33 research outputs found
MEFV mutations in systemic JIA
Background: Systemic form of juvenile idiopathic arthritis (JIA) is regarded as an autoinflammatory disease. Certain genetic polymorphisms in genes coding inflammatory proteins have been associated with the disease. On the other hand mutations of the MEFV gene cause a monogenic autoinflammatory disease, Familial Mediterranean Fever (FMF).
In a previous study in adult rheumatoid arthritis 3 out of the 25 British patients who developed secondary amyloidosis had a mutation/polymorphism in the MEFV gene.
Aim: To analyse whether mutaions in the MEFV gene had an association with systemic JIA.
Patients and methods: MEFV mutations were screened in a total of 32 systemic JIA patients. All had been classified as systemic JIA according to the Durban JIA criteria. None had disease characteristics that met the Tel Hashomer criteria for the diagnosis of FMF.
Results: 2 carrier for M694V and two patients who were homozygote for MEFV mutations. Both of these patients were among the most severe patients in the group. One had an excellent response to etanercept whereas the other was resistant to anti-TNF and other conventional treatments and had only a partial response to thalidomide. Although the number of severe mutations were increased in this small group of patients with systemic JIA the difference with the Turkish population did not reach statistical significance, but the disease causing mutation (M694V) was significantly high in the patients with systemic JIA(p = 0.02).
Conclusion: However, the severe disease course in the aforementioned patients suggest that MEFV mutations may be a modifying genetic factor in systemic JIA.PubMe
Does unity of Familial Mediterranean fever with juvenile idiopathic arthritis affect the outcome?
PubMe
Pres-Final-2218: Treatment Of Colchicines Resistant Fmf: Experience Of A Pediatric Center In Turkey
PubMe
Methylenetetrahydrfolate reductase gene A1298C polymorphism does not reflect the efficacy of methotrexate in Juvenile Idiopathic Arthritis
Erratum to: Risk factors for progression in children and young adults with IgA nephropathy: an analysis of 261 cases from the VALIGA European cohort.
Item does not contain fulltex
Quantifying duration of proteinuria remission and association with clinical outcome in IgA nephropathy
Background On the basis of findings of observational studies and a meta-analysis, proteinuria reduction has been proposed as a surrogate outcome in IgA nephropathy. How long a reduction in proteinuria needs to be maintained to mitigate the long-term risk of disease progression is unknown. Methods In this retrospective multiethnic cohort of adult patients with IgA nephropathy, we defined proteinuria remission as a $25% reduction in proteinuria from the peak value after biopsy, and an absolute reduction in proteinuria to,1 g/d. The exposure of interest was the total duration of first remission, treated as a time-varying covariate using longitudinal proteinuria measurements. We used time-dependent Cox proportional hazards regression models to quantify the association between the duration of remission and the primary outcome (ESKD or a 50% reduction in eGFR). Results During a median follow-up of 3.9 years, 274 of 1864 patients (14.7%) experienced the primary outcome. The relationship between duration of proteinuria remission and outcome was nonlinear. Each 3 months in sustained remission up to approximately 4 years was associated with an additional 9% reduction in the risk of disease progression (hazard ratio [HR], 0.91; 95% confidence interval [95% CI], 0.89 to 0.93). Thereafter, each additional 3 months in remission was associated with a smaller, nonsignificant risk reduction (HR, 0.99; 95% CI, 0.96 to 1.03). These findings were robust to multivariable adjustment and consistent across clinical and histologic subgroups. Conclusions Our findings support the use of proteinuria as a surrogate outcome in IgA nephropathy, but additionally demonstrate the value of quantifying the duration of proteinuria remission when estimating the risk of hard clinical endpoints. Copyright © 2021 by the American Society of Nephrology
Evaluating a New International Risk-Prediction Tool in IgA Nephropathy
ImportanceAlthough IgA nephropathy (IgAN) is the most common
glomerulonephritis in the world, there is no validated tool to predict
disease progression. This limits patient-specific risk stratification
and treatment decisions, clinical trial recruitment, and biomarker
validation. ObjectiveTo derive and externally validate a prediction
model for disease progression in IgAN that can be applied at the time of
kidney biopsy in multiple ethnic groups worldwide. Design, Setting, and
ParticipantsWe derived and externally validated a prediction model using
clinical and histologic risk factors that are readily available in
clinical practice. Large, multi-ethnic cohorts of adults with
biopsy-proven IgAN were included from Europe, North America, China, and
Japan. Main Outcomes and MeasuresCox proportional hazards models were
used to analyze the risk of a 50% decline in estimated glomerular
filtration rate (eGFR) or end-stage kidney disease, and were evaluated
using the R-D(2) measure, Akaike information criterion (AIC), C
statistic, continuous net reclassification improvement (NRI), integrated
discrimination improvement (IDI), and calibration plots. ResultsThe
study included 3927 patients; mean age, 35.4 (interquartile range,
28.0-45.4) years; and 2173 (55.3%) were men. The following prediction
models were created in a derivation cohort of 2781 patients: a clinical
model that included eGFR, blood pressure, and proteinuria at biopsy; and
2 full models that also contained the MEST histologic score, age,
medication use, and either racial/ethnic characteristics (white,
Japanese, or Chinese) or no racial/ethnic characteristics, to allow
application in other ethnic groups. Compared with the clinical model,
the full models with and without race/ethnicity had better R-D(2)
(26.3% and 25.3%, respectively, vs 20.3%) and AIC (6338 and 6379,
respectively, vs 6485), significant increases in C statistic from 0.78
to 0.82 and 0.81, respectively (Delta C, 0.04; 95% CI, 0.03-0.04 and
Delta C, 0.03; 95% CI, 0.02-0.03, respectively), and significant
improvement in reclassification as assessed by the NRI (0.18; 95% CI,
0.07-0.29 and 0.51; 95% CI, 0.39-0.62, respectively) and IDI (0.07;
95% CI, 0.06-0.08 and 0.06; 95% CI, 0.05-0.06, respectively). External
validation was performed in a cohort of 1146 patients. For both full
models, the C statistics (0.82; 95% CI, 0.81-0.83 with race/ethnicity;
0.81; 95% CI, 0.80-0.82 without race/ethnicity) and R-D(2) (both
35.3%) were similar or better than in the validation cohort, with
excellent calibration. Conclusions and RelevanceIn this study, the 2
full prediction models were shown to be accurate and validated methods
for predicting disease progression and patient risk stratification in
IgAN in multi-ethnic cohorts, with additional applications to clinical
trial design and biomarker research