ABSTRACT
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Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Inappropriate Prescribing/statistics & numerical data , Potentially Inappropriate Medication List/statistics & numerical data , Dialysis , Renal Insufficiency/therapyABSTRACT
Background: Association between poor control of glycemia and the onset of microvascular complications in type 2 diabetes mellitus (T2DM) patients is a hard issue. However, it seems that the impact of pharmacological treatment is important only in early stages of diabetic nephropathy. We sought to examine whether intensive glycemic control is associated with improvement of clinical Chronic Kidney Disease (CKD) outcomes compared to standard glycemic control. Methods: Meta-analysis of published and unpublished randomized controlled trials (RCT) and post-hoc analysis of RCTs comparing anti-diabetic drugs and/or insulin (intensive control) vs. dietary measures (standard control) for relevant outcomes related to progression of CKD clinically manifest was undertaken. Summary estimates obtained by random effects model and funnel plots for assessing reporting bias are presented. Results: Our analysis was based on four RCTs representing 27,391 adult T2DM patients with CKD from around the world. The pooled OR for the outcomes of doubling of serum creatinine and need of dialysis were, respectively, of 0.98 with 95% confidence interval (95% CI) 0.81-1.19, and 0.84 with 95% CI 0.69-1.02. The pooled OR for the outcome of death from kidney failure was 0.62 with 95% CI 0.39-0.98. Clinical differences between studies were not translated in statistical heterogeneity. Reporting bias may be present. Conclusions: Intensive glycemic control has an effect on death from kidney failure compared to standard glycemic control. Better comprehension of glycemic control effects on both T2DM patients with and without CKD is important for individualization of these two treatment modalities.
ABSTRACT
Fundamento y objetivo: Las células T reguladoras circulantes podrían convertirse en un adecuado biomarcador para los trasplantados renales. El objetivo de este estudio es evaluar el efecto de los inhibidores de la mammalian target of rapamycin (I-mTOR, «diana de rapamicina en células de mamífero») en las células reguladoras, y el interés clínico de este efecto. Material y métodos: Revisión sistemática de trabajos publicados y no publicados. Bases de datos y repositorios del mundo entero. Se buscaron ensayos controlados aleatorizados y estudios de cohortes que compararon recuentos de células reguladoras y episodios de rechazo entre trasplantados tratados con y sin I-mTOR. Los trabajos podían medir la correlación células reguladoras-filtrado glomerular. Se evaluó la codependencia células reguladoras-eficacia de los I-mTOR. Resultados: Se incluyeron 5 ensayos y 9 estudios. Las diferencias clínicas no permitieron una estimación cuantitativa del efecto de la inmunosupresión en el número de células reguladoras. Sin embargo, observamos que hay más células reguladoras con sirolimus o everolimus. El número de episodios de rechazo fue similar con anticalcineurínicos que con I-mTOR, a pesar de las diferencias en el número de células reguladoras. La correlación combinada células reguladoras-filtrado glomerular fue prospectivamente de 0,114, con un intervalo de confianza al 95% (IC 95%) de 0,062-0,406, y retrospectivamente, de 0,13 (IC 95% 0,0-0,361). Existen pruebas directas, aunque de bajo nivel (aleatorización estratificada por el biomarcador), respecto a la codependencia células reguladoras-eficacia de los I-mTOR. Conclusión: El número de células reguladoras puede asociarse a buenos resultados o desenlaces en los tratados con I-mTOR (eficacia antirrechazo), considerando la relación entre estas células y la función del injerto. Registro: PROSPERO (CRD42016046285) (AU)
Background and objective: Circulating regulatory T cells could become a suitable biomarker for kidney recipients. The objective of this study was to evaluate the effect of mammalian target of rapamycin (mTOR) inhibitors on regulatory T cell numbers, and the clinical interest of this effect. Material and methods: Systematic review of published and unpublished studies. Worldwide databases or repositories. Randomised controlled trials and cohort studies comparing regulatory T cell counts and rejection episodes between patients with and without mTOR inhibitors were searched. Correlation of regulatory T cells-glomerular filtration rate might be supplied. Co-dependency regulatory T cells-mTOR inhibitors efficacy was evaluated. Results: Five trials and 9 studies were included. Clinical differences made it difficult to obtain quantitative estimates of the effect of immunosuppression on regulatory T cell numbers. Nevertheless, we found that there are higher regulatory T cell numbers under treatment with sirolimus or everolimus. Rejection episodes were similar under calcineurin inhibitors and mTOR inhibitors despite different regulatory T cell numbers. Pooled correlation regulatory T cells-glomerular filtration rate was, prospectively 0.114 (95% confidence interval [95% CI] 0.062-0.406), and retrospectively 0.13 (95% CI 0.0-0.361). There is direct evidence although of low level (biomarker-stratified randomisation) on the co-dependency regulatory T cells-mTOR inhibitors efficacy. Conclusions: Regulatory T cells counts may be associated with better outcomes under treatment with mTOR inhibitors (anti-rejection efficacy), considering that there is a relationship between these cells and kidney graft function Registration: PROSPERO (CRD42016046285) (AU)
Subject(s)
Humans , Cell Count , Biomarkers/analysis , Kidney Transplantation/methods , Graft Rejection/diagnosis , Cohort Studies , Glomerular Filtration Rate/physiology , BiasABSTRACT
BACKGROUND AND OBJECTIVE: Circulating regulatory T cells could become a suitable biomarker for kidney recipients. The objective of this study was to evaluate the effect of mammalian target of rapamycin (mTOR) inhibitors on regulatory T cell numbers, and the clinical interest of this effect. MATERIAL AND METHODS: Systematic review of published and unpublished studies. Worldwide databases or repositories. Randomised controlled trials and cohort studies comparing regulatory T cell counts and rejection episodes between patients with and without mTOR inhibitors were searched. Correlation of regulatory T cells-glomerular filtration rate might be supplied. Co-dependency regulatory T cells-mTOR inhibitors efficacy was evaluated. RESULTS: Five trials and 9 studies were included. Clinical differences made it difficult to obtain quantitative estimates of the effect of immunosuppression on regulatory T cell numbers. Nevertheless, we found that there are higher regulatory T cell numbers under treatment with sirolimus or everolimus. Rejection episodes were similar under calcineurin inhibitors and mTOR inhibitors despite different regulatory T cell numbers. Pooled correlation regulatory T cells-glomerular filtration rate was, prospectively 0.114 (95% confidence interval [95% CI] 0.062-0.406), and retrospectively 0.13 (95% CI 0.0-0.361). There is direct evidence although of low level (biomarker-stratified randomisation) on the co-dependency regulatory T cells-mTOR inhibitors efficacy. CONCLUSIONS: Regulatory T cells counts may be associated with better outcomes under treatment with mTOR inhibitors (anti-rejection efficacy), considering that there is a relationship between these cells and kidney graft function. REGISTRATION: PROSPERO (CRD42016046285).
Subject(s)
Graft Rejection/prevention & control , Immunosuppressive Agents/therapeutic use , Kidney Transplantation , T-Lymphocytes, Regulatory/metabolism , TOR Serine-Threonine Kinases/antagonists & inhibitors , Biomarkers/blood , Graft Rejection/blood , Graft Rejection/diagnosis , Graft Rejection/immunology , Humans , Lymphocyte Count , Treatment OutcomeABSTRACT
No disponible
Subject(s)
Humans , Medication Reconciliation , Medication Errors/prevention & control , Drug Prescriptions/standards , Patient Discharge/standardsABSTRACT
No disponible
Subject(s)
Humans , Male , Aged , Acute Kidney Injury/etiology , Complement System Proteins/deficiency , Nephritis, Interstitial/chemically induced , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Diagnosis, Differential , BiopsySubject(s)
Acute Kidney Injury/etiology , Glomerulonephritis, Membranoproliferative/complications , Nephritis, Interstitial/diagnosis , Aged , Diagnosis, Differential , Emergencies , Fluorescent Antibody Technique, Direct , Glomerulonephritis, Membranoproliferative/diagnosis , Humans , Lupus Nephritis/diagnosis , Male , Nephritis, Interstitial/blood , Nephritis, Interstitial/complications , Sjogren's Syndrome/diagnosisABSTRACT
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