An update on COVID-19 in paediatric and young adults with nephrotic syndrome, receiving chronic immunosuppression during the Omicron pandemic.
Ontology highlight
ABSTRACT:
SUBMITTER: Angeletti A
PROVIDER: S-EPMC8993668 | biostudies-literature | 2022 Jul
REPOSITORIES: biostudies-literature
Publications
An update on COVID-19 in paediatric and young adults with nephrotic syndrome, receiving chronic immunosuppression during the Omicron pandemic.
Angeletti Andrea A Bruschi Maurizio M Bigatti Carolina C Palmeri Serena S Lugani Francesca F Verrina Enrico E Ghiggeri Gian Marco GM
Journal of nephrology 20220409 6
Similar Datasets
Project description: Not available
| S-EPMC7536764 | biostudies-literature
Project description:Advances in genome science in the last 20 years have led to the discovery of over 50 single gene causes and genetic risk loci for steroid resistant nephrotic syndrome (SRNS). Despite these advances, the genetic architecture of childhood steroid sensitive nephrotic syndrome (SSNS) remains poorly understood due in large part to the varying clinical course of SSNS over time. Recent exome and genome wide association studies from well-defined cohorts of children with SSNS identified variants in multiple MHC class II molecules such as HLA-DQA1 and HLA-DQB1 as risk factors for SSNS, thus stressing the central role of adaptive immunity in the pathogenesis of SSNS. However, evidence suggests that unknown second hit risk loci outside of the MHC locus and environmental factors also make significant contributions to disease. In this review, we examine what is currently known about the genetics of SSNS, the implications of recent findings on our understanding of pathogenesis of SSNS, and how we can utilize these results and findings from future studies to improve the management of children with nephrotic syndrome.
| S-EPMC6361778 | biostudies-literature
Project description:In children, sporadic nephrotic syndrome can be related to a genetic cause, but to what extent genetic alterations associate with resistance to immunosuppression is unknown. In this study, we designed a custom array for next-generation sequencing analysis of 19 target genes, reported as possible causes of nephrotic syndrome, in a cohort of 31 children affected by sporadic steroid-resistant nephrotic syndrome and 38 patients who exhibited a similar but steroid-sensitive clinical phenotype. Patients who exhibited extrarenal symptoms, had a familial history of the disease or consanguinity, or had a congenital onset were excluded. We identified a genetic cause in 32.3% of the children with steroid-resistant disease but zero of 38 children with steroid-sensitive disease. Genetic alterations also associated with lack of response to immunosuppressive agents in children with steroid-resistant disease (0% of patients with alterations versus 57.9% of patients without alterations responded to immunosuppressive agents), whereas clinical features, age at onset, and pathologic findings were similar in steroid-resistant patients with and without alterations. These results suggest that heterogeneous genetic alterations in children with sporadic forms of nephrotic syndrome associate with resistance to steroids as well as immunosuppressive treatments. In these patients, a comprehensive screening using such an array may, thus, be useful for genetic counseling and may help clinical decision making in a fast and cost-efficient manner.
| S-EPMC4279734 | biostudies-literature
Project description:The aim of the current PodoNet registry analysis was to evaluate the outcome of steroid-resistant nephrotic syndrome (SRNS) in children who were not treated with intensified immunosuppression (IIS), focusing on the potential for spontaneous remission and the role of angiotensin blockade on proteinuria reduction. Ninety-five pediatric patients who did not receive any IIS were identified in the PodoNet Registry. Competing risk analyses were performed on 67 patients with nephrotic-range proteinuria at disease onset to explore the cumulative rates of complete or partial remission or progression to kidney failure, stratified by underlying etiology (genetic vs. non-genetic SRNS). In addition, Cox proportional hazard analysis was performed to identify factors predicting proteinuria remission. Eighteen of 31 (58.1%) patients with non-genetic SRNS achieved complete remission without IIS, with a cumulative likelihood of 46.2% at 1 year and 57.7% at 2 years. Remission was sustained in 11 children, and only two progressed to kidney failure. In the genetic subgroup (n = 27), complete resolution of proteinuria occurred very rarely and was never sustained; 6 (21.7%) children progressed to kidney failure at 3 years. Almost all children (96.8%) received proteinuria-lowering renin-angiotensin-aldosterone system (RAAS) antagonist treatment. On antiproteinuric treatment, partial remission was achieved in 7 of 31 (22.6%) children with non-genetic SRNS and 9 of 27 children (33.3%) with genetic SRNS. Our results demonstrate that spontaneous complete remission can occur in a substantial fraction of children with non-genetic SRNS and milder clinical phenotype. RAAS blockade increases the likelihood of partial remission of proteinuria in all forms of SRNS. A higher resolution version of the Graphical abstract is available as Supplementary information.
| S-EPMC10060323 | biostudies-literature
Project description: Not available
| S-EPMC6077169 | biostudies-literature
Project description:Background and objectivesIntensified immunosuppression in steroid-resistant nephrotic syndrome is broadly applied, with disparate outcomes. This review of patients from the United Kingdom National Study of Nephrotic Syndrome cohort aimed to improve disease stratification by determining, in comprehensively genetically screened patients with steroid-resistant nephrotic syndrome, if there is an association between response to initial intensified immunosuppression and disease progression and/or post-transplant recurrence.Design, setting, participants, & measurementsPediatric patients with steroid-resistant nephrotic syndrome were recruited via the UK National Registry of Rare Kidney Diseases. All patients were whole-genome sequenced, whole-exome sequenced, or steroid-resistant nephrotic syndrome gene-panel sequenced. Complete response or partial response within 6 months of starting intensified immunosuppression was ascertained using laboratory data. Response to intensified immunosuppression and outcomes were analyzed according to genetic testing results, pattern of steroid resistance, and first biopsy findings.ResultsOf 271 patients, 178 (92 males, median onset age 4.7 years) received intensified immunosuppression with response available. A total of 4% of patients with monogenic disease showed complete response, compared with 25% of genetic-testing-negative patients (P=0.02). None of the former recurred post-transplantation. In genetic-testing-negative patients, 97% with complete response to first intensified immunosuppression did not progress, whereas 44% of nonresponders developed kidney failure with 73% recurrence post-transplant. Secondary steroid resistance had a higher complete response rate than primary/presumed resistance (43% versus 23%; P=0.001). The highest complete response rate in secondary steroid resistance was to rituximab (64%). Biopsy results showed no correlation with intensified immunosuppression response or outcome.ConclusionsPatients with monogenic steroid-resistant nephrotic syndrome had a poor therapeutic response and no post-transplant recurrence. In genetic-testing-negative patients, there was an association between response to first intensified immunosuppression and long-term outcome. Patients with complete response rarely progressed to kidney failure, whereas nonresponders had poor kidney survival and a high post-transplant recurrence rate. Patients with secondary steroid resistance were more likely to respond, particularly to rituximab.
| S-EPMC7341765 | biostudies-literature
Project description:BackgroundNephrotic syndrome (NS) is a renal disease characterized by excessive proteinuria (greater than 3.5 g/dl per 24 h), which results in hypoalbuminemia and leads to hyperlipidemia, edema, and various complications. NS patients typically respond to standard steroid treatment (prednisolone) and are classified as having steroid-sensitive nephrotic syndrome (SSNS). However, patients who do not respond to steroid therapy after 4 weeks are referred to as having steroid-resistant nephrotic syndrome (SRNS). The unequal response to steroid treatment in nephrotic syndrome involved many factors, including genetic, medication, and kidney diseases. The CYP3A gene family is predominantly involved in the metabolism of medications used in the treatment of NS.MethodologyA systematic literature review was conducted from January 2014 to June 2024 using an extensive electronic search of data related to pediatric nephrotic syndrome and the CYP gene family, including associated polymorphisms. Through this review, we systematically analyze factors that affect the metabolism of medications targeting the CYP3A gene family (including steroidal and non-steroidal drugs) commonly used in the treatment of NS and its comorbidities.ConclusionStudies have correlated the relationship between polymorphisms in the CYP3A gene family and medication in NS, with 90 % of the research focusing primarily on post-kidney transplant NS patients. Many studies have reported a correlation between CYP3A gene family polymorphisms and increased tacrolimus (TAC) dosage.
| S-EPMC11800309 | biostudies-literature
Project description:Genetic testing in nephrotic syndrome may identify heterozygous predicted-pathogenic variants (HPPVs) in autosomal recessive (AR) genes that are known to cause disease in the homozygous or compound heterozygous state. In such cases, it can be difficult to define the variant's true significance and questions remain about whether a second pathogenic variant has been missed during analysis or whether the variant is an incidental finding. There are now known to be over 70 genes associated with nephrotic syndrome, the majority inherited as an AR trait. Knowledge of whether such HPPVs occur with equal frequency in patients compared to the general population would assist interpretation of their significance. Exome sequencing was performed on 187 Steroid-Resistant Nephrotic Syndrome (SRNS) paediatric patients recruited to a UK rare disease registry plus originating from clinics at Evelina, London. 59 AR podocytopathy linked genes were analysed in each patient and a list of HPPVs created. We compared the frequency of detected HPPVs with a 'control' population from the gnomAD database containing exome data from approximately 50,000 individuals. A bespoke filtering process was used for both patients and controls to predict 'likely pathogenicity' of variants. In total 130 Caucasian SRNS patients were screened across 59 AR genes and 201 rare heterozygous variants were identified. 17/201 (8.5%) were assigned as 'likely pathogenic' (HPPV) using our bespoke filtering method. Comparing each gene in turn, for SRNS patients with a confirmed genetic diagnosis, in 57 of the 59 genes we found no statistically significant difference in the frequency of these HPPVs between patients and controls (In genes ARHGDIA and TP53RK, we identified a significantly higher number of HPPVs in the control population compared with the patients when filtering was performed with 'high stringency' settings only). In the SRNS patients without a genetics diagnosis confirmed, there was no statistically significant difference identified in any gene between patient and control. In children with SRNS, we propose that identification of HPPV in AR podocytopathy linked genes is not necessarily representative of pathogenicity, given that the frequency is similar to that seen in controls for the majority. Whilst this may not exclude the presence of genetic kidney disease, this type of heterozygous variant is unlikely to be causal and each result must be interpreted in its clinical context.
| S-EPMC11316802 | biostudies-literature
Project description:ObjectiveTo study the risk of acquiring Corona Virus Disease 2019 (COVID-19) and its outcomes in patients on immunosuppressive therapy (IST) for chronic autoimmune neuromuscular disorders (aNMD) and multiple sclerosis (MS).MethodsWe used TriNetX, a global health collaborative clinical research platform collecting real-time electronic medical records data, which has one of the largest known global COVID-19 database. We included patients with chronic autoimmune neuromuscular disorders (aNMD) [myasthenia gravis (MG), inflammatory myositis, and chronic inflammatory neuropathies (CIN)] and MS, based on the International Classification of Disease-10 (ICD-10) coding for one year before January 20th, 2020. We examined the use of IST, rate of COVID- 19, hospitalization, intubation, and mortality among the patients with aNMD and MS.ResultsA total of 33,451 patients with aNMD and 42,899 patients with MS were included. Among them, 111 (0.33%) patients with aNMD and 115 patients (0.27%) with MS had COVID-19. About one third of them required hospitalization. IST did not appear to have a significant impact on overall infection risk in either group; however, risk of hospitalization for immunosuppressed patients with aNMD was higher (Odds ratio 2.86, p-value 0.011).ConclusionsIST use does not appear to make patients with aNMD and MS more vulnerable to COVID-19. IST may be continued during the pandemic, as previously suggested by expert opinion guidelines. However, it is important to consider individualizing immunotherapy regimens in some cases. Additional physician reported registry-based data is needed to further confirm these findings.
| S-EPMC7837234 | biostudies-literature
Project description:Congenital nephrotic syndrome (CNS) is a rare kidney disorder characterized by heavy proteinuria, hypoproteinemia, and edema starting soon after birth. The majority of cases are caused by genetic defects in the components of the glomerular filtration barrier, especially nephrin and podocin. CNS may also be a part of a more generalized syndrome or caused by a perinatal infection. Immunosuppressive medication is not helpful in the genetic forms of CNS, and kidney transplantation is the only curative therapy. Before the operation, management of these infants largely depends on the magnitude of proteinuria. In severe cases, daily albumin infusions are required to prevent life-threatening edema. The therapy also includes hypercaloric diet, thyroxin and mineral substitution, prevention of thrombotic episodes, and prompt management of infectious complications. The outcome of CNS patients without major extrarenal manifestations is comparable with other patient groups after kidney transplantation.
| S-EPMC2753773 | biostudies-other