Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 17 de 17
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
País de afiliación
Intervalo de año de publicación
1.
Kidney Int ; 100(6): 1316-1324, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34560140

RESUMEN

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis can present with life-threatening lung-kidney syndromes. However, many controlled treatment trials excluded patients with diffuse alveolar hemorrhage or severely impaired glomerular filtration rates, and so the optimum treatment in these cases is unclear. In this retrospective cohort study, we report the outcomes of 64 patients with life-threatening disease treated with a combination regimen of rituximab, low-dose intravenous cyclophosphamide, oral glucocorticoids, and plasma exchange. At entry, the median estimated glomerular filtration rate was 9 mL/min, 47% of patients required dialysis, and 52% had diffuse alveolar hemorrhage. All patients received a minimum of seven plasma exchanges, and the median cumulative doses of rituximab, cyclophosphamide, and glucocorticoid were 2, 3, and 2.6 g, respectively, at six months. A total of 94% of patients had achieved disease remission (version 3 Birmingham Vasculitis Activity Score of 0) at this time point, and 67% of patients who required dialysis recovered independent kidney function. During long-term follow-up (median duration 46 months), overall patient survival was 85%, and 69% of patients remained free from end-stage kidney disease, which compares favorably to a historic cohort with severe disease treated with a conventional induction regimen. Combination treatment was associated with prolonged B cell depletion and low rates of relapse; 87% of patients were in continuous remission at month 36. The serious infection rate during total follow-up was 0.28 infections/patient/year, suggesting that combination treatment is not associated with an enduring risk of infection. Thus, we suggest that combination immunosuppressive therapy may permit glucocorticoid avoidance and provide rapid and prolonged disease control in patients with severe ANCA-associated vasculitis.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Anticuerpos Anticitoplasma de Neutrófilos , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/tratamiento farmacológico , Ciclofosfamida/efectos adversos , Quimioterapia Combinada , Humanos , Inmunosupresores/efectos adversos , Intercambio Plasmático , Inducción de Remisión , Estudios Retrospectivos , Rituximab/efectos adversos
2.
Kidney Int ; 95(3): 655-665, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30655025

RESUMEN

Complement plays an important role in the pathogenesis of lupus nephritis (LN). With the emergence of therapeutic complement inhibition, there is a need to identify patients in whom complement-driven inflammation is a major cause of kidney injury in LN. Clinical and histopathological data were obtained retrospectively from 57 biopsies with class III, IV, and V LN. Biopsies were stained for complement components C9, C5b-9, C3c, and C3d and for the macrophage marker CD68. C9 and C5b-9 staining were highly correlated (r = 0.92 in the capillary wall). C5b-9 staining was detected in the mesangium and/or capillary wall of both active and chronic proliferative LN in all but one biopsy and in the capillary wall of class V LN in all biopsies. C5b-9 staining intensity in the tubular basement membrane correlated with markers of tubulointerstitial damage, and more intense capillary wall C5b-9 staining was significantly associated with nonresponse to conventional treatment. Glomerular C5b-9 staining intensity did not differ between active and chronic disease; in contrast, C3c and CD68 staining were associated with active disease. Evaluation of serial biopsies and comparison of staining in active and chronic LN demonstrated that C5b-9 staining persisted for months to years. These results suggest that C5b-9 staining is almost always present in LN, resolves slowly, and is not a reliable marker of ongoing glomerular C5 activation. This limits the utility of C5b-9 staining to identify patients who are most likely to benefit from C5 inhibition.


Asunto(s)
Activación de Complemento , Complemento C5/inmunología , Complejo de Ataque a Membrana del Sistema Complemento/análisis , Glomérulos Renales/patología , Nefritis Lúpica/inmunología , Adolescente , Adulto , Anciano , Biomarcadores/análisis , Biopsia , Complemento C5/antagonistas & inhibidores , Complejo de Ataque a Membrana del Sistema Complemento/inmunología , Femenino , Humanos , Inmunosupresores/farmacología , Inmunosupresores/uso terapéutico , Glomérulos Renales/inmunología , Nefritis Lúpica/tratamiento farmacológico , Nefritis Lúpica/patología , Masculino , Persona de Mediana Edad , Selección de Paciente , Reproducibilidad de los Resultados , Estudios Retrospectivos , Adulto Joven
3.
Rheumatology (Oxford) ; 58(2): 260-268, 2019 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-30239910

RESUMEN

Objectives: Glucocorticoids (GCs) are a mainstay of treatment for patients with ANCA-associated vasculitis (AAV) but are associated with significant adverse effects. Effective remission induction in severe AAV using extremely limited GC exposure has not been attempted. We tested an early rapid GC withdrawal induction regimen for patients with severe AAV. Methods: Patients with active MPO- or PR3-ANCA vasculitis or ANCA-negative pauci-immune glomerulonephritis were included. Induction treatment consisted of two doses of rituximab, 3 months of low-dose CYC and a short course of oral GC (for between 1 and 2 weeks). Clinical, biochemical and immunological outcomes as well as adverse events were recorded. Results: A total of 49 patients were included, with at least 12 months of follow-up in 46. All patients achieved remission, with decreases observed in creatinine, proteinuria, CRP, ANCA level and BVAS. Three patients requiring dialysis at presentation became dialysis independent. Two patients required the introduction of maintenance GC for treatment of vasculitis. Overall outcomes were comparable to those of two matched cohorts (n = 172) from previous European Vasculitis Society (EUVAS) trials, but with lower total exposure to CYC and GCs (P < 0.001) and reduced rates of severe infections (P = 0.02) compared with the RITUXVAS (rituximab versus cyclophosphamide in AAV) trial. We found no new cases of diabetes in the first year compared with historic rates of 8.2% from the EUVAS trials (P = 0.04). Conclusion: Early GC withdrawal in severe AAV is as effective for remission induction as the standard of care and is associated with reduced GC-related adverse events.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/tratamiento farmacológico , Glucocorticoides/administración & dosificación , Enfermedad Aguda , Administración Oral , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Ciclofosfamida/uso terapéutico , Esquema de Medicación , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Glucocorticoides/efectos adversos , Glucocorticoides/uso terapéutico , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Recurrencia , Inducción de Remisión , Rituximab/administración & dosificación , Rituximab/efectos adversos , Rituximab/uso terapéutico , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto Joven
4.
Nephrol Dial Transplant ; 34(1): 63-73, 2019 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-29462348

RESUMEN

Background: Current guidelines advise that rituximab or cyclophosphamide should be used for the treatment of organ-threatening disease in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV), although few studies have examined the efficacy and safety of these agents in combination. Methods: We conducted a single-centre cohort study of 66 patients treated with a combination of oral corticosteroids, rituximab and low-dose pulsed intravenous cyclophosphamide followed by a maintenance regimen of azathioprine and tapered steroid for the treatment of biopsy-proven renal involvement in AAV. Patients were followed for a median of 56 months. Case-control analysis with 198 propensity-matched cases from European Vasculitis Study Group (EUVAS) trials compared long-term differences in relapse-free, renal and patient survival. Results: At entry, the median Birmingham Vasculitis Activity Score (BVAS) was 19 and estimated glomerular filtration rate was 25 mL/min. Cumulative doses of rituximab, cyclophosphamide and corticosteroids were 2, 3 and 4.2 g, respectively, at 6 months. A total of 94% of patients achieved disease remission by 6 months (BVAS < 0) and patient and renal survival were 84 and 95%, respectively, at 5 years. A total of 84% achieved ANCA-negative status and 57% remained B cell deplete at 2 years, which was associated with low rates of major relapse (15% at 5 years). The serious infection rate during long-term follow-up was 1.24 per 10 patient-years. Treatment with this regimen was associated with a reduced risk of death {hazard ratio [HR] 0.29 [95% confidence interval (CI) 0.125-0.675], P = 0.004}, progression to end-stage renal disease (ESRD) [HR 0.20 (95% CI 0.06-0.65), P = 0.007] and relapse [HR 0.49 (95% CI 0.25-0.97), P = 0.04] compared with propensity-matched patients enrolled in EUVAS trials. Conclusions: This regimen is potentially superior to current standards of care, and controlled studies are warranted to establish the utility of combination drug approaches in the treatment of AAV.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedades Renales/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Azatioprina/administración & dosificación , Estudios de Casos y Controles , Estudios de Cohortes , Ciclofosfamida/administración & dosificación , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Humanos , Fallo Renal Crónico/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Pronóstico , Inducción de Remisión , Rituximab/administración & dosificación , Tasa de Supervivencia , Adulto Joven
5.
BMC Nephrol ; 20(1): 352, 2019 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-31492152

RESUMEN

BACKGROUND: Tacrolimus (TAC) is effective in treating membranous nephropathy (MN); however relapses are frequent after treatment cessation. We conducted a randomised controlled trial to examine whether the addition of mycophenolate mofetil (MMF) to TAC would reduce relapse rate. METHODS: Forty patients with biopsy proven idiopathic MN and nephrotic syndrome were randomly assigned to receive either TAC monotherapy (n = 20) or TAC combined with MMF (n = 20) for 12 months. When patients had been in remission for 1 year on treatment the MMF was stopped and the TAC gradually withdrawn in both groups over 6 months. Patients also received supportive treatment with angiotensin blockade, statins, diuretics and anticoagulation as needed. Primary endpoint was relapse rate following treatment withdrawal. Secondary outcomes were remission rate, time to remission and change in renal function. RESULTS: 16/20 (80%) of patients in the TAC group achieved remission compared to 19/20 (95%) in the TAC/MMF group (p = 0.34). The median time to remission in the TAC group was 54 weeks compared to 40 weeks in the TAC/MMF group (p = 0.46). There was no difference in the relapse rate between the groups: 8/16 (50%) patients in the TAC group relapsed compared to 8/19 (42%) in the TAC/MMF group (p = 0.7). The addition of MMF to TAC did not adversely affect the safety of the treatment. CONCLUSIONS: Addition of MMF to TAC does not alter the relapse rate of nephrotic syndrome in patients with MN. TRIAL REGISTRATION: This trial is registered with EudraCTN2008-001009-41 . Trial registration date 2008-10-08.


Asunto(s)
Glomerulonefritis Membranosa/diagnóstico , Glomerulonefritis Membranosa/tratamiento farmacológico , Inmunosupresores/administración & dosificación , Ácido Micofenólico/administración & dosificación , Tacrolimus/administración & dosificación , Adulto , Anciano , Quimioterapia Combinada , Femenino , Glomerulonefritis Membranosa/sangre , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Inducción de Remisión/métodos , Adulto Joven
6.
Rheumatology (Oxford) ; 57(7): 1156-1161, 2018 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-29562252

RESUMEN

OBJECTIVE: B cell depletion, most commonly with rituximab, is an evolving therapeutic approach in SLE. Infusion reactions after rituximab are common, and may prevent re-treatment in patients who previously demonstrated beneficial response. We have used ofatumumab, a fully humanized anti-CD20 mAb, as an alternative B cell-depleting agent in patients with SLE who are rituximab-intolerant due to severe infusion reactions. METHODS: A single-centre retrospective case series of 16 patients were treated with ofatumumab for SLE between 2012 and 2015. RESULTS: Ofatumumab infusion was well tolerated in 14/16 patients, in whom the median age was 34 (range 19-55) and the median duration of SLE 9.2 years (0.6-28.5). The cohort was heavily pre-treated, with 50% having prior CYC exposure, and a median cumulative dose of prior rituximab 4 g (1-6). Twelve patients were treated for LN, one for extra-renal flare and one for remission maintenance. B cell-depletion was achieved in 12/14 patients, with comparable reconstitution kinetics to a previous cohort treated with rituximab at our centre, and was associated with improvements in serological markers of disease activity, including ANA, anti-dsDNA antibody and complement levels. Half of the patients with LN achieved renal remission by 6 months. Progressive disease that was unresponsive to augmented immunosuppression with CYC was seen in five patients. During long-term follow-up (median 28 months), five grade III infections were reported, and there were no malignancies or deaths. CONCLUSION: In this pre-treated cohort with long-standing SLE, ofatumumab was a well-tolerated, safe and effective alternative to rituximab for B cell-depletion therapy.

7.
Rheumatology (Oxford) ; 56(7): 1206-1216, 2017 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-28387859

RESUMEN

Objectives: The aim was to investigate whether the signalling lymphocyte activation molecule (SLAM) signalling pathways contribute to LN and whether SLAM receptors could be valuable biomarkers of disease activity. Methods: Peripheral blood mononuclear cells from 30National Research Ethics Service SLE patients with biopsy-proven LN were analysed by flow cytometry. Clinical measures of disease activity were assessed. The expression of the SLAM family receptors on T-cell subpopulations [CD4, CD8 and double negative (DN) T cells] was measured and compared between lupus patients with active renal disease and those in remission. Results: The frequency of CD8 T cells expressing SLAMF3, SLAMF5 and SLAMF7 was significantly lower in LN patients who were in remission. In contrast, these subsets were similar in patients with active renal disease and in healthy individuals. Patients with active nephritis had an increased percentage of circulating monocytes, consistent with a potential role played by these cells in glomerular inflammation. Changes in the frequency of DN T cells positive for SLAMF2, SLAMF4 and SLAMF7 were observed in lupus patients irrespective of the disease activity. We detected alterations in the cellular expression of the SLAM family receptors, but these changes were less obvious and did not reveal any specific pattern. The percentage of DN T cells expressing SLAMF6 could predict the clinical response to B-cell depletion in patients with LN. Conclusion: Our study demonstrates altered expression of the SLAM family receptors in SLE T lymphocytes. This is consistent with the importance of the SLAM-associated pathways in lupus pathogenesis.


Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Nefritis Lúpica/tratamiento farmacológico , Nefritis Lúpica/inmunología , Rituximab/uso terapéutico , Proteína Asociada a la Molécula de Señalización de la Activación Linfocitaria/metabolismo , Adulto , Antígenos CD/metabolismo , Linfocitos B/efectos de los fármacos , Linfocitos B/inmunología , Biomarcadores/metabolismo , Biopsia con Aguja , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/metabolismo , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Humanos , Inmunohistoquímica , Infusiones Intravenosas , Leucocitos Mononucleares/metabolismo , Nefritis Lúpica/patología , Activación de Linfocitos/inmunología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Medición de Riesgo , Índice de Severidad de la Enfermedad , Proteína Asociada a la Molécula de Señalización de la Activación Linfocitaria/inmunología , Estadísticas no Paramétricas , Resultado del Tratamiento
8.
Rheumatology (Oxford) ; 55(8): 1437-42, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27094598

RESUMEN

OBJECTIVES: B cell depletion is an effective treatment strategy in ANCA-associated vasculitis (AAV). Ofatumumab is a fully humanized anti-CD20 mAb that has shown efficacy in the treatment of haematological malignancy and RA. The use of ofatumumab in the treatment of AAV has not previously been reported. METHODS: This study was based on a case series of eight patients who received ofatumumab, in conjunction with low-dose CYC and oral steroids, in the treatment of AAV. RESULTS: Eight patients received ofatumumab: seven for remission induction in active disease (three relapsing; four with new disease) and one for remission maintenance. B cell depletion was achieved in all patients by 1 month, and was sustained for at least 6 months. All patients with active disease achieved clinical remission (BVAS of zero, or BVAS ⩽5 if all scores due to persistent urinary abnormalities in the presence of stable or improving renal function) by 3 months. This was associated with a rapid fall in ANCA titres, reduced inflammatory responses and improvements in renal function. At 12 months, three patients had repopulated B cells associated with the recurrence of circulating ANCAs, although no patients experienced major clinical relapse in the first 24 months. No unexpected side effects were observed. CONCLUSION: Treatment with ofatumumab resulted in similar serological and clinical responses to those seen in previous cohorts treated at our centre with a comparable CS, CYC and rituximab-based regimen. Ofatumumab should be considered an alternative B cell depleting agent in patients who are intolerant of, or unresponsive to, rituximab.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/terapia , Anticuerpos Monoclonales/uso terapéutico , Factores Inmunológicos/uso terapéutico , Depleción Linfocítica/métodos , Adulto , Anciano , Anticuerpos Monoclonales Humanizados , Linfocitos B , Femenino , Humanos , Masculino , Persona de Mediana Edad , Inducción de Remisión/métodos , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/terapia , Adulto Joven
12.
Lupus Sci Med ; 9(1)2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-35074933

RESUMEN

OBJECTIVE: To explore the utility of the NanoString platform in elucidating kidney immune transcripts for class III, IV and V lupus nephritis (LN) using a retrospective cohort of formalin-fixed paraffin-embedded (FFPE) kidney biopsy tissue. METHODS: Immune gene transcript analysis was performed using the NanoString nCounter platform on RNA from LN (n=55), thin basement membrane (TBM) disease (n=14) and membranous nephropathy (MN) (n=9) FFPE kidney biopsy tissue. LN samples consisted of single class III (n=11), IV (n=23) and V (n=21) biopsies with no mixed lesions. Differential gene expression was performed with NanoString nSolver, with visualisations of volcano plots and heatmaps generated in R. Significant transcripts were interrogated to identify functional networks using STRING and Gene ontogeny terms. RESULTS: In comparison to TBM, we identified 52 significantly differentially expressed genes common to all three LN classes. Pathway analysis showed enrichment for type I interferon (IFN) signalling, complement and MHC II pathways, with most showing the highest expression in class IV LN. Our class IV LN biopsies also showed significant upregulation of NF-κB signalling and immunological enrichment in comparison to class V LN biopsies. Transcripts from the type I IFN pathway distinguished class V LN from MN. CONCLUSION: Our whole kidney section transcriptomic analysis provided insights into the molecular profile of class III, IV and V LN. The data highlighted important pathways common to all three classes and pathways enriched in our class IV LN biopsies. The ability to reveal molecular pathways in LN using FFPE whole biopsy sections could have clinical utility in treatment selection for LN.


Asunto(s)
Lupus Eritematoso Sistémico , Nefritis Lúpica , Expresión Génica , Humanos , Riñón , Lupus Eritematoso Sistémico/patología , Estudios Retrospectivos
13.
Nat Commun ; 12(1): 1980, 2021 03 31.
Artículo en Inglés | MEDLINE | ID: mdl-33790300

RESUMEN

The majority of patients with systemic lupus erythematosus (SLE) have high expression of type I IFN-stimulated genes. Mitochondrial abnormalities have also been reported, but the contribution of type I IFN exposure to these changes is unknown. Here, we show downregulation of mitochondria-derived genes and mitochondria-associated metabolic pathways in IFN-High patients from transcriptomic analysis of CD4+ and CD8+ T cells. CD8+ T cells from these patients have enlarged mitochondria and lower spare respiratory capacity associated with increased cell death upon rechallenge with TCR stimulation. These mitochondrial abnormalities can be phenocopied by exposing CD8+ T cells from healthy volunteers to type I IFN and TCR stimulation. Mechanistically these 'SLE-like' conditions increase CD8+ T cell NAD+ consumption resulting in impaired mitochondrial respiration and reduced cell viability, both of which can be rectified by NAD+ supplementation. Our data suggest that type I IFN exposure contributes to SLE pathogenesis by promoting CD8+ T cell death via metabolic rewiring.


Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Perfilación de la Expresión Génica/métodos , Interferón Tipo I/inmunología , Lupus Eritematoso Sistémico/inmunología , Adulto , Anciano , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/metabolismo , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Femenino , Humanos , Interferón Tipo I/metabolismo , Interferón Tipo I/farmacología , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/metabolismo , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/genética , Activación de Linfocitos/inmunología , Redes y Vías Metabólicas/genética , Persona de Mediana Edad , Mitocondrias/efectos de los fármacos , Mitocondrias/genética , Mitocondrias/metabolismo , Adulto Joven
15.
Clin J Am Soc Nephrol ; 15(2): 209-218, 2020 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-31953303

RESUMEN

BACKGROUND AND OBJECTIVES: Minimal change disease is an important cause of nephrotic syndrome in adults. Corticosteroids are first-line therapy for minimal change disease, but a prolonged course of treatment is often required and relapse rates are high. Patients with minimal change disease are therefore often exposed to high cumulative corticosteroid doses and are at risk of associated adverse effects. This study investigated whether tacrolimus monotherapy without corticosteroids would be effective for the treatment of de novo minimal change disease. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a multicenter, prospective, open-label, randomized, controlled trial involving six nephrology units across the United Kingdom. Adult patients with first presentation of minimal change disease and nephrotic syndrome were randomized to treatment with either oral tacrolimus at 0.05 mg/kg twice daily, or prednisolone at 1 mg/kg daily up to 60 mg daily. The primary outcome was complete remission of nephrotic syndrome after 8 weeks of therapy. Secondary outcomes included remission of nephrotic syndrome at 16 and 26 weeks, rates of relapse of nephrotic syndrome, and changes from baseline kidney function. RESULTS: There were no significant differences between the tacrolimus and prednisolone treatment cohorts in the proportion of patients in complete remission at 8 weeks (21 out of 25 [84%] for prednisolone and 17 out of 25 [68%] for tacrolimus cohorts; P=0.32; difference in remission rates was 16%; 95% confidence interval [95% CI], -11% to 40%), 16 weeks (23 out of 25 [92%] for prednisolone and 19 out of 25 [76%] for tacrolimus cohorts; P=0.25; difference in remission rates was 16%; 95% CI, -8% to 38%), or 26 weeks (23 out of 25 [92%] for prednisolone and 22 out of 25 [88%] for tacrolimus cohorts; P=0.99; difference in remission rates was 4%; 95% CI, -17% to 25%). There was no significant difference in relapse rates (17 out of 23 [74%] for prednisolone and 16 out of 22 [73%] for tacrolimus cohorts) for patients in each group who achieved complete remission (P=0.99) or in the time from complete remission to relapse. CONCLUSIONS: Tacrolimus monotherapy can be effective alternative treatment for patients wishing to avoid steroid therapy for minimal change disease. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_01_16_CJN06180519.mp3.


Asunto(s)
Corticoesteroides/uso terapéutico , Inhibidores de la Calcineurina/uso terapéutico , Inmunosupresores/uso terapéutico , Nefrosis Lipoidea/tratamiento farmacológico , Prednisolona/uso terapéutico , Tacrolimus/uso terapéutico , Adolescente , Corticoesteroides/efectos adversos , Adulto , Anciano , Inhibidores de la Calcineurina/efectos adversos , Femenino , Humanos , Inmunosupresores/efectos adversos , Masculino , Persona de Mediana Edad , Nefrosis Lipoidea/diagnóstico , Prednisolona/efectos adversos , Estudios Prospectivos , Recurrencia , Inducción de Remisión , Tacrolimus/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Reino Unido , Adulto Joven
16.
Nephrol Dial Transplant ; 19(12): 3062-7, 2004 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-15507477

RESUMEN

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) commonly presents with nephrotic syndrome (NS), and spontaneous remission is rare. NS is a poor prognostic marker for renal survival, and has serious extra-renal complications. Rapid remission using drugs with minimal side effects is desirable. Tacrolimus (Tac) has a more potent immunosuppressive effect and may be less toxic at therapeutic doses than ciclosporin (CsA). Although CsA has a role in the treatment of FSGS, there are limited data regarding the use of Tac monotherapy in this setting, and this is limited to experience in children. METHODS: We prospectively report the outcome for six adult patients with FSGS treated with Tac from first presentation with NS, and for a further five adult patients in remission on CsA converted to Tac in an attempt to arrest a progressive decline in renal function on CsA. RESULTS: All six patients treated with Tac from presentation with NS achieved remission after 6.5 +/- 5.9 months. The serum albumin for the group increased from 26.8 +/- 4.6 to 37.7 +/- 1.9 g/l (P = 0.003), and there was a significant reduction in the mean 24 h urinary protein excretion from 11.0 +/- 4.5 to 2.8 +/- 2.5 g (P = 0.003). All remissions were partial with a mean reduction in 24 h urinary protein of 75.2 +/- 16.8%. There was a non-significant reduction in MDRD GFR from 71.7 +/- 22.4 to 55.9 +/- 9.7 ml/min/1.73 m(2) (P = 0.07), which manifest within the first 3 months of Tac treatment but renal function was subsequently stable. The mean follow-up for the group was 12.8+/-5.5 months. Two of the five patients converted from CsA to Tac maintained complete remission, and the remaining three patients in partial remission had further reductions in proteinuria. There was an improvement in renal function concomitant with conversion to Tac in each case, with an overall improvement in MDRD GFR for the group of +1.9+/-1.1 ml/min/1.73 m(2)/month. CONCLUSIONS: Tac rapidly and effectively induced remission of NS in FSGS. Conversion from CsA to Tac indicates that Tac might be a more potent agent with less nephrotoxicity in this setting.


Asunto(s)
Nefropatías Diabéticas/tratamiento farmacológico , Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Tacrolimus/uso terapéutico , Adulto , Albuminuria , Ciclosporina/uso terapéutico , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Humanos , Inmunosupresores/uso terapéutico , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Proteinuria , Factores de Tiempo , Resultado del Tratamiento
17.
Nephrol Dial Transplant ; 19(11): 2816-22, 2004 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-15340094

RESUMEN

BACKGROUND: Vascular access is judged on its ability to provide good dialysis adequacy, its durability and complication rates. Formation of a functional arteriovenous fistula is desirable but difficult to achieve in a significant proportion of patients. We report the large-scale use of Tesio-Caths, a twin-line single-lumen central venous catheter, to maximize dialysis adequacy where formation of an arteriovenous fistula was not possible. METHODS: All patients who had Tesio-Caths inserted between 1 January 1999 and 1 October 2002 were studied. RESULTS: Six hundred and twenty-three Tesio-Caths were inserted from 1 January 1999 to 1 October 2002 in 435 patients, generating 7464 patient months of follow-up. Five hundred and ninety-four out of 623 (95.3%) Tesio-Caths were immediately functional. Mean dialysis adequacy measured by single-pool Kt/V was 1.5+/-0.3 for all Tesio-Caths for the entire period of study, with 68% of Tesio-Caths delivering a Kt/V >1.4. Cumulative functional Tesio-Cath survival to final failure was 77.8 and 44% at 1 and 3 years, respectively. Cumulative patient survival was 84.7, 71.4 and 63% at 1, 2 and 3 years, respectively. Access-related infection accounted for 0.28 admissions/1000 catheter days, and the death rate from access-related sepsis was 9.6 deaths/1000 patient years at risk. The admission rate for access dysfunction was 0.33/1000 patient years at risk. CONCLUSION: Tesio-Caths provide good dialysis adequacy for patients in whom an arteriovenous fistula cannot be formed. Patient and functional access survival for this group was comparable with current European data irrespective of vascular access type. Complication rates were acceptably low.


Asunto(s)
Cateterismo Venoso Central , Catéteres de Permanencia , Diálisis Renal , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Cateterismo Venoso Central/efectos adversos , Diseño de Equipo , Femenino , Humanos , Fallo Renal Crónico , Masculino , Persona de Mediana Edad , Diálisis Renal/efectos adversos , Sepsis/etiología , Sepsis/microbiología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA