroid-sparing agents. This study aimed to identify factors associated with steroid-sparing agent needs in children with frequent relapses or steroid-dependent nephrotic syndrome. METHODS: A retrospective multicenter cohort study was conducted by reviewing the medical records of children with idiopathic nephrotic syndrome treated between 2006 and 2023. Cox proportional regression analyzed prognostic factors for steroid-sparing agent requirements in children with frequent relapses or steroid-dependent nephrotic syndrome. The time-to-event analysis utilizing the Kaplan-Meier estimate examined the proportion of children needing steroid-sparing agents after diagnosis. RESULTS: Medical records of 121 children (85 males) diagnosed with idiopathic nephrotic syndrome at a median age of 4.5 years (range 1.3-12.8) were reviewed over a median follow-up of 3.7 years (range 1.0-15.0). Time to subsequent relapse post-frequent relapses or steroid-dependent nephrotic syndrome diagnosis (at 3-month threshold) emerged as the sole significant predictor of steroid-sparing agent requirement, adjusted hazard ratio (aHR) = 2.26, 95% confidence interval (CI) 1.26-4.05. Kaplan-Meier analysis indicated that an earlier first relapse (< 3 months) led to earlier steroid-sparing agent requirement (log-rank p = 0.005). Children who relapsed within 3 months post-frequent relapses or steroid-dependent nephrotic syndrome diagnosis exhibited a higher frequency of relapses, a greater incidence of steroid-related adverse events, and were more likely to develop steroid dependency. CONCLUSIONS: Early subsequent relapse following diagnosis of frequent relapses or steroid-dependent nephrotic syndrome was linked to earlier requirement of steroid-sparing agent therapy. Further prospective research is necessary to confirm this observation.

To biopsy or not to biopsy a teenager with idiopathic nephrotic syndrome? Biopsy first.

Kidney biopsy plays a crucial role in the diagnosis and management of several glomerular diseases. While it is generally considered a routine and safe procedure in children, it should be conducted with the primary objective of addressing the following question: do the prognosis and treatments vary based on the findings of kidney biopsy? In children presenting with idiopathic nephrotic syndrome (INS), guidelines suggest to consider kidney biopsy for individuals older than 12 years, primarily due to the possible increased incidence of different glomerulonephritis compared to younger patients, who predominantly manifest with minimal change disease. However, these guidelines also advocate for uniform therapeutic strategies, typically steroids, irrespective of the age or histological findings. Whether the age of more than 12 years may be a recommendation for performing kidney biopsy at presentation of INS is debatable. Instead, kidney biopsy could be reserved for steroid-resistant cases. On the other hand, when kidney biopsy is performed in INS, particularly in focal segmental glomerulosclerosis, histology may reveal additional lesions, that are strongly associated with a poorer response to treatment and worse clinical outcomes. Therefore, current guidelines on treatments of nephrotic syndrome may appear overly restrictive, despite the relevant findings provided by kidney biopsy. Therefore, in the present manuscript, which is part of a pro-con debate on the management of nephrotic syndrome in adolescents, we emphasize the potential role of performing a kidney biopsy before initiating corticosteroid treatment.

Risk Factors for Idiopathic Nephrotic Syndrome Relapse in Pediatric Age.

Introduction. Eighty percent of children with primitive nephrotic syndrome (NS) will have at least one relapse in their life. Specific risk factors could be associated with a higher incidence of relapses and a worse prognosis. This study aims to deepen the demographic and onset-related risk factors in children with known diagnosis of primitive NS attending the Pediatric Nephrology Unit of the University Hospital of Padua. Methods. Observational, descriptive study of all children (1-11 years old) with a known diagnosis of Primitive NS who attended our Pediatric Nephrology Unit between 1 January 2002 and 31 March 2023. Results. 49 patients were involved. 79.5% had at least one episode of NS relapse during their lifetime. 69.4% were classified as frequently relapsing or steroid-dependent NS. The relapse risk factor "non-Western ethnicity" was related to a worse prognosis and steroid-dependent NS classification (p = 0.041). The onset-related risk factor "thrombocytosis" appears to be related to a better prognosis (p = 0.03). Conclusion. The relapse risk factors "non-Western ethnicity" and "thrombocytosis" are characterized by worse and better prognosis, respectively. This evidence could support the follow-up of primitive NS in pediatric age.

Clinicopathological Pattern of Renal Biopsies in Children with Nephrotic Syndrome.

Background: A renal biopsy is essential for the identification and management of renal disorders. Although considered an invasive operation, it is necessary for a definitive diagnosis and treatment of many renal diseases. The primary goal of this study was to assess the clinicopathological aspect of renal diseases undergoing biopsy in children receiving tertiary care.Patients and Methods: Children (≤18 years) hospitalized with nephrotic syndrome were the subjects of this cross-sectional study, and comprehensive assessments confirmed the need for a kidney biopsy. Included were 277 children who met the inclusion and exclusion criteria. Data on patient outcomes, biopsy indications, complications, histopathologic results, and demographic information were documented.Results: Of the 277 patients who underwent renal biopsy, 63.2% were male, and 36.8% were female. Average age of the patients was 15 ± 2.9 years, with age distribution ranging from 3 to 18 years. The most frequent indication for renal biopsy was atypical age of <1 and >10-years-old (91.7%), steroid-resistant (5.1%), asymptomatic hematuria (21.3%), abnormal glomerular filtration rate (16.2%), and proteinuria (14.8%). The most common histopathological findings were focal segmental glomerulosclerosis (FSGS) (36.5%), followed by minimal change disease (MCD) (13.4%), membranoproliferative glomerulonephritis (MPGN) (10.5%), membranous glomerulonephritis (MGN) (7.94%), IgA nephropathy (IGAN) (7.58%), non-proliferative glomerulonephritis (NPGN) (7.58%), diffuse proliferative glomerulonephritis (DPGN) (6.9%), crescentic GN (5.8%), and systemic lupus erythematosus (SLE) (3.97%). The high frequency of positive samples was seen in SLE, followed by DPGN, MPGN, IGAN, and MGN. In contrast, MCD, crescentic GN, and NPGN showed negativity in all differential item functioning (DIF) parameters.Conclusion: Renal biopsy is a safe and effective procedure in the diagnosis and treatment of in children with nephrotic syndrome. FSGS had the highest frequency in examined biopsies.

Case report: membranoproliferative glomerulonephritis associated with Q fever causing chronic endocarditis.

BACKGROUND: Membranoproliferative glomerulonephritis is a rare entity which can be a result from autoimmune diseases, caused by various medications and infections. CASE PRESENTATION: We herein present the case of a 62-year-old male patient who presented with fatigue and was found to have severe anemia, impaired renal function, and nephrotic syndrome. A renal biopsy revealed membranoproliferative glomerulonephritis (MPGN) of the immune complex type with activation of the classical complement pathway. Further investigations led to the diagnosis of a chronic Coxiella burnetii-infection (Q fever), likely acquired during cycling trips in a region known for intensive sheep farming. Additionally, the patient was found to have a post endocarditic destructive bicuspid aortic valve caused by this pathogen. Treatment with hydroxychloroquine and doxycycline was administered for a duration of 24 months. The aortic valve was replaced successfully and the patient recovered completely. CONCLUSIONS: Early detection and targeted treatment of this life-threatening disease is crucial for complete recovery of the patient.

Immune landscape in the glomerular transcriptome of nephrotic syndrome and anca-associated vasculitis.

BACKGROUND: ANCA-associated vasculitis (AAV), and nephrotic syndrome encompassing diseases including minimal change disease (MCD), focal and segmental glomerulosclerosis (FSG), membranous nephropathy (MN), remain a challenge due to their varied immunological characteristics. Recent therapeutic advancements have highlighted the importance of understanding these diseases' immunological landscapes. METHODS: This study analyzed transcriptomics data from renal glomerular tissues of patients with AAV, FSG, MCD, MN, and normal controls. Utilizing an immune-related gene set of 883 genes, methods including Gene Set Variation Analysis (GSVA), LASSO regression, and Weighted Correlation Network Analysis (WGCNA) were used. Predictions of immune cell compositions were made through CIBERSORT, TIMER, MCPcounter, and quanTIseq algorithms. RESULTS: The study revealed distinct immunogenetic pathways enriched in each disease: hematopoietic cell lineage in ANCA, linoleic acid metabolism in FSG, PPAR signaling in MCD, and drug metabolism in MN. Classifiers based on immune gene expression showed high accuracy (AUC: ANCA 0.812, FSG 0.99, MCD 1, MN 0.888). Co-expression modules and PPI networks highlighted unique pathways for each disease. Predictions of immune cell composition showed elevated macrophages in FSG and MN, with Treg levels elevated across all four diseases compared to normal controls and highest in FSG. Correlation analyses demonstrated significant associations between classifier scores and immune cell types. CONCLUSION: This study offers accurate classifiers for AAV, FSG, MCD, and MN, and reveals distinct immunological pathways. These findings advance personalized treatments and highlight potential therapeutic targets in AAV and nephrotic syndrome. Further research should validate these results for clinical applications.

A child with systemic onset juvenile idiopathic arthritis and nephrotic syndrome.

INTRODUCTION: Amyloidosis of the kidney is a rare complication in children with juvenile idiopathic arthritis (JIA), more commonly seen with systemic onset juvenile idiopathic arthritis (SOJIA). It usually presents with asymptomatic proteinuria. CASE REPORT: An 11.5-year-old boy with onset of SOJIA at 6 years of age came to our clinic with anasarca. Urinalysis and serum albumin suggested a diagnosis of nephrotic syndrome (NS) and kidney biopsy confirmed amyloidosis deposits. Treatment with injection tocilizumab was initiated. The proteinuria has decreased, and kidney functions are normal. CONCLUSION: Children with SOJIA should be monitored for proteinuria so that they can be offered timely appropriate therapy.

To biopsy or not to biopsy a teenager with typical idiopathic nephrotic syndrome? Start steroids first.

It is well known that minimal change disease (MCD) and focal segmental glomerulosclerosis are the most common histopathology findings in children with idiopathic nephrotic syndrome. Moreover, several studies demonstrated that MCD is associated with high steroid-responsiveness and a low incidence of kidney failure, suggesting that routine kidney biopsy is not warranted. Over time, the indications for performing a kidney biopsy have become increasingly stringent, aiming to limit unnecessary invasive procedures in the paediatric population. The most recent guidelines state that a kidney biopsy is not usually necessary at disease onset. Still, it should be performed in case of atypical features suggestive of systemic diseases or glomerulonephritis and in case of steroid-resistance, to assess the different differential diagnoses, regardless of patient age. Moreover, it has been shown that the best prognostic marker in childhood nephrotic syndrome is response to treatment and that kidney histology is not accurate in predicting prognosis. Furthermore, a kidney biopsy is not necessary to predict the relapsing course. Notably, kidney biopsy is an invasive procedure and may lead to significant complications. Finally, novel non-invasive biomarkers have been validated or are in the process of being approved to guide differential diagnoses and thus limit the need for kidney biopsies in patients with typical nephrotic syndrome. In the following sections, we aim to explain why initiating steroid treatment as the initial approach in teenagers with typical nephrotic syndrome is a reasonable strategy. Additionally, we explore how kidney biopsy indications may be alleviated in this population.

Short segment myelitis as a dominant manifestation of cryptococcal infection: a case report.

Cryptococcal infection of central nervous system commonly involves meningitis or meningoencephalitis, but rarely mimics inflammatory myelitis. We present short segment myelitis as a dominant manifestation caused by Cryptococcus neoformans in a patient with nephrotic syndrome under immunosuppressive therapy. This case report highlights Cryptococcus neoformans as a potential etiological factor for short segment myelitis in immunocompromised hosts.