16 research outputs found
Galaxy Formation: Was There A Big Bang Shell?
The tight correlation of galactic velocity distribution to both luminosity
and its black hole mass and the relation of halo parameters to luminous mass
distribution, can not be due to collapse dynamics. A big bang shell can solve
galaxy formation problems by forming the supermassive black holes necessary to
capture the initial blast wave in a coordinated pattern.Comment: 7 pages late
Tonsillectomy in a European Cohort of 1,147 Patients with IgA Nephropathy
BACKGROUND:
Tonsillectomy has been considered a treatment for IgA nephropathy (IgAN). It is aimed at removing a source of pathogens, reducing mucosa-associated lymphoid tissue and decreasing polymeric IgA synthesis. However, its beneficial effect is still controversial. In Asia, favorable outcomes have been claimed mostly in association with corticosteroids. In Europe, small, single-center uncontrolled studies have failed to show benefits.
METHODS:
The European validation study of the Oxford classification of IgAN (VALIGA) collected data from 1,147 patients with IgAN over a follow-up of 4.7 years. We investigated the outcome of progression to end-stage renal disease (ESRD) and/or 50% loss of estimated glomerular filtration rate (eGFR) and the annual loss of eGFR in 61 patients who had had tonsillectomy.
RESULTS:
Using the propensity score, which is a logistic regression model, we paired 41 patients with tonsillectomy and 41 without tonsillectomy with similar risk of progression (gender, age, race, mean blood pressure, proteinuria, eGFR at renal biopsy, previous treatments and Oxford MEST scores). No significant difference was found in the outcome. Moreover, we performed an additional propensity score pairing 17 patients who underwent tonsillectomy after the diagnosis of IgAN and 51 without tonsillectomy with similar risk of progression at renal biopsy and subsequent treatments. No significant difference was found in changes in proteinuria, or in the renal end point of 50% reduction in GFR and/or ESRD, or in the annual loss of eGFR.
CONCLUSION:
In the large VALIGA cohort of European subjects with IgAN, no significant correlation was found between tonsillectomy and renal function decline. © 2015 S. Karger AG, Basel
Improving treatment decisions using personalized risk assessment from the International IgA Nephropathy Prediction Tool
Immunosuppression in IgA nephropathy (IgAN) should be reserved for patients at high-risk of disease progression, which KDIGO guidelines determine based solely on proteinuria 1g or more/day. To investigate if treatment decisions can be more accurately accomplished using individualized risk from the International IgAN Prediction Tool, we simulated allocation of a hypothetical immunosuppression therapy in an international cohort of adults with IgAN. Two decision rules for treatment were applied based on proteinuria of 1g or more/day or predicted risk from the Prediction Tool above a threshold probability. An appropriate decision was defined as immunosuppression allocated to patients experiencing the primary outcome (50% decline in eGFR or ESKD) and withheld otherwise. The net benefit and net reduction in treatment are the proportion of patients appropriately allocated to receive or withhold immunosuppression, adjusted for the harm from inappropriate decisions, calculated for all threshold probabilities from 0-100%. Of 3299 patients followed for 5.1 years, 522 (15.8%) experienced the primary outcome. Treatment allocation based solely on proteinuria of 1g or more/day had a negative net benefit (was harmful) because immunosuppression was increasingly allocated to patients without progressive disease. Compared to using proteinuria, treatment allocation using the Prediction Tool had a larger net benefit up to 23.4% (95% confidence interval 21.5-25.2%) and a larger net reduction in treatment up to 35.1% (32.3-37.8%). Thus, allocation of immunosuppression to high-risk patients with IgAN can be substantially improved using the Prediction Tool compared to using proteinuria
Is there long-term value of pathology scoring in immunoglobulin A nephropathy?: A validation study of the Oxford Classification for IgA Nephropathy (VALIGA) update
BACKGROUND: It is unknown whether renal pathology lesions in immunoglobulin A nephropathy (IgAN) correlate with renal outcomes over decades of follow-up. METHODS: In 1130 patients of the original Validation Study of the Oxford Classification for IgA Nephropathy (VALIGA) cohort, we studied the relationship between the MEST score (mesangial hypercellularity, M; endocapillary hypercellularity, E; segmental glomerulosclerosis, S; tubular atrophy/interstitial fibrosis, T), crescents (C) and other histological lesions with both a combined renal endpoint [50% estimated glomerular filtration rate (eGFR) loss or kidney failure] and the rate of eGFR decline over a follow-up period extending to 35 years [median 7 years (interquartile range 4.1-10.8)]. RESULTS: In this extended analysis, M1, S1 and T1-T2 lesions as well as the whole MEST score were independently related with the combined endpoint (P < 0.01), and there was no effect modification by age for these associations, suggesting that they may be valid in children and in adults as well. Only T lesions were associated with the rate of eGFR loss in the whole cohort, whereas C showed this association only in patients not treated with immunosuppression. In separate prognostic analyses, the whole set of pathology lesions provided a gain in discrimination power over the clinical variables alone, which was similar at 5 years (+2.0%) and for the whole follow-up (+1.8%). A similar benefit was observed for risk reclassification analyses (+2.7% and +2.4%). CONCLUSION: Long-term follow-up analyses of the VALIGA cohort showed that the independent relationship between kidney biopsy findings and the risk of progression towards kidney failure in IgAN remains unchanged across all age groups and decades after the renal biopsy
Is there long-term value of pathology scoring in immunoglobulin A nephropathy? A validation study of the Oxford Classification for IgA Nephropathy (VALIGA) update
Background
It is unknown whether renal pathology lesions in immunoglobulin A nephropathy (IgAN) correlate with renal outcomes over decades of follow-up.
Methods
In 1130 patients of the original Validation Study of the Oxford Classification for IgA Nephropathy (VALIGA) cohort, we studied the relationship between the MEST score (mesangial hypercellularity, M; endocapillary hypercellularity, E; segmental glomerulosclerosis, S; tubular atrophy/interstitial fibrosis, T), crescents (C) and other histological lesions with both a combined renal endpoint [50% estimated glomerular filtration rate (eGFR) loss or kidney failure] and the rate of eGFR decline over a follow-up period extending to 35 years [median 7 years (interquartile range 4.1–10.8)].
Results
In this extended analysis, M1, S1 and T1–T2 lesions as well as the whole MEST score were independently related with the combined endpoint (P < 0.01), and there was no effect modification by age for these associations, suggesting that they may be valid in children and in adults as well. Only T lesions were associated with the rate of eGFR loss in the whole cohort, whereas C showed this association only in patients not treated with immunosuppression. In separate prognostic analyses, the whole set of pathology lesions provided a gain in discrimination power over the clinical variables alone, which was similar at 5 years (+2.0%) and for the whole follow-up (+1.8%). A similar benefit was observed for risk reclassification analyses (+2.7% and +2.4%).
Conclusion
Long-term follow-up analyses of the VALIGA cohort showed that the independent relationship between kidney biopsy findings and the risk of progression towards kidney failure in IgAN remains unchanged across all age groups and decades after the renal biopsy
Is there long-term value of pathology scoring in immunoglobulin A nephropathy? A validation study of the Oxford Classification for IgA Nephropathy (VALIGA) update
Background. It is unknown whether renal pathology lesions in immunoglobulin A nephropathy (IgAN) correlate with renal outcomes over decades of follow-up
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
Validation of the Oxford classification of IgA nephropathy in cohorts with different presentations and treatments
Tonsillectomy in a European Cohort of 1,147 Patients with IgA Nephropathy
Background: Tonsillectomy has been considered a treatment for IgA nephropathy (IgAN). It is aimed at removing a source of pathogens, reducing mucosa-associated lymphoid tissue and decreasing polymeric IgA synthesis. However, its beneficial effect is still controversial. In Asia, favorable outcomes have been claimed mostly in association with corticosteroids. In Europe, small, single-center uncontrolled studies have failed to show benefits. Methods: The European validation study of the Oxford classification of IgAN (VALIGA) collected data from 1,147 patients with IgAN over a follow-up of 4.7 years. We investigated the outcome of progression to end-stage renal disease (ESRD) and/or 50% loss of estimated glomerular filtration rate (eGFR) and the annual loss of eGFR in 61 patients who had had tonsillectomy. Results: Using the propensity score, which is a logistic regression model, we paired 41 patients with tonsillectomy and 41 without tonsillectomy with similar risk of progression (gender, age, race, mean blood pressure, proteinuria, eGFR at renal biopsy, previous treatments and Oxford MEST scores). No significant difference was found in the outcome. Moreover, we performed an additional propensity score pairing 17 patients who underwent tonsillectomy after the diagnosis of IgAN and 51 without tonsillectomy with similar risk of progression at renal biopsy and subsequent treatments. No significant difference was found in changes in proteinuria, or in the renal end point of 50% reduction in GFR and/or ESRD, or in the annual loss of eGFR. Conclusion: In the large VALIGA cohort of European subjects with IgAN, no significant correlation was found between tonsillectomy and renal function decline