An update on COVID-19 in paediatric and young adults with nephrotic syndrome, receiving chronic immunosuppression during the Omicron pandemic.
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ABSTRACT:
SUBMITTER: Angeletti A
PROVIDER: S-EPMC8993668 | biostudies-literature |
REPOSITORIES: biostudies-literature
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| S-EPMC7536764 | 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: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:ObjectiveTo update and extend our previous systematic review on first- (FGAs) and second-generation antipsychotics (SGAs) for treatment of psychiatric and behavioral conditions in children, adolescents, and young adults (aged ≤24 years). This article focuses on the evidence for harms.MethodWe searched (to April 2016) 8 databases, gray literature, trial registries, Food and Drug Administration reports, and reference lists. Two reviewers conducted study screening and selection independently, with consensus for selection. One reviewer extracted and another verified all data; 2 reviewers independently assessed risk of bias. We conducted meta-analyses when appropriate and network meta-analysis across conditions for changes in body composition. Two reviewers reached consensus for ratings on the strength of evidence for prespecified outcomes.ResultsA total of 135 studies (95 trials and 40 observational) were included, and 126 reported on harms. FGAs caused slightly less weight gain and more extrapyramidal symptoms than SGAs. SGAs as a class caused adverse effects, including weight gain, high triglyceride levels, extrapyramidal symptoms, sedation, and somnolence. They appeared to increase the risk for high cholesterol levels and type 2 diabetes. Many outcomes for individual drug comparisons were of low or insufficient strength of evidence. Olanzapine caused more short-term gains in weight and body mass index than several other SGAs. The dose of SGAs may not make a difference over the short term for some outcomes.ConclusionsClinicians need to weigh carefully the benefit-to-harm ratio when using antipsychotics, especially when treatment alternatives exist. More evidence is needed on the comparative harms between antipsychotics over the longer term.
| S-EPMC6187435 | biostudies-literature
Project description:The objective of this study was to characterize multiple chronic conditions (MCCs) among seriously ill adults receiving palliative care at the end of life. A latent class analysis was conducted to identify latent subgroups of seriously ill older adults based on a baseline Charlson comorbidity index (CCI) measurement, a measure of comorbidity burden, and mortality risk. The three latent subgroups were: (1) low to moderate CCI with MCC, (2) high CCI with MCC, and (3) high CCI and metastatic cancer. The "low to moderate CCI and MCC" subgroup included older adults with chronic obstructive pulmonary disease (COPD), cardiovascular disease, congestive heart failure, myocardial infarction, dementia, diabetes, and lymphoma. A "high CCI and MCC" subgroup included individuals with severe illness including liver or renal disease among other MCCs. A "high CCI and metastatic cancer" included all participants with metastatic cancer. This study sheds light on the MCC profile of seriously ill adults receiving palliative care.
| S-EPMC9040129 | biostudies-literature
Project description:BackgroundThe 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.MethodsNinety-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.ResultsEighteen 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.ConclusionOur 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:Background and objectivesYoung adults receiving kidney replacement therapy (KRT) have impaired quality of life and may exhibit low medication adherence. We tested the hypothesis that wellbeing and medication adherence are associated with psychosocial factors.Design, setting, participants, & measurementsWe conducted a cross-sectional online survey for young adults on KRT. Additional clinical information was obtained from the UK Renal Registry. We compared outcomes by treatment modality using age- and sex-adjusted regression models, having applied survey weights to account for response bias by sex, ethnicity, and socioeconomic status. We used multivariable linear regression to examine psychosocial associations with scores on the Warwick-Edinburgh Mental Wellbeing Scale and the eight-item Morisky Medication Adherence Scale.ResultsWe recruited 976 young adults and 64% responded to the survey; 417 (71%) with transplants and 173 (29%) on dialysis. Wellbeing was positively associated with extraversion, openness, independence, and social support, and negatively associated with neuroticism, negative body image, stigma, psychologic morbidity, and dialysis. Higher medication adherence was associated with living with parents, conscientiousness, physician access satisfaction, patient activation, age, and male sex, and lower adherence was associated with comorbidity, dialysis, education, ethnicity, and psychologic morbidity.ConclusionsWellbeing and medication adherence were both associated with psychologic morbidity in young adults. Dialysis treatment is associated with poorer wellbeing and medication adherence.
| S-EPMC6237074 | 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:Patients with chronic inflammatory diseases (CID) experience accelerated loss of bone mineral density, which is often accompanied by increased vascular calcification. These disturbances can be attenuated by therapies for inflammation, such as the tumor necrosis factor inhibitor infliximab. Calciprotein particles (CPP) are circulating colloidal aggregates of calcium and phosphate together with the mineral-binding protein fetuin-A, which have emerged as potential mediators of vascular calcification. The precise origins of serum CPP are unclear, but bone turnover may be an important source. In this longitudinal observational study, we studied patients with CID undergoing treatment with infliximab to assess the temporal relationship between bone turnover and circulating CPP. Ten patients with active CID receiving infliximab induction therapy and an additional 3 patients with quiescent CID on maintenance infliximab therapy were studied for 8 weeks with repeated measures of bone turnover markers as well as CPP (calciprotein monomers [CPM], primary CPP [CPP-I], and secondary CPP [CPP-II]). Therapeutic response was appraised using validated disease activity scores. At baseline, those with active CID had elevated markers of bone resorption and suppressed bone formation markers as well as higher CPM and CPP-I compared with those with quiescent CID. In responders, there was an early but transient reduction in resorption markers by week 1, but a more sustained increase in bone formation markers compared with non-responders at week 8. This was accompanied by reductions in CPM (β = -6.5 × 103 AU [95% CI -11.1, -1.8], p = 0.006) and CPP-I (β = -23.4 × 104 particles/mL [95% CI -34.8, -11.9], p < 0.001). In contrast, no significant changes in any markers were observed in non-responders or those receiving maintenance therapy. Thus, CPP have a dynamic association with changes in bone turnover in response to infliximab therapy, adding to accumulating evidence of the role of bone as a determinant of systemic levels. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
| S-EPMC8216135 | biostudies-literature