Refractory Minimal Change Disease and Focal Segmental Glomerular Sclerosis Treated With Anakinra.
Ontology highlight
ABSTRACT:
SUBMITTER: Angeletti A
PROVIDER: S-EPMC8720665 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:This study will investigate if urine metabolomics can help understand the pathophysiology of glomerular diseases.
2015-02-12 | ST000329 | MetabolomicsWorkbench
Project description:Rituximab (RTX) may benefit patients with glomerular disease who suffer from focal segmental glomerular sclerosis (FSGS) or minimal change disease (MCD). Here, we have described our experience treating 6 FSGS and 9 MCD patients with steroid-dependent/refractory nephrotic syndrome (NS) with RTX. Patients received RTX (375 mg/m2) intravenously on days 1, 8, 23, and 29. During a median follow-up of 8 months (range, 3-36 months) after RTX administration, all patients achieved complete or partial remission. Relapses decreased by approximately 30-fold compared with the year preceding RTX treatment, and an 89.27% reduction in proteinuria was observed. Furthermore, RTX treatment could decrease medical costs by 76.52% compared with the costs associated with the long-term use (for 12-13 months) of steroids and immunosuppressive drugs. In conclusion, RTX treatment was safe and effective for patients with refractory FSGS or MCD.
| S-EPMC5706808 | biostudies-literature
Project description:ObjectiveTo search for biomarkers to differentiate primary focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD).MethodsWe isolated glomeruli from kidney biopsies of 6 patients with adult-onset steroid sensitiveFSGS and 5 patients with MCD, and compared the profiles of glomerular transcriptomes between the two groups of patients using microarray analysis.ResultsAnalysis of differential expressed genes (DEGs) revealed that up-regulated DEGs in FSGS patients compared with MCD patients were primarily involved in spermatogenesis, gamete generation, regulation of muscle contraction, response to unfolded protein, cell proliferation and skeletal system development. The down-regulated DEGs were primarily related to metabolic process, intracellular transport, oxidation/reduction andestablishment of intracellular localization. We validated the expression of the top 6 up-regulated and top 6 down-regulated DEGs using real-time PCR. Membrane metallo-endopeptidase (MME) is a down-regulated gene that was previously identified as a key gene for kidney development. Immunostaining confirmed that the protein expression of MME decreased significantly in FSGS kidneys compared with MCD kidneys.ConclusionsThis report was the first study to examine transcriptomes in Chinese patients with various glomerular diseases. Expressions of MME both in RNA and protein level decreased significantly in glomeruli of FSGS kidneys compared with MCD kidneys. Our data suggested that MME might play a role in the normal physiological function of podocytes and a decrease in MME expression might be related to podocyte injury. We also identified genes and pathways specific for FSGS versus MCD, and our data could help identify potential new biomarkers for the differential diagnosis between these two diseases.
| S-EPMC4633097 | biostudies-literature
Project description:To search for biomarkers to differentiate Adult-Onset Steroid Sensitive focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD).
2017-01-04 | GSE69814 | GEO
Project description:To search for biomarkers to differentiate Adult-Onset Steroid Sensitive focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD). Compared the profiles of glomerular transcriptomes between patients with FSGS and patients with MCD using microarray analysis. This dataset is part of the TransQST collection.
2017-01-04 | E-GEOD-69814 | biostudies-arrayexpress
Project description:Rationale & objectiveAssessment of how patients feel and function is needed for clinical care and research for focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD). The objective of this study was to develop a patient-reported outcome assessment appropriate for use in children and adults with FSGS and MCD.Study designQualitative study using semi-structured interviews.Setting & participants48 semi-structured interviews with children aged 8 to 17 years (n = 11) and adults (n = 10) with FSGS and children aged 8 to 17 (n = 11) and adults (n = 16) with MCD recruited from 3 academic medical centers.Analytical approachLatent content analysis.ResultsFSGS and MCD have a pervasive and comparable impact on physical, social, and mental health-related quality of life regardless of age or diagnosis. Physical symptoms of swelling, fatigue, and pain were articulated by most participants. Disease management was also a frequent topic of discussion; participants described their experiences with medication and associated side effects, as well as lifestyle changes made to manage their disease (ie, dietary changes and frequent medical appointments). These discussions often identified a profound impact on physical abilities and life participation. In many instances, participants described the negative impact these symptoms had on their mood and sense of self, with most participants reporting feelings of anxiety.LimitationsParticipants were primarily non-Hispanic White and English speaking, which may limit generalizability.ConclusionsOur results suggest that there are commonalities to the FSGS-MCD patient experience of health-related quality of life that will enable the generation of a disease-specific FSGS-MCD patient-reported outcomes instrument for use in children and adults. The development of this tool is intended to facilitate better care and support clinical research for these individuals.
| S-EPMC8350833 | biostudies-literature
Project description:This study will investigate if urine metabolomics can help understand the pathophysiology of glomerular diseases.
2018-08-02 | MSV000082711 | GNPS
Project description:Minimal change disease (MCD) and primary focal segmental glomerulosclerosis (FSGS) are glomerular diseases characterized by nephrotic syndrome. Their diagnosis requires a renal biopsy, but it is an invasive procedure with potential complications. In a small biopsy sample, where only normal glomeruli are observed, FSGS cannot be differentiated from MCD. The correct diagnosis is crucial to an effective treatment, as MCD is normally responsive to steroid therapy, whereas FSGS is usually resistant. The purpose of our study was to discover and validate novel early urinary biomarkers capable to differentiate between MCD and FSGS.Forty-nine patients biopsy-diagnosed of MCD and primary FSGS were randomly subdivided into a training set (10 MCD, 11 FSGS) and a validation set (14 MCD, 14 FSGS). The urinary proteome of the training set was analyzed by two-dimensional differential gel electrophoresis coupled with mass spectrometry. The proteins identified were quantified by enzyme-linked immunosorbent assay in urine samples from the validation set.Urinary concentration of alpha-1 antitrypsin, transferrin, histatin-3 and 39S ribosomal protein L17 was decreased and calretinin was increased in FSGS compared to MCD. These proteins were used to build a decision tree capable to predict patient's pathology.This preliminary study suggests a group of urinary proteins as possible non-invasive biomarkers with potential value in the differential diagnosis of MCD and FSGS. These biomarkers would reduce the number of misdiagnoses, avoiding unnecessary or inadequate treatments.
| S-EPMC5291957 | biostudies-literature
Project description:Background: Minimal change disease (MCD) and focal-segmental glomerulosclerosis (FSGS) are immune-mediated glomerular diseases manifesting as nephrotic syndrome. Autoantibodies against the podocyte slit diaphragm protein nephrin were recently identified in a subset of patients with minimal change disease, but their clinical and pathophysiological significance is largely unknown. Methods: Using immunoprecipitation assays, we performed a blinded screening for anti-nephrin antibodies in diagnostic and follow-up serum samples from adult patients with biopsy-proven MCD, FSGS, IgA nephropathy, and membranous nephropathy in comparison to healthy controls in two independent patient cohorts from Hamburg, Germany, and Bari, Italy. We further established a mouse model of anti-nephrin antibody-induced disease by active immunization using the recombinant murine nephrin ectodomain. Results: Anti-nephrin autoantibodies were detected in 50 of 110 (45%) patients with MCD, 8 of 107 (7%) patients with FSGS, 1 of 50 (2%) patients with membranous nephropathy, 0 of 48 (0%) patients with IgA nephropathy, and 0 of 67 (0%) healthy individuals. During follow-up, presence, and absence of anti-nephrin autoantibodies in patients with MCD and FSGS strongly correlated with active disease and remission, respectively. Immunization of mice induced anti-nephrin autoantibody formation and a highly dynamic phenotype with severe nephrotic syndrome and the histological features of MCD. Mechanistically, anti-nephrin autoantibodies induced nephrin phosphorylation at Tyr1191, cytoskeletal rearrangement, and downregulation of key podocyte proteins. Conclusion: Anti-nephrin antibodies are a valuable biomarker of disease activity in patients with MCD and FSGS, and binding of anti-nephrin antibodies at the podocyte slit diaphragm induces MCD with nephrotic syndrome.
2024-05-27 | PXD047417 | Pride
Project description:BackgroundMinimal change disease (MCD) and primary focal segmental glomerulosclerosis (FSGS) are the main causes of primary idiopathic nephrotic syndrome in children and adults, with diagnosis being essential for the appropriate choice of therapy and requiring renal biopsy. However, the presence of only normal glomeruli on renal biopsy of FSGS patients may lead to the misclassification of these patients as having MCD. The aim of this study was to (i) compare the peptide profile of MCD and FSGS patients with that of a group of healthy subjects, (ii) generate and validate a class prediction model to classify MCD and FSGS patients and (ii) identify candidate biomarkers of these glomerular entities by analysis of the urinary peptidome.MethodsThe urinary peptide profile was analyzed by magnetic bead-based technology combined with MALDI-TOF mass spectrometry in 44 patients diagnosed of MCD (n = 22) and FSGS (n = 22). The resulting spectra were compiled and analyzed using ClinProTools software.ResultsA class prediction model was developed to differentiate MCD and FSGS patients. The validation of this model correctly classified 81.8% (9/11) of MCD patients and 72.7% (8/11) of FSGS patients. Moreover, the signal with m/z 1913.60, identified as a fragment of uromodulin, and the signal with m/z 2392.54, identified as a fragment of alpha-1-antitrypsin, showed higher and lower peak areas, respectively, in FSGS patients compared with MCD patients.ConclusionsThe simple, non-invasive technique described in the present study may be a useful tool to help clinicians by confirming diagnoses achieved by renal biopsy, thereby reducing misdiagnoses and avoiding the implementation of inappropriate therapies.
| S-EPMC3907468 | biostudies-literature