Clinical Analysis of Primary Nephrotic Syndrome Complicated by Plastic Bronchitis in Children.

OBJECTIVE: To summarize the clinical features of primary nephrotic syndrome (PNS) complicated by plastic bronchitis (PB) in children to provide guidance for treatment. METHODS: We conducted a retrospective review of the clinical data of 25 children hospitalized with NS complicated by PB in our Hospital between 10/2016 and 03/2019, and summarized the clinical manifestations, imaging and fiberoptic bronchoscopy (FOB) examinations, treatment course and outcome of them. RESULTS: 1). The 25 children, with a nephrotic syndrome (NS) course of one to 36 months, were all diagnosed with PB after FOB, among which 8 cases (32%) had respiratory failure and required ventilatory support. All of them started with respiratory symptoms such as fever and cough, and then suffered from dyspnea and progressive aggravation after 1-3 day(s) of onset, with rapid occurrence of bidirectional dyspnea and even respiratory failure in severe cases. 2). Laboratory test for pathogens: influenza A virus H1N1 (11 cases), influenza B virus (9 cases), adenovirus (3 cases) and mycoplasma pneumoniae (2 cases). There was no statistically significant difference (P>0.05) between children with common NS complicated by influenza virus (IV) infection (not accompanied by dyspnea) and those with kidney disease who developed PB in the white blood cell count, lymphocyte count, the inflammatory biomarkers C-reactive protein (CRP), procalcitonin (PCT) and humoral immunity (IgG level), yet the total IgG level was found significantly higher and the blood albumin level lower in the latter (P<0.05). 3). The 25 children were all examined with the FOB and treated with lavage, 15 of which had typical bronchial tree-like casts and 10 broken and stringy casts. Based on histopathological classification, all children were of Type I. 4). Twenty children (80%) with influenza were administered the antiviral drug Oseltamivir, 20 (80%) were treated with antibiotics, oral hormones were replaced with the same dosage of intravenous Methylprednisolone for 5 cases (20%), and 20 (80%) were intravenously administered gamma globulins (400-500 mg/kg x 3 days). These children showed a remarkable improvement after treatment and there were no deaths. CONCLUSION: NS children are at high risk of influenza virus infection. Children with a severe case of NS are more susceptible to PB. If symptoms like shortness of breath, wheezing and progressive bidirectional dyspnea occur, FOB examination and lavage treatment should be performed as early as possible. Hyper-IgE-emia and hypoproteinemia may be the high risk factors for PNS complicated by PB in children. ZIEL: Ziel der Studie war es, durch Zusammenfassung der klinischen Merkmale des primären nephrotischen Syndroms (PNS) mit komplizierender plastischer Bronchitis (PB) im Kindesalter eine Orientierungshilfe für die Therapie der Erkrankung zu geben. METHODIK: Wir führten eine retrospektive Prüfung der klinischen Daten von 25 Kindern durch, die zwischen Oktober 2016 und März 2019 in unser Krankhaus aufgenommen wurden, und erstellten eine Zusammenfassung der klinischen Symptome, Untersuchungen mit bildgebenden Verfahren und fiberoptischer Bronchoskopie (FOB), des Therapieverlaufs und des Outcomes der Patienten. ERGEBNISSE: 1). Bei den 25 Kindern bestand ein nephrotisches Syndrom (NS) über einen Zeitraum von einem bis 36 Monaten. Bei allen Patienten wurde die Diagnose PB nach FOB gestellt, wobei in 8 Fällen (32%) eine beatmungspflichtige respiratorische Insuffizienz vorlag. Alle Patienten zeigten anfänglich Symptome einer Atemwegserkrankung wie Fieber und Husten, gefolgt von Atemnot und progredienter Verschlechterung 1 bis 3 Tage nach Erkrankungsbeginn. Dabei kam es rasch zum Auftreten bidirektionaler Atemnot, in schweren Fällen bis hin zur respiratorischen Insuffizienz. 2). Laboruntersuchung auf Erreger: Influenza-A-Virus H1N1 (11 Fälle), Influenza-B-Virus (9 Fälle), Adenovirus (3 Fälle) und Mycoplasma pneumoniae (2 Fälle). Es fand sich kein statistisch signifikanter Unterschied (P>0,05) zwischen Kindern, die ein "gewöhnliches" NS mit komplizierender Influenza-Virus (IV)-Infektion (ohne begleitende Atemnot) aufwiesen, und Kindern mit Nierenerkrankung, die eine PB entwickelten, hinsichtlich der Leukozyten- und Lymphozytenwerte sowie der Entzündungsmarker C-reaktives Protein (CRP), Procalcitonin (PCT) und humorale Immunität (IgG-Wert). Allerdings wurde bei der letzteren Patientengruppe ein signifikant höherer Gesamt-IgG-Wert und ein signifikant niedriger Albumin-Spiegel im Blut nachgewiesen (P<0.05). 3). Bei allen 25 Kindern erfolgte eine FOB und Therapie mit Lavage, bei 15 Kinder fanden sich typische verzweigte Ausgüsse der Bronchialäste und bei 10 Patienten desintegrierte und zähe Ausgüsse. Gemäß der histopathologischen Klassifikation waren alle Kinder vom Typ I. 4). Zwanzig Kinder (80%) mit Influenza erhielten das Virostatikum Oseltamivir, 20 Kinder (80%) eine Antibiotikatherapie, in 5 Fällen (20%) wurden oral gegebene Hormone durch intravenös in derselben Dosis verabreichtes Methylprednisolon ersetzt und 20 Kinder (80%) erhielten intravenös verabreichte Gammaglobuline (400-500 mg/kg Körpergewicht x 3 Tage). Diese Kinder zeigten eine bemerkenswerte Verbesserung nach der Therapie und es traten keine Todesfälle auf. SCHLUSSFOLGERUNG: Bei Kindern mit NS besteht ein hohes Risiko für eine Influenza-Virus-Infektion. Kinder mit schwerem NS sind anfälliger für PB. Bei Auftreten von Symptomen wie Atemnot, Giemen und Brummern sowie progredienter bidirektionaler Dyspnoe sollte baldmöglichst eine FOB-Untersuchung und eine therapeutische Lavage durchgeführt werden. Erhöhte IgE-Werte im Blut und Hypoproteinämie stellen möglicherweise Risikofaktoren für PNS mit komplizierender PB im Kindesalter dar.

Effects of the mTOR Pathway on the Balance of Th2/Treg Cells in Children with Idiopathic Nephrotic Syndrome.

Introduction: Immune dysfunction contributes to the progression of idiopathic nephrotic syndrome (INS), but the details of the pathogenesis of progression remain unknown. This study of children with INS investigated the relationship of activation of the mechanistic target of rapamycin (mTOR) pathway (PI3K/AKT/mTOR/p70S6K) with the levels of T helper 2/regulatory T (Th2/Treg) cells. Materials and Methods: Twenty children with active INS (before steroid treatment), 20 children with remitting INS (INS-R, after steroid treatment), and 20 healthy control children (Ctrl) were enrolled. The levels of Th2/Treg cells in their peripheral circulatory systems were measured using flow cytometry, and the concentration of interleukin (IL)-4 was determined using a cytometric bead array (CBA). The levels of PI3K, AKT, mTOR, p70S6K, and transcription factors associated with Th2/Treg cells were measured using real-time polymerase chain reaction. Results: The INS group had a greater proportion of circulating Th2 cells; level of IL-4 protein; and levels of GATA, PI3K, AKT, mTOR, and p70S6K mRNAs than the Ctrl group (all P < 0.05), but a lower proportion of circulating Tregs and expression of Foxp3 (both P < 0.05). Patients in the INS-R group had normalization of these markers (all P < 0.05). Patients in the INS group had negative correlation in the percentage of Treg cells with Th2 cells and with IL-4 level and a negative correlation in the levels of GATA3 and Foxp3 mRNAs. Conclusions: Patients with active INS had an imbalance of Th2/Treg cells, which might result from the aberrant signaling of the mTOR pathway (PI3K/AKT/mTOR/p70S6K).

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

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

Function of miR-24 and miR-27 in Pediatric Patients With Idiopathic Nephrotic Syndrome.

Purpose: We investigated the pathogenesis of idiopathic nephrotic syndrome (INS) by measuring the effects two specific miRNAs on Th2 cells in children with this disease. Methods: After informed consent, we enrolled 20 children with active INS before steroid initiation, 20 children with INS in remission after steroid therapy, and 20 age-matched healthy controls. Flow cytometry was used to measure the levels of Th2 cells and a cytometric bead array was used to measure the levels of IgE, interleukin (IL)-4, and IL-13. RT-PCR was used to measure the levels of miR-24 and miR-27 in CD4+TCD25- cells. PBMCs were isolated using Ficoll density gradient centrifugation, and transfected with different mimic or inhibitor miRNAs. RT-PCR was used to measure the expression of different RNAs, and flow cytometry was used to determine the percentage of Th2 cells. Results: Relative to healthy controls, children with active INS had higher percentages of Th2 cells (P < 0.05), but there was no significant difference in controls and children in remission. The plasma levels of IgE, IL-4, and IL-13 were significantly increased in children with active INS (P < 0.05). There were lower levels of miR-24 and miR-27 in children with active non-atopic INS (P < 0.05). Transfection experiments indicated that upregulation of each miRNA decreased the percentage of Th2 cells and the level of IL-4 (P < 0.05), and down-regulation of each miRNA had the opposite effects (P < 0.05). Conclusion: Children with active INS, with or without atopy, had higher levels of IgE, possibly related to their higher levels of IL-13 and IL-4 due to a drift toward Th2 cells. miR-24 and miR-27 suppressed the expression of Th2 cells and have a critical function regulating Th2 cell expression in INS.

The effects of ketogenic diet on the Th17/Treg cells imbalance in patients with intractable childhood epilepsy.

PURPOSE: The ketogenic diet (KD) is an effective treatment for intractable epilepsy (IE), however the therapeutic mechanism is still unclear. This study was designed to investigate T helper type 17/regulatory T cell (Th17/Treg) levels in children with IE and age-matched healthy controls following KD. METHOD: Circulating levels of Th17/Treg cells were analyzed by flow cytometry. Plasma concentration of interleukin (IL)-17 was measured by cytometric bead array assay. Real-time PCR was performed to measure mRNA levels of mTOR, HIF1α and Th17/Treg associated factors in purified CD4(+)CD25(+) T and CD4(+)CD25(-) T cells. RESULTS: By one-way ANOVA, the proportion of circulating Th17 cells and expression of IL-17A and RORγt were significantly higher (P<.05), while the proportion of circulating Tregs and expression of Foxp3, GITR, CTLA-4 were significantly lower (P<.05) in IE patients than healthy subjects. However, these alternations were reversed following KD (P<.05). In CD4(+)CD25(+) T and CD4(+)CD25(-) T cells mTOR and HIF1α expression were significantly higher in IE patients (P<.05), however KD reduced mTOR and HIF1α expression (P<.05). The plasma IL-17A concentrations were higher in IE patients than controls (P<.05). KD partially reduced IL-17A levels (P<.05). CONCLUSION: Our results suggest that Th17/Treg imbalance is characteristic of childhood IE, and may contribute to IE pathogenesis. KD treatment is able to correct this imbalance, probably via inhabiting the mTOR/HIF-1α signaling pathway.