Outcomes of children with idiopathic steroid resistant nephrotic syndrome: a single centre observational study / Desfechos de crianças com síndrome nefrótica idiopática córtico-resistente: um estudo observacional de centro único

ABSTRACT Introduction: Idiopathic steroid resistant nephrotic syndrome (SRNS) has variable outcomes in children. The primary objective of the present study was to assess the cumulative remission rate and the secondary objectives were to assess factors affecting the remission status, kidney function survival, and adverse effects of medications. Methods: One hundred fourteen patients with SRNS were included. Calcineurin inhibitor-based treatment protocol along with prednisolone and angiotensin-converting enzyme inhibitor were used, and patients were followed over 5 years. Results: Median age was 4.5 years; 53.5% of cases were between 1 to 5 years of age. Sixty-two patients (54.4%) were at initial stage and 52 (45.6%) were at a late SRNS stage. Median eGFRcr was 83.5 mL/min/1.73m2 at presentation. Of the 110 patients, 63 (57.3%) achieved remission [complete remission 30 (27.3%), partial remission 33 (30%)], and 47 (42.7%) had no remission. Kidney function survival was 87.3% and 14 cases (12.7%) had progression to CKD (G3-8, G4-3, G5-1, and G5D-2). Median duration of follow up was 36 months (IQR 24, 60). Age of onset, cyclosporine/tacrolimus, eGFRcr, and histopathology (MCD/FSGS) did not affect remission. Similarly, remission status in addition to age of onset, drug protocol, and histopathology did not significantly affect kidney function during a period of 5 years. Hypertension, cushingoid facies, short stature, cataract, and obesity were observed in 37.7, 29.8, 25.5, 17.5, and 0.7% of cases, respectively. Conclusion: About half of the cases achieved remission. Age of onset of disease, cyclosporine/tacrolimus use, and histopathological lesion neither affected remission status nor short-term kidney function survival in SRNS.

RESUMO Introdução: A síndrome nefrótica idiopática córtico-resistente (SNICR) apresenta desfechos variáveis em crianças. O objetivo principal deste estudo foi avaliar a taxa de remissão cumulativa. Os objetivos secundários foram avaliar fatores que afetam status de remissão, sobrevida da função renal e efeitos adversos de medicamentos. Métodos: Foram incluídos 114 pacientes com SNCR. Utilizou-se protocolo de tratamento baseado em inibidores de calcineurina juntamente com prednisolona e inibidor da enzima conversora de angiotensina. Os pacientes foram acompanhados durante 5 anos. Resultados: A idade mediana foi 4,5 anos; 53,5% dos casos tinham entre 1 e 5 anos. 62 pacientes (54,4%) estavam em estágio inicial; 52 (45,6%) em estágio tardio da SNCR. A TFGecr mediana foi 83,5 mL/min/1,73 m2 na apresentação. Dos 110 pacientes, 63 (57,3%) alcançaram remissão [remissão completa 30 (27,3%), remissão parcial 33 (30%)], e 47 (42,7%) não apresentaram remissão. A sobrevida da função renal foi 87,3%; 14 casos (12,7%) progrediram para DRC (G3-8, G4-3, G5-1, G5D-2). A duração mediana do acompanhamento foi 36 meses (IIQ 24, 60). Idade no início, ciclosporina/tacrolimus, TFGecr e histopatologia (DLM/GESF) não afetaram a remissão. Igualmente, status de remissão, além da idade no início, protocolo de medicamentos e histopatologia não afetaram significativamente a função renal por 5 anos. Observou-se hipertensão, fácies cushingoide, baixa estatura, catarata e obesidade em 37,7; 29,8; 25,5; 17,5; e 0,7% dos casos, respectivamente. Conclusão: Aproximadamente metade dos casos alcançou remissão. Idade no início, uso de ciclosporina/tacrolimus e lesão histopatológica não afetaram o status de remissão nem a sobrevida da função renal a curto prazo na SNICR.

Outcomes of children with idiopathic steroid resistant nephrotic syndrome: a single centre observational study.

INTRODUCTION: Idiopathic steroid resistant nephrotic syndrome (SRNS) has variable outcomes in children. The primary objective of the present study was to assess the cumulative remission rate and the secondary objectives were to assess factors affecting the remission status, kidney function survival, and adverse effects of medications. METHODS: One hundred fourteen patients with SRNS were included. Calcineurin inhibitor-based treatment protocol along with prednisolone and angiotensin-converting enzyme inhibitor were used, and patients were followed over 5 years. RESULTS: Median age was 4.5 years; 53.5% of cases were between 1 to 5 years of age. Sixty-two patients (54.4%) were at initial stage and 52 (45.6%) were at a late SRNS stage. Median eGFRcr was 83.5 mL/min/1.73m2 at presentation. Of the 110 patients, 63 (57.3%) achieved remission [complete remission 30 (27.3%), partial remission 33 (30%)], and 47 (42.7%) had no remission. Kidney function survival was 87.3% and 14 cases (12.7%) had progression to CKD (G3-8, G4-3, G5-1, and G5D-2). Median duration of follow up was 36 months (IQR 24, 60). Age of onset, cyclosporine/tacrolimus, eGFRcr, and histopathology (MCD/FSGS) did not affect remission. Similarly, remission status in addition to age of onset, drug protocol, and histopathology did not significantly affect kidney function during a period of 5 years. Hypertension, cushingoid facies, short stature, cataract, and obesity were observed in 37.7, 29.8, 25.5, 17.5, and 0.7% of cases, respectively. CONCLUSION: About half of the cases achieved remission. Age of onset of disease, cyclosporine/tacrolimus use, and histopathological lesion neither affected remission status nor short-term kidney function survival in SRNS.

Persistence of behavioral abnormalities following corticosteroid therapy in children with initial episode of idiopathic nephrotic syndrome: a prospective longitudinal observation / Persistência de anormalidades comportamentais após corticoterapia em crianças com episódio inicial de síndrome nefrótica idiopática: uma observação longitudinal prospectiva

Abstract Introduction: Treatment of nephrotic syndrome with corticosteroid can cause several side- effects including behavioral abnormalities. The objectives of the study were to observe the proportion of non-relapsers having persistence of behavioral abnormalities after completion of treatment of initial episode and compare the abnormalities with relapsers, and to determine risk factors for persistence. Methods: Seventy-five children with a first episode of idiopathic nephrotic syndrome and 60 normal children were rated by parents for behavioral problems using the Child Behavior Checklist. The Parenting Stress Index was also evaluated. The children were rated before treatment and 12 and 36 weeks after. Results: Both relapsers and non-relapsers showed abnormalities in internalizing and externalizing domains at 12 weeks of steroid therapy. Non-relapsers had abnormal scores in the internalizing domain in 63.5 % and externalizing domain in 48.1% of cases at 36 weeks. Relapsers had abnormal scores in all the three behavior domains, but a significantly higher proportion of relapsers had abnormal scores regarding total behavior (65.2% vs 28.8%, p<0.01) and child domains (100% vs 57.7%, p<0.001) of Parenting Stress Index in comparison to non-relapsers at 36 weeks. Occurrence of relapse increased the risk (odds ratio 5.76, 95% CI 1.35-10.76, p< 0.001) for persistence of abnormal total behavior at 36 weeks follow-up. Conclusion: Persistence of abnormalities was observed not only in relapsers but also in non-relapsers. Relapse was found to be a significant risk factor for persistence of abnormal behaviors in these patients.

Resumo Introdução: O tratamento da síndrome nefrótica com corticosteroide pode causar vários efeitos colaterais, incluindo anormalidades comportamentais. Os objetivos do estudo foram observar a proporção de não-recidivos com persistência de anormalidades comportamentais após conclusão do tratamento do episódio inicial, comparar as anormalidades com os recidivos, e determinar fatores de risco para persistência. Métodos: 75 crianças com primeiro episódio de síndrome nefrótica idiopática e 60 crianças normais foram avaliadas pelos pais por problemas comportamentais usando o Checklist de Comportamento Infantil. O Índice de Estresse Parental também foi avaliado. As crianças foram avaliadas antes do tratamento, 12 e 36 semanas após. Resultados: Tanto recidivos quanto não recidivos mostraram anormalidades nos domínios de internalização e externalização às 12 semanas de terapia com esteroides. Não-recidivos apresentaram pontuações anormais no domínio de internalização em 63,5%, e no domínio de externalização, em 48,1% dos casos em 36 semanas. Recidivos tiveram pontuações anormais em todos os três domínios de comportamento, mas uma proporção significativamente maior de recidivos apresentou pontuações anormais em relação ao comportamento total (65,2% vs 28,8%, p<0,01) e domínios infantis (100% vs 57,7%, p<0,001) do Índice de Estresse Parental em comparação com não recidivos às 36 semanas. A ocorrência de recidiva aumentou o risco (odds ratio 5,76, 95% IC 1,35-10,76, p< 0,001) de persistência de comportamento total anormal em 36 semanas de acompanhamento. Conclusão: A persistência de anormalidades foi observada não apenas em recidivos, mas também em não recidivos. A recidiva foi um fator de risco significativo para a persistência de comportamentos anormais nesses pacientes.

Cerebrospinal Fluid Leucine-Rich Alpha-2 Glycoprotein (LRG) Levels in Children with Acute Bacterial Meningitis.

This study evaluated the diagnostic role of cerebrospinal fluid leucine-rich alpha-2 glycoprotein (CSF LRG) concentration in children with acute bacterial meningitis, and its role in differentiation from aseptic meningitis. CSF LRG concentration was measured by ELISA Kit of 50 children with bacterial meningitis, 16 aseptic meningitis, and 20 children with normal CSF; control. CSF LRG was significantly elevated (p < 0.001) in bacterial meningitis with a sensitivity, specificity, PPV, and NPV of 96%, 100%, 100%, and 90.9%, respectively at a cutoff of 110.0 ng/mL, based on ROC curve. At the same cutoff value, CSF LRG has sensitivity, specificity, PPV, and NPV of 96%, 75%, 92.3%, and 85.7%, respectively in differentiating bacterial from aseptic meningitis. However, sensitivity, specificity, PPV, and NPV at 139.9 ng/mL for differentiating between definite and probable bacterial meningitis were 88%, 75%, 79.1%, and 84.9%, respectively. CSF LRG should be used as a diagnostic biomarker for bacterial meningitis.

Persistence of behavioral abnormalities following corticosteroid therapy in children with initial episode of idiopathic nephrotic syndrome: a prospective longitudinal observation.

INTRODUCTION: Treatment of nephrotic syndrome with corticosteroid can cause several side- effects including behavioral abnormalities. The objectives of the study were to observe the proportion of non-relapsers having persistence of behavioral abnormalities after completion of treatment of initial episode and compare the abnormalities with relapsers, and to determine risk factors for persistence. METHODS: Seventy-five children with a first episode of idiopathic nephrotic syndrome and 60 normal children were rated by parents for behavioral problems using the Child Behavior Checklist. The Parenting Stress Index was also evaluated. The children were rated before treatment and 12 and 36 weeks after. RESULTS: Both relapsers and non-relapsers showed abnormalities in internalizing and externalizing domains at 12 weeks of steroid therapy. Non-relapsers had abnormal scores in the internalizing domain in 63.5 % and externalizing domain in 48.1% of cases at 36 weeks. Relapsers had abnormal scores in all the three behavior domains, but a significantly higher proportion of relapsers had abnormal scores regarding total behavior (65.2% vs 28.8%, p<0.01) and child domains (100% vs 57.7%, p<0.001) of Parenting Stress Index in comparison to non-relapsers at 36 weeks. Occurrence of relapse increased the risk (odds ratio 5.76, 95% CI 1.35-10.76, p< 0.001) for persistence of abnormal total behavior at 36 weeks follow-up. CONCLUSION: Persistence of abnormalities was observed not only in relapsers but also in non-relapsers. Relapse was found to be a significant risk factor for persistence of abnormal behaviors in these patients.

Risk factors for mortality in critically ill infants with acute kidney injury: A resource-limited setting experience.

Infants with acute kidney injury (AKI) who are critically ill often will have multiorgan dysfunctions. Objective of the present study was to find out mortality, recovery of kidney function at discharge and at 3 months, and to determine risk factors for mortality. Fifty-two infants (24 newborns and 28 postneonatal) with AKI were included. Staging was done as per Kidney Disease Improving Global Outcomes classification. Patients were subjected to medical treatment and peritoneal dialysis (PD), wherever indicated. Kidney function tests were performed at admission, discharge, and at 3 months follow-up. Median age of neonates was 8 days and postneonatal infants were 4.5 months. Stage 1, 2, and 3 AKI were present in 14 (26.9%), 16 (30.7%), and 22 (42.3%) cases, respectively. PD was required in 22 (42.3%) infants, and significantly higher in postneonatal than in neonates (57.1% vs. 25%, p < 0.05). Significant recovery of kidney function occurred at discharge and cases had normal parameters at 3 months. Mortality was 17.3%. Patients had significantly higher risk of mortality, if they had metabolic acidosis (OR 13.22, CI 2.33-74.94, p = 0.002) and needed ventilation (OR 14.93, 95% CI 1.7-130.97, p = 0.006) and PD (OR 6.53, 95% CI 1.20-35.48, p = 0.026). In logistic regression analysis, fluid overload (p < 001), hypotension (p < 0.01), and higher PRISM-III score (p < 0.05) were found as significant risk factors for mortality. Medical management including PD led to good recovery of kidney function. Presence of fluid overload, hypotension, and higher PRISM-III score adversely affected the outcome.

Fibroblast Growth Factor 23 Level and Cardiovascular Parameters in Children with Chronic Kidney Disease.

OBJECTIVE: To find out the serum fibroblast growth factor 23 (FGF-23) levels in different grades of CKD, and the prevalence of abnormal left ventricular mass index (LVMI), carotid intima-medial thickness (cIMT), and central pulse wave velocity (cPWV) and the risk factors including FGF-23 for these abnormalities. METHODS: Fifty-nine patients of CKD with G2 to G5, aged 2-18 y were included. The LVMI, cIMT, and cPWV were measured using standard techniques, and serum intact FGF-23 levels were estimated at enrollment. RESULTS: Median FGF-23 levels were significantly raised in all the grades of CKD than controls (p < 0.001), and also in G4 and G5 in comparison to G2&3 and in G5D than G5. Increased LVMI in 42 (71.2%), elevated cIMT in 30 (57.7%), and cPWV in 14 (26.9%) patients were found. The FGF-23 showed significant negative correlation with eGFRcr and positive with serum iPTH, phosphate and alkaline phosphatase levels, but had no correlations with LVMI, cIMT SDS, and cPWV SDS. Only systolic BP SDS (odds ratio 1.5, 95% CI 1.008-2.231, p = 0.046) was observed as a significant predictor for increased cIMT, while no variables had any association with abnormal LVMI and cPWV. CONCLUSIONS: Serum FGF-23 showed higher levels with increasing grades of CKD, but no significant association with cardiovascular parameters. Systolic BP SDS was found as a significant risk factor for increased cIMT in children with CKD.

Copper Oxide Nanoparticle-Induced Acute Inflammatory Response and Injury in Murine Lung Is Ameliorated by Synthetic Secoisolariciresinol Diglucoside (LGM2605).

Metal-oxide nanoparticles (MO-NPs), such as the highly bioreactive copper-based nanoparticles (CuO-NPs), are widely used in manufacturing of hundreds of commercial products. Epidemiological studies correlated levels of nanoparticles in ambient air with a significant increase in lung disease. CuO-NPs, specifically, were among the most potent in a set of metal-oxides and carbons studied in parallel regarding DNA damage and cytotoxicity. Despite advances in nanotoxicology research and the characterization of their toxicity, the exact mechanism(s) of toxicity are yet to be defined. We identified chlorination toxicity as a damaging consequence of inflammation and myeloperoxidase (MPO) activation, resulting in macromolecular damage and cell damage/death. We hypothesized that the inhalation of CuO-NPs elicits an inflammatory response resulting in chlorination damage in cells and lung tissues. We further tested the protective action of LGM2605, a synthetic small molecule with known scavenging properties for reactive oxygen species (ROS), but most importantly, for active chlorine species (ACS) and an inhibitor of MPO. CuO-NPs (15 µg/bolus) were instilled intranasally in mice and the kinetics of the inflammatory response in lungs was evaluated 1, 3, and 7 days later. Evaluation of the protective action of LGM2605 was performed at 24 h post-challenge, which was selected as the peak acute inflammatory response to CuO-NP. LGM2605 was given daily via gavage to mice starting 2 days prior to the time of the insult (100 mg/kg). CuO-NPs induced a significant inflammatory influx, inflammasome-relevant cytokine release, and chlorination damage in mouse lungs, which was mitigated by the action of LGM2605. Preventive action of LGM2605 ameliorated the adverse effects of CuO-NP in lung.

Clinical Profile and Outcome of Brain Abscess in Children from a Tertiary Care Hospital in Eastern Uttar Pradesh.

BACKGROUND AND AIMS: Brain abscess is a serious and dreadful disease presenting at tertiary centre. The objective of this study was to look into the clinical profile, predisposing conditions, microbiology and outcome of children suffering from brain abscess. METHODS: 30 children up to 18 years with clinical and imaging evidence of brain abscess were taken for study. Patients were stabilized as per unit protocol. Necessary investigations were carried out. Neuroimaging (CT or MRI) was used to confirm the diagnosis. All parameters (clinical, investigation, outcome) were recorded in predesigned performa. Neurosurgery consultation was sought in patients with multiple abscesses, posterior fossa abscesses, abscess with air-fluid level and causing midline shift. RESULTS: There were 16 males with 13 patients in age group (5-10 years). Mean duration of stay in hospital was 14.8 days. Most common predisposing factor was chronic suppurative otitis media (n-15). Typically, patients presented with fever, headache and seizures. On examination, motor deficits were the most common followed by signs of meningitis. Computerized tomography confirmed the diagnosis in most cases. Temporal lobe (n-11) was the commonest intracranial site for the abscess. Methicillin resistant staphylococcus and proteus mirabilis were the common pathogen isolated from blood and pus. Blood culture positivity rate was 16.7% and pus culture positivity rate was 25%. All cases were managed with intravenous antibiotics and aspiration (n-10) and excision (n-6). There were 5 deaths. There was complete immediate recovery in 13 cases with residual motor deficit in 12 cases. CONCLUSION: Brain abscess is a rare but serious entity in children. Late diagnosis and improper management leads to poor outcome. Early surgical intervention is helpful. Threshold for diagnosis should be low in children with chronic ear infection and congenital heart diseases.

Managing Children With Renal Diseases During the COVID-19 Pandemic.

The coronavirus outbreak is a rapidly evolving pandemic, placing unprecedented strain on health-care systems. COVID-19 presents challenges for management of children with renal diseases, especially those receiving long-term immunosuppressive medications, including renal transplant recipients and those with chronic kidney disease and acute kidney injury requiring dialysis. Our preparedness for managing this vulnerable group of children is the need of the hour. The purpose of this article is to provide guidance to caregivers and health care personnel involved in management of children with renal diseases and to ensure patient well-being, while protecting staff from infection.

Radiation activates myeloperoxidase (MPO) to generate active chlorine species (ACS) via a dephosphorylation mechanism - inhibitory effect of LGM2605.

BACKGROUND: Radiation exposure of tissues is associated with inflammatory cell influx. Myeloperoxidase (MPO) is an enzyme expressed in granulocytes, such as neutrophils (PMN) and macrophages, responsible for active chlorine species (ACS) generation. The present study aimed to: 1) determine whether exposure to γ-irradiation induces MPO-dependent ACS generation in murine PMN; 2) elucidate the mechanism of radiation-induced ACS generation; and 3) evaluate the effect of the synthetic lignan LGM2605, known for ACS scavenging properties. METHODS: MPO-dependent ACS generation was determined by using hypochlorite-specific 3'-(p-aminophenyl) fluorescein (APF) and a highly potent MPO inhibitor, 4-aminobenzoic acid hydrazide (ABAH), and confirmed in PMN derived from MPO-/- mice. Radiation-induced MPO activation was determined by EPR spectroscopy and computational analysis identified tyrosine, serine, and threonine residues near MPO's active site. RESULTS: γ-radiation increased MPO-dependent ACS generation dose-dependently in human MPO and in wild-type murine PMN, but not in PMN from MPO-/- mice. LGM2605 decreased radiation-induced, MPO-dependent ACS. Protein tyrosine phosphatase (PTP) and protein serine/threonine phosphatase (PSTP) inhibitors decreased the radiation-induced increase in ACS. Peroxidase cycle results demonstrate that tyrosine phosphorylation blocks MPO Compound I formation by preventing catalysis on H2O2 in the active site of MPO. EPR data demonstrate that γ-radiation increased tyrosyl radical species formation in a dose-dependent manner. CONCLUSIONS: We demonstrate that γ-radiation induces MPO-dependent generation of ACS, which is dependent, at least in part, by protein tyrosine and Ser/Thr dephosphorylation and is reduced by LGM2605. This study identified for the first time a novel protein dephosphorylation-dependent mechanism of radiation-induced MPO activation.

Evaluation of Xpert MTB/RIF Assay for Diagnosis of Tuberculosis in Children.

Introduction: Childhood tuberculosis (TB) is now a global priority. With the advent of Xpert MTB/RIF, more TB cases in children are being reported. This study was undertaken to evaluate the performance of Xpert in diagnosis of pulmonary and extra-pulmonary TB in children. Methods: Specimens from 171 suspected TB cases in children aged <15 years were tested with Xpert, culture and smear microscopy in the Department of Microbiology, Institute of Medical Sciences, India. Results: The specimens included 106 gastric aspirates, 51 cerebrospinal fluids, 8 induced sputum and 6 lymph node aspirates. Xpert detected Mycobacterium tuberculosis in 19 cases (14 pulmonary and 5 extra-pulmonary), 7 of which were rifampicin-resistant. Sensitivity, specificity, positive predictive value and negative predictive value of Xpert compared with culture were 88.89, 98.04, 84.21 and 98.68%, respectively. The sensitivity was 100% in children aged 1-5 years and 6-10 years and in gastric aspirates. Conclusion: Xpert is an efficient diagnostic tool in childhood tuberculosis.