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1.
Ann Rheum Dis ; 83(1): 15-29, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-37827694

RESUMO

OBJECTIVES: To update the EULAR recommendations for the management of systemic lupus erythematosus (SLE) based on emerging new evidence. METHODS: An international Task Force formed the questions for the systematic literature reviews (January 2018-December 2022), followed by formulation and finalisation of the statements after a series of meetings. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned, and participants finally provided their level of agreement with each item. RESULTS: The Task Force agreed on 5 overarching principles and 13 recommendations, concerning the use of hydroxychloroquine (HCQ), glucocorticoids (GC), immunosuppressive drugs (ISDs) (including methotrexate, mycophenolate, azathioprine, cyclophosphamide (CYC)), calcineurin inhibitors (CNIs, cyclosporine, tacrolimus, voclosporin) and biologics (belimumab, anifrolumab, rituximab). Advice is also provided on treatment strategies and targets of therapy, assessment of response, combination and sequential therapies, and tapering of therapy. HCQ is recommended for all patients with lupus at a target dose 5 mg/kg real body weight/day, considering the individual's risk for flares and retinal toxicity. GC are used as 'bridging therapy' during periods of disease activity; for maintenance treatment, they should be minimised to equal or less than 5 mg/day (prednisone equivalent) and, when possible, withdrawn. Prompt initiation of ISDs (methotrexate, azathioprine, mycophenolate) and/or biological agents (anifrolumab, belimumab) should be considered to control the disease and facilitate GC tapering/discontinuation. CYC and rituximab should be considered in organ-threatening and refractory disease, respectively. For active lupus nephritis, GC, mycophenolate or low-dose intravenous CYC are recommended as anchor drugs, and add-on therapy with belimumab or CNIs (voclosporin or tacrolimus) should be considered. Updated specific recommendations are also provided for cutaneous, neuropsychiatric and haematological disease, SLE-associated antiphospholipid syndrome, kidney protection, as well as preventative measures for infections, osteoporosis, cardiovascular disease. CONCLUSION: The updated recommendations provide consensus guidance on the management of SLE, combining evidence and expert opinion.


Assuntos
Azatioprina , Lúpus Eritematoso Sistêmico , Humanos , Azatioprina/uso terapêutico , Tacrolimo/uso terapêutico , Rituximab/uso terapêutico , Metotrexato/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Imunossupressores/uso terapêutico , Ciclofosfamida/uso terapêutico , Hidroxicloroquina/uso terapêutico , Glucocorticoides/uso terapêutico , Inibidores Enzimáticos/uso terapêutico
2.
Artigo em Inglês | MEDLINE | ID: mdl-39037915

RESUMO

OBJECTIVES: The optimal duration of immunosuppressive (IS) treatment for lupus nephritis (LN) remains uncertain. We assessed the prevalence and predictors of IS tapering and discontinuation (D/C) in LN patients. METHODS: Data from 137 inception cohort LN patients were analyzed. We examined determinants of flares during tapering and after IS D/C, D/C achievement and time to D/C, and adverse long-term outcomes applying logistic and linear regression models. RESULTS: IS tapering was attempted in 111 (81%) patients, and D/C was achieved in 67.5%. Longer time to achieve complete renal response (CR) (OR : 1.07, p= 0.046) and higher SLEDAI-2K at tapering initiation (OR : 2.57, p= 0.008) were correlated with higher risk of renal flares during tapering. Persistent hydroxychloroquine use (≥2/3 of follow-up) (OR : 0.28, p= 0.08) and lower SLEDAI-2K 12 months before IS D/C (OR : 1.70, p= 0.013) decreased the risk of post-D/C flares. Adverse outcomes (>30% eGFR decline, chronic kidney disease, end-stage renal disease, death) at the end of follow-up (median124 months) were more frequent in patients with flares during IS tapering (53% vs 16%, p< 0.0038) but did not differ between IS D/C achievers and non-achievers. In proliferative LN, differences mirrored those in entire cohort, except for time to D/C, which occurred 20 months earlier in membranous vs proliferative LN (ß-coef=-19.8, p= 0.014). CONCLUSION: Earlier CR achievement and lower SLEDAI-2K at tapering initiation prevent flares during IS tapering, while persistent hydroxychloroquine use and lower SLEDAI-2K 12 months before IS D/C prevent post-D/C flares. Flares during tapering increase the risk of unfavorable long-term outcomes. Earlier IS D/C is feasible in membranous LN.

3.
Lupus ; 32(10): 1155-1163, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37499240

RESUMO

Lupus nephritis (LN) is a major course of morbidity and mortality in patients with systemic lupus erythematosus (SLE), best managed by a multidisciplinary group. To this end, we gathered a group of rheumatologists, nephrologists and a nephropathologist to review current evidence regarding diagnosis and management of LN. In this consensus paper, we summarize the key points from this meeting and provide practice guidelines for the management of kidney involvement in SLE, in view of emerging new data concerning novel agents approved recently. Renal biopsy is indispensable for the management of LN. Yet, important pearls and pitfalls need to be considered regarding indications and interpretation, which are summarized in informative tables. In new-onset LN, experts agreed that, although belimumab may be added from disease onset, patients with moderate to severe proliferative nephritis (defined as: NIH activity index > 5 plus ≥ 1 of the following: (i) NIH chronicity index > 2, (ii) proteinuria > 3 g/24 h, and (iii) increase in serum creatinine > 20%) may be more likely to benefit the most. In all other patients who have already started standard-of-care treatment with either mycophenolate mofetil (MMF) or cyclophosphamide (CY), belimumab could be considered in cases with an inadequate clinical response by 3 months, or in cases that experience a nephritic flare following initial response, or have an inability to reduce the dose of glucocorticoids. In all circumstances, the drug should be given as add-on therapy, that is, in combination with a standard-of-care therapy (MMF or CY). Voclosporin could be considered for up to 3 years, in combination with MMF, in patients with heavy proteinuria (well above the nephrotic range), wherein a quick reduction of protein loss in urine is desirable to avoid the complications of the nephrotic syndrome, either as part of the initial regimen, or in cases of inadequate reduction of proteinuria with MMF. In view of the potential scarring effects, long-term administration beyond the first year requires further documentation.


Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Ciclofosfamida/uso terapêutico , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Nefrite Lúpica/diagnóstico , Ácido Micofenólico/uso terapêutico , Proteinúria/etiologia , Resultado do Tratamento
4.
Transpl Int ; 36: 11507, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37901296

RESUMO

In our prospective, unicenter cohort study, we collected blood samples from 30 newly kidney transplanted patients, at month 1, 2, 3, and 5 for dd-cfDNA analysis, along with creatinine/eGFR and DSA monitoring, and from 32 patients who underwent an indication biopsy and whose dd-cfDNA levels were measured at the time of biopsy and 1 month afterwards. Fourteen of 32 (43.8%) patients in the biopsy group were diagnosed with TCMR and 5 of 32 (15.6%) with ABMR. Dd-cfDNA proved to be better than creatinine in diagnosing rejection from non-rejection in patients who were biopsied. When a dd-cfDNA threshold of 0.5% was chosen, sensitivity was 73.7% and specificity was 92.3% (AUC: 0.804, 0.646-0.961). In rejection patients, levels of dd-cfDNA prior to biopsy (0.94%, 0.3-2.0) decreased substantially after initiation of treatment with median returning to baseline already at 1 month (0.33%, 0.21-0.51, p = 0.0036). In the surveillance group, high levels of dd-cfDNA (>0.5%) from second month post-transplantation were correlated with non-increasing eGFR 1 year post-transplantation. The study used AlloSeq kit for kidney transplant surveillance for first time and confirmed dd-cfDNA's ability to detect rejection and monitor treatment, as well as to predict worse long-term outcomes regarding eGFR.


Assuntos
Ácidos Nucleicos Livres , Transplante de Rim , Humanos , Estudos de Coortes , Creatinina , Estudos Prospectivos
5.
Nephrol Dial Transplant ; 37(7): 1261-1269, 2022 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34850173

RESUMO

BACKGROUND: The nonsteroidal mineralocorticoid receptor antagonist finerenone and the sodium-glucose cotransporter-2 inhibitor (SGLT-2i) canagliflozin reduce cardiorenal risk in albuminuric patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). At first glance, the results of Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease (FIDELIO-DKD) (ClinicalTrials.gov, NCT02540993) and Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) appear disparate. In FIDELIO-DKD, the primary endpoint had an 18% [95% confidence interval (CI) 7-27] relative risk reduction; in CREDENCE, the primary endpoint had a 30% (95% CI 18-41) relative risk reduction. Unlike CREDENCE, the FIDELIO-DKD trial included patients with high albuminuria but excluded patients with symptomatic heart failure with reduced ejection fraction. The primary endpoint in the FIDELIO-DKD trial was kidney specific and included a sustained decline in the estimated glomerular filtration rate (eGFR) of ≥40% from baseline. In contrast, the primary endpoint in the CREDENCE trial included a sustained decline in eGFR of ≥57% from baseline and cardiovascular (CV) death. This post hoc exploratory analysis investigated how differences in trial design-inclusion/exclusion criteria and definition of primary outcomes-influenced observed treatment effects. METHODS: Patients from FIDELIO-DKD who met the CKD inclusion criteria of the CREDENCE study (urine albumin: creatinine ratio >300-5000 mg/g and an eGFR of 30-<90 mL/min/1.73 m2 at screening) were included in this analysis. The primary endpoint was a cardiorenal composite (CV death, kidney failure, eGFR decrease of ≥57% sustained for ≥4 weeks or renal death). Patients with symptomatic heart failure with reduced ejection fraction were excluded from FIDELIO-DKD. Therefore, in a sensitivity analysis, we further adjusted for the baseline prevalence of heart failure. RESULTS: Of 4619/5674 (81.4%) patients who met the subgroup inclusion criteria, 49.6% were treated with finerenone and 50.4% received placebo. The rate of the cardiorenal composite endpoint was 43.9/1000 patient-years with finerenone compared with 59.5/1000 patient-years with placebo. The relative risk was significantly reduced by 26% with finerenone versus placebo [hazard ratio (HR) 0.74 (95% CI 0.63-0.87)]. In CREDENCE, the rate of the cardiorenal composite endpoint was 43.2/1000 patient-years with canagliflozin compared with 61.2/1000 patient-years with placebo; a 30% risk reduction was observed with canagliflozin [HR 0.70 (95% CI 0.59-0.82)]. CONCLUSIONS: This analysis highlights the pitfalls of direct comparisons between trials. When key differences in trial design are considered, FIDELIO-DKD and CREDENCE demonstrate cardiorenal benefits of a similar magnitude.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Insuficiência Cardíaca , Insuficiência Renal Crônica , Inibidores do Transportador 2 de Sódio-Glicose , Canagliflozina/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Naftiridinas , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
6.
Clin Exp Rheumatol ; 40(4): 741-750, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35522540

RESUMO

OBJECTIVES: To explore the frequency and impact of an autoimmune disease past-medical history (PMH) in the clinical picture and outcomes of patients with antineutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis (AAV). METHODS: This was a retrospective study of patients with biopsy-proven AAV, >16 years old, with detailed information about their PMH. Outcomes of interest included remission, treatment resistance, relapse, end-stage kidney disease (ESKD), and death. RESULTS: 206 patients with biopsy-proven AAV and available information regarding their PMH were studied. 63(30.6%) of them had a history of autoimmune disease prior to AAV diagnosis. The mean age overall was 54.1 years. One hundred and five patients (51%) were positive for PR3-ANCA, 101 (49%) for MPO-ANCA. Granulomatosis with polyangiitis was diagnosed in 79 (38.3%), microscopic polyangiitis in 97 (47.1%) and renal-limited vasculitis in 30 (14.6%) individuals. Remission rate was similar among patients with and without a PMH of autoimmune disease. Time-to-event analysis indicated that the relapse-free survival was significantly longer in patients with PMH of autoimmune disease (148.2 vs. 61.9 months, p-value <0.001). After adjusting for covariates, autoimmune disease history was associated with significantly lower risk of relapse (HR: 0.33, 95% CI: 0.15-0.72), which remained significant in males, patients ≥60 years old and those with C/PR3-ANCA, kidney and lung involvement. CONCLUSIONS: Patients with a PMH of autoimmune disease, prior to AAV diagnosis, experienced significantly fewer relapses after achievement of remission, compared to patients without such a history, underlining the importance of individualisation of maintenance immunosuppressive therapy, given the different aetiopathogenetic settings the disease was developed.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Doenças Autoimunes , Granulomatose com Poliangiite , Nefropatias , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Anticorpos Anticitoplasma de Neutrófilos , Doenças Autoimunes/complicações , Feminino , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos
7.
Kidney Int ; 100(4): 881-893, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33964313

RESUMO

Outcomes relevant to treatment decision-making are inconsistently reported in trials involving glomerular disease. Here, we sought to establish a consensus-derived set of critically important outcomes designed to be reported in all future trials by using an online, international two-round Delphi survey in English. To develop this, patients with glomerular disease, caregivers and health professionals aged 18 years and older rated the importance of outcomes using a Likert scale and a Best-Worst scale. The absolute and relative importance was assessed and comments were analyzed thematically. Of 1198 participants who completed Round 1, 734 were patients/caregivers while 464 were health care professionals from 59 countries. Of 700 participants that completed Round 2, 412 were patients/caregivers and 288 were health care professionals. Need for dialysis or transplant, kidney function, death, cardiovascular disease, remission-relapse and life participation were the most important outcomes to patients/caregivers and health professionals. Patients/caregivers rated patient-reported outcomes higher while health care professionals rated hospitalization, death and remission/relapse higher. Four themes explained the reasons for their priorities: confronting death and compounded suffering, focusing on specific targets in glomerular disease, preserving meaning in life, and fostering self-management. Thus, consistent reporting of these critically important outcomes in all trials involving glomerular disease is hoped to improve patient-centered decision-making.


Assuntos
Cuidadores , Diálise Renal , Adulto , Técnica Delphi , Humanos , Avaliação de Resultados em Cuidados de Saúde , Inquéritos e Questionários
8.
Ann Rheum Dis ; 80(9): 1175-1182, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34162597

RESUMO

BACKGROUND: Quality of care is receiving increased attention in systemic lupus erythematosus (SLE). We developed quality indicators (QIs) for SLE based on the 2019 update of European League Against Rheumatism recommendations. METHODS: A total of 44 candidate QIs corresponding to diagnosis, monitoring and treatment, were independently rated for validity and feasibility by 12 experts and analysed by a modified Research and Development Corporation/University of California Los Angeles model. Adherence to the final set of QIs and correlation with disease outcomes (flares, hospitalisations and organ damage) was tested in a cohort of 220 SLE patients with a median monitoring of 2 years (IQR 2-4). RESULTS: The panel selected a total of 18 QIs as valid and feasible. On average, SLE patients received 54% (95% CI 52.3% to 56.2%) of recommended care, with adherence ranging from 44.7% (95% CI 40.8% to 48.6%) for diagnosis-related QIs to 84.3% (95% CI 80.6% to 87.5%) for treatment-related QIs. Sustained remission or low disease activity were achieved in 26.8% (95% CI 21.1% to 33.2%). Tapering of prednisone dose to less than 7.5 mg/day was achieved in 93.6% (95% CI 88.2% to 97.0%) while 73.5% (95% CI 66.6% to 79.6%) received the recommended hydroxychloroquine dose. Higher adherence to monitoring-related QIs was associated with reduced risk for a composite adverse outcome (flare, hospitalisation or damage accrual) during the last year of observation (OR 0.97 per 1% adherence rate, 95% CI 0.96 to 0.99). CONCLUSION: We developed QIs for assessing and improving the care of SLE patients. Initial real-life data suggest face validity, but a variable degree of adherence and a need for further improvement.


Assuntos
Lúpus Eritematoso Sistêmico/terapia , Indicadores de Qualidade em Assistência à Saúde , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Antirreumáticos/administração & dosagem , Aspirina/uso terapêutico , Redução da Medicação , Europa (Continente) , Feminino , Glucocorticoides/administração & dosagem , Fidelidade a Diretrizes/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Humanos , Hidroxicloroquina/administração & dosagem , Imunossupressores/uso terapêutico , Rim/patologia , Lúpus Eritematoso Sistêmico/diagnóstico , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/terapia , Masculino , Programas de Rastreamento , Osteoporose/diagnóstico , Inibidores da Agregação Plaquetária/uso terapêutico , Guias de Prática Clínica como Assunto , Pré-Eclâmpsia/prevenção & controle , Prednisona/administração & dosagem , Gravidez , Indução de Remissão , Reprodutibilidade dos Testes , Medição de Risco , Sociedades Médicas , Exacerbação dos Sintomas
9.
Clin Immunol ; 217: 108488, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32479988

RESUMO

B-cell clonal expansion has been sporadically described in the blood and/or renal tissue of patients with glomerulonephritides, albeit with unclear pathogenetic role. Herein, using spectratyping analysis, we observed oligoclonal intrarenal B-cell populations in 59% of glomerulonephritis patients with podocyte injury (6/7 with focal segmental glomerulosclerosis, 1/3 minimal change disease, 1/3 idiopathic membranous nephropathy, 3/4 IgA nephropathy, 2/5 membranous lupus nephritis), 20% of glomerulonephritis patients without podocyte involvement (4/13 with mesangial or proliferative lupus nephritis, 0/3 idiopathic membranoproliferative glomerulonephritis, 0/4 pauci-immune vasculitis) and 17% of control patients with renal cancer. In multivariate analysis, oligoclonal B-cells were associated with podocyte injury and the grade of glomerulosclerosis (both p = .009). B-cell oligoclonal expansions were not found in the paired peripheral blood samples. We postulate that B-cell expansion in the kidney results from local stimuli, including antigens expressed on podocytes. Further studies to unravel the role of oligoclonal B-cells in (auto)immune-mediated kidney disease are warranted.


Assuntos
Linfócitos B/patologia , Glomerulonefrite por IGA/imunologia , Glomerulonefrite Membranosa/imunologia , Glomerulosclerose Segmentar e Focal/imunologia , Cadeias Pesadas de Imunoglobulinas/imunologia , Nefrite Lúpica/imunologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Glomerulonefrite por IGA/patologia , Glomerulonefrite Membranosa/patologia , Glomerulosclerose Segmentar e Focal/patologia , Hematúria/patologia , Humanos , Neoplasias Renais/imunologia , Neoplasias Renais/patologia , Nefrite Lúpica/patologia , Masculino , Pessoa de Meia-Idade , Podócitos/patologia , Proteinúria/patologia
10.
Ann Rheum Dis ; 79(6): 713-723, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32220834

RESUMO

OBJECTIVE: To update the 2012 EULAR/ERA-EDTA recommendations for the management of lupus nephritis (LN). METHODS: Following the EULAR standardised operating procedures, a systematic literature review was performed. Members of a multidisciplinary Task Force voted independently on their level of agreeement with the formed statements. RESULTS: The changes include recommendations for treatment targets, use of glucocorticoids and calcineurin inhibitors (CNIs) and management of end-stage kidney disease (ESKD). The target of therapy is complete response (proteinuria <0.5-0.7 g/24 hours with (near-)normal glomerular filtration rate) by 12 months, but this can be extended in patients with baseline nephrotic-range proteinuria. Hydroxychloroquine is recommended with regular ophthalmological monitoring. In active proliferative LN, initial (induction) treatment with mycophenolate mofetil (MMF 2-3 g/day or mycophenolic acid (MPA) at equivalent dose) or low-dose intravenous cyclophosphamide (CY; 500 mg × 6 biweekly doses), both combined with glucocorticoids (pulses of intravenous methylprednisolone, then oral prednisone 0.3-0.5 mg/kg/day) is recommended. MMF/CNI (especially tacrolimus) combination and high-dose CY are alternatives, for patients with nephrotic-range proteinuria and adverse prognostic factors. Subsequent long-term maintenance treatment with MMF or azathioprine should follow, with no or low-dose (<7.5 mg/day) glucocorticoids. The choice of agent depends on the initial regimen and plans for pregnancy. In non-responding disease, switch of induction regimens or rituximab are recommended. In pure membranous LN with nephrotic-range proteinuria or proteinuria >1 g/24 hours despite renin-angiotensin-aldosterone blockade, MMF in combination with glucocorticoids is preferred. Assessment for kidney and extra-renal disease activity, and management of comorbidities is lifelong with repeat kidney biopsy in cases of incomplete response or nephritic flares. In ESKD, transplantation is the preferred kidney replacement option with immunosuppression guided by transplant protocols and/or extra-renal manifestations. Treatment of LN in children follows the same principles as adult disease. CONCLUSIONS: We have updated the EULAR recommendations for the management of LN to facilitate homogenization of patient care.


Assuntos
Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Sociedades Médicas , Antirreumáticos/uso terapêutico , Azatioprina/uso terapêutico , Inibidores de Calcineurina/uso terapêutico , Quimioterapia Combinada , Europa (Continente) , Taxa de Filtração Glomerular , Glucocorticoides/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Falência Renal Crônica/etiologia , Falência Renal Crônica/terapia , Nefrite Lúpica/complicações , Nefrite Lúpica/patologia , Nefrite Lúpica/fisiopatologia , Ácido Micofenólico/uso terapêutico , Proteinúria/etiologia , Proteinúria/terapia
11.
Transpl Infect Dis ; 22(6): e13442, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32780553

RESUMO

BACKGROUND: Kidney transplant recipients (KTRs) are at increased risk of infections. METHODS: The aims of this study were to describe the incidence of bloodstream infections (BSIs) by gram-negative bacteria in a cohort of KTRs, the risk factors for BSI due to multi-drug-resistant (MDR) gram-negative bacteria, and the predictors for unfavorable outcome, defined as death or nephrectomy or return to dialysis, within 30 days from BSI. We conducted a retrospective cohort study at the renal transplant unit of a tertiary care hospital in Athens, Greece. RESULTS: In a total of 1962 KTRs, we recorded 195 BSI episodes in 182 single patients (male/female = 97/85), with a median (interquartile range) age of 57.2 (44-64.9) years. The incidence was 1.393/100 patient-years. The most common source of infection was urinary tract (70.9%), and Escherichia coli (63.7%) was the most common pathogen. 19.2% of the infecting organisms were MDR; previous antibiotic use (OR 8.2; CI 2.1-32.9) and previous stay in the intensive care unit (OR 34.2; CI 1.6-730.2) were associated with MDR BSIs. 6% of patients died, and 2.2% underwent nephrectomy, while no patients had to return to dialysis. Diabetes mellitus (OR 8.1; 95% CI 1.3-50.3), Pseudomonas aeruginosa BSI (OR 46.1; 95% CI 3.9-552.3), and septic shock (OR 46.7; 95% CI 1.7-1304.9) were independent predictors of unfavorable outcome. CONCLUSION: Bloodstream infections in KTRs have a significant impact on allograft and patients outcome.


Assuntos
Bacteriemia , Infecções por Bactérias Gram-Negativas , Transplante de Rim , Sepse , Bacteriemia/epidemiologia , Feminino , Bactérias Gram-Negativas , Infecções por Bactérias Gram-Negativas/epidemiologia , Grécia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Sepse/epidemiologia , Transplantados
12.
BMC Nephrol ; 21(1): 351, 2020 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-32811472

RESUMO

BACKGROUND: Hypocomplementemic urticarial vasculitis syndrome is an infrequent condition characterized by ocular, renal, gastrointestinal and pulmonary involvement with low serum complement levels and autoantibodies. Renal manifestations vary from microscopic hematuria to nephrotic syndrome and acute kidney injury. Accordingly differing histologic patterns have been reported. CASE PRESENTATION: We present the case of a 65 years old woman with a history of chronic uveitis who presented with arthralgias, urticarial rush, nephrotic syndrome, glomerular hematuria and low serum complement. Kidney biopsy revealed an immune-complex membranoproliferative glomerulonephritis. The patient received induction therapy with steroids, cyclophosphamide and hydroxychloroquine followed by rapid clinical improvement and remission of proteinuria. Maintenance treatment consisted of rituximab pulses. CONCLUSIONS: The majority of hypocomplementemic urticarial vasculitis syndrome cases is idiopathic, although an association to drugs, infections or other autoimmune disorders has been recorded. Given the rarity and heterogeneity of the disease, no standard treatment is established.


Assuntos
Urticária Crônica/complicações , Proteínas do Sistema Complemento/metabolismo , Glomerulonefrite Membranoproliferativa/complicações , Síndrome Nefrótica/complicações , Uveíte/complicações , Vasculite/complicações , Idoso , Antirreumáticos/uso terapêutico , Artrite/complicações , Urticária Crônica/tratamento farmacológico , Urticária Crônica/metabolismo , Ciclofosfamida/uso terapêutico , Feminino , Glomerulonefrite Membranoproliferativa/tratamento farmacológico , Glomerulonefrite Membranoproliferativa/metabolismo , Glomerulonefrite Membranoproliferativa/patologia , Glucocorticoides/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Síndrome Nefrótica/tratamento farmacológico , Síndrome Nefrótica/metabolismo , Síndrome Nefrótica/patologia , Proteinúria/metabolismo , Rituximab/uso terapêutico , Uveíte/tratamento farmacológico , Uveíte/metabolismo , Vasculite/tratamento farmacológico , Vasculite/metabolismo
13.
Ann Rheum Dis ; 78(6): 736-745, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30926722

RESUMO

Our objective was to update the EULAR recommendations for the management of systemic lupus erythematosus (SLE), based on emerging new evidence. We performed a systematic literature review (01/2007-12/2017), followed by modified Delphi method, to form questions, elicit expert opinions and reach consensus. Treatment in SLE aims at remission or low disease activity and prevention of flares. Hydroxychloroquine is recommended in all patients with lupus, at a dose not exceeding 5 mg/kg real body weight. During chronic maintenance treatment, glucocorticoids (GC) should be minimised to less than 7.5 mg/day (prednisone equivalent) and, when possible, withdrawn. Appropriate initiation of immunomodulatory agents (methotrexate, azathioprine, mycophenolate) can expedite the tapering/discontinuation of GC. In persistently active or flaring extrarenal disease, add-on belimumab should be considered; rituximab (RTX) may be considered in organ-threatening, refractory disease. Updated specific recommendations are also provided for cutaneous, neuropsychiatric, haematological and renal disease. Patients with SLE should be assessed for their antiphospholipid antibody status, infectious and cardiovascular diseases risk profile and preventative strategies be tailored accordingly. The updated recommendations provide physicians and patients with updated consensus guidance on the management of SLE, combining evidence-base and expert-opinion.


Assuntos
Lúpus Eritematoso Sistêmico/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Comorbidade , Gerenciamento Clínico , Medicina Baseada em Evidências/métodos , Glucocorticoides/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Índice de Gravidade de Doença
14.
Histopathology ; 75(5): 660-671, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31318463

RESUMO

AIMS: Diagnosis of primary membranous nephropathy (PMN) is mainly based on immunofluorescence/immunohistochemistry findings. However, assessment of specific features on optical microscopy can help to estimate the severity of the disease, guide treatment and predict the response. The aim of this study was to identify, classify and grade the precise histological findings in PMN to predict renal function outcome and guide treatment. METHODS AND RESULTS: Histological parameters, including focal segmental sclerosis (FSGS), tubular atrophy (TA), interstitial fibrosis (IF) and vascular hyalinosis (VH), were re-evaluated in 752 patients with PMN. Their predictive value was estimated separately, and also in a combination score (FSTIV) graded from 0 to 4. Finally, the impact of histology was assessed in the response to immunosuppressive treatment. Mean age of patients was 53.3 (15-85) years and most presented with nephrotic syndrome. FSGS was present in 32% and VH in 51% of the patients, while TA and IF were graded as stage ≥1 in 52% and 51.4%, respectively. The follow-up period was 122.3 (112-376) months. FSGS, TA and IF and VH were associated with impaired renal function at diagnosis (P = 0.02, P < 0.0001, P = 0.001 and P = 0.02, respectively) and at the end of follow-up (P = 0.004, P < 0.0001, P < 0.0001 and P = 0.04, respectively). In multiple regression and binary logistic analysis, the presence of FSGS and degree of TA were the most significant parameters predicting renal function outcome, defined either by eGFR (end), FSGS (r = 0.6, P < 0.0001) and TA (r = 0.6, P < 0.0001), or by the endpoint of >50% eGFR reduction, FSGS (P = 0.001) and TA (P = 0.02). Also, patients presented with FSGS, IF, VH and/or with FSTIV > 1 could benefit from immunosuppression, regardless of clinical presentation. CONCLUSIONS: The presence and degree of four histological indices, FSGS, VH, TA and IF, assessed separately or in combination, and FSTIV score not only predict renal function outcome after long-term follow-up, but can also help in the choice of appropriate treatment. Decisions concerning immunosuppressive treatment can be guided by pathology regardless of clinical findings.


Assuntos
Glomerulonefrite Membranosa , Nefropatias/patologia , Rim/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Feminino , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/patologia , Glomerulonefrite Membranosa/terapia , Histocitoquímica , Humanos , Imunossupressores/uso terapêutico , Nefropatias/diagnóstico , Nefropatias/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Adulto Jovem
15.
Medicina (Kaunas) ; 55(7)2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31336742

RESUMO

Acute kidney injury in the context of nephrotic syndrome is a serious and alarming clinical problem. Largely, acute kidney injury is a relatively frequent complication among patients with comorbidities while it has been independently associated with an increased risk of adverse outcomes, including death and chronic kidney disease. Nephrotic syndrome, without hematuria or with minimal hematuria, includes a list of certain glomerulopathies; minimal change disease, focal segmental glomerulosclerosis and membranous nephropathy. In the light of primary nephrotic syndrome, pathophysiology of acute kidney injury is differentiated by the nature of the primary disease and the severity of the nephrotic state. This review aims to explore the clinical circumstances and pathogenetic mechanisms of acute kidney injury in patients with nephrotic syndrome due to primary glomerulopathies, focusing on newer perceptions regarding the pathogenesis and management of this complicated condition, for the prompt recognition and timely initiation of appropriate treatment in order to restore renal function to its baseline level. Prompt recognition of the precise cause of acute kidney injury is crucial for renal recovery. Clinical characteristics, laboratory and serological findings along with histopathological findings, if required, will reveal the implicated pathway leading to individualized approach and management.


Assuntos
Injúria Renal Aguda/etiologia , Rim/patologia , Síndrome Nefrótica/complicações , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/fisiopatologia , Anticoagulantes/efeitos adversos , Anticoagulantes/farmacologia , Anticoagulantes/uso terapêutico , Biópsia/instrumentação , Biópsia/métodos , Inibidores de Calcineurina/efeitos adversos , Inibidores de Calcineurina/uso terapêutico , Glomerulosclerose Segmentar e Focal/etiologia , Glomerulosclerose Segmentar e Focal/fisiopatologia , Humanos , Rim/metabolismo , Rim/fisiopatologia , Nefrite Intersticial/etiologia , Nefrite Intersticial/fisiopatologia , Síndrome Nefrótica/fisiopatologia , Veias Renais/patologia , Veias Renais/fisiopatologia , Trombose/etiologia , Trombose/fisiopatologia , Varfarina/efeitos adversos , Varfarina/farmacologia , Varfarina/uso terapêutico
16.
J Cell Mol Med ; 22(9): 4139-4149, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29956451

RESUMO

Chronic kidney disease, the end result of most renal and some systemic diseases, is a common condition where renal function is compromised due to fibrosis. During renal fibrosis, calreticulin, a multifunctional chaperone of the endoplasmic reticulum (ER) is up-regulated in tubular epithelial cells (TECs) both in vitro and in vivo. Proteomic analysis of cultured TECs overexpressing calreticulin led to the identification of the family of 14-3-3 proteins as key proteins overexpressed as well. Furthermore, an increased expression in the majority of 14-3-3 family members was observed in 3 different animal models of renal pathologies: the unilateral ureteric obstruction, the nephrotoxic serum administration and the ischaemia-reperfusion. In all these models, the 14-3-3σ isoform (also known as stratifin) was predominantly overexpressed. As in all these models ischaemia is a common denominator, we showed that the ischaemia-induced transcription factor HIF1α is specifically associated with the promoter region of the 14-3-3σ gene. Finally, we evaluated the expression of the family of 14-3-3 proteins and specifically 14-3-3σ in biopsies from IgA nephropathy and membranous nephropathy patients. These results propose an involvement of 14-3-3σ in renal pathology and provide evidence for the first time that hypoxia may be responsible for its altered expression.


Assuntos
Proteínas 14-3-3/genética , Biomarcadores Tumorais/genética , Exorribonucleases/genética , Glomerulonefrite por IGA/genética , Glomerulonefrite Membranosa/genética , Insuficiência Renal Crônica/genética , Traumatismo por Reperfusão/genética , Obstrução Ureteral/genética , Proteínas 14-3-3/metabolismo , Animais , Biomarcadores Tumorais/metabolismo , Calreticulina/genética , Calreticulina/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Exorribonucleases/metabolismo , Fibrose , Regulação da Expressão Gênica , Glomerulonefrite por IGA/metabolismo , Glomerulonefrite por IGA/patologia , Glomerulonefrite Membranosa/metabolismo , Glomerulonefrite Membranosa/patologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Isoenzimas/genética , Isoenzimas/metabolismo , Túbulos Renais/metabolismo , Túbulos Renais/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Regiões Promotoras Genéticas , Proteômica/métodos , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Transdução de Sinais , Obstrução Ureteral/metabolismo , Obstrução Ureteral/patologia
17.
Clin Exp Rheumatol ; 35 Suppl 103(1): 155-164, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28134075

RESUMO

OBJECTIVES: To evaluate the long-term outcomes of patients with multi-relapsing antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), who received sequentially therapy with cyclophosphamide and rituximab, upon new onset of aggressive vasculitis. METHODS: We retrospectively studied patients with multiple-relapsing AAV, who were treated with the standard regimen plus rituximab, given in sequence, upon a major relapse, compared to historical patients, who had been treated with the standard regimen alone in the same setting. The main outcomes of interest were relapse rates and frequency of adverse events. RESULTS: Of 147 patients with biopsy proven AAV, 35 (23.8%) experienced at least one major relapse, of whom, 14 (9.5%) received the sequential regimen and were compared to 21 (14.3%) historic patients, who had received the standard regimen alone for the same reason. Patients in both groups achieved remission in similar rates, but those treated with the sequential regimen experienced a significant decline in the relapse rate afterwards, compared to their corresponding rate prior to study entry [0.07 episodes of relapse per patient-year (95%CI: 0.03-0.2) vs. 0.38 (95%CI: 0.35-0.60) respectively, (p=0.004)]. The need for cyclophosphamide was significantly decreased in patients in whom cyclophosphamide was followed by rituximab [3.3(0-10.5) grams vs. 14.5 (4-177) grams, (p<0.0001)] but not in controls [17.2(0-108) grams vs. 14.5(0-63) grams, p=0.61]. CONCLUSIONS: Our data show that sequential therapy with cyclophosphamide and rituximab, upon a major relapse, in patients with frequently relapsing AAV, is associated with prolonged remission, allowing minimization of the ultimate exposure to cyclophosphamide.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Anticorpos Anticitoplasma de Neutrófilos/sangue , Ciclofosfamida/administração & dosagem , Imunossupressores/administração & dosagem , Rituximab/administração & dosagem , Adolescente , Adulto , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/sangue , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Biomarcadores/sangue , Ciclofosfamida/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Recidiva , Sistema de Registros , Indução de Remissão , Estudos Retrospectivos , Rituximab/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
18.
J Autoimmun ; 72: 57-64, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27194577

RESUMO

OBJECTIVES: Prompt, aggressive therapy is vital for anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis. In this regard, we aimed to identify predictors of distinct renal histopathological classes at the time of clinical diagnosis. PATIENTS & METHODS: An inception cohort of patients with biopsy proven ANCA-associated glomerulonephritis was studied retrospectively. Demographics, clinical, laboratory, serological and radiological parameters were analyzed. Patients were classified on the basis of renal histopathology. A risk score was developed for each histopathological class using univariate and stepwise logistic regression analyses. RESULTS: Variables independently associated with focal class included disease duration up to diagnosis <8 weeks, absence of erythrocyte casts by urine microscopy and eGFR >49 ml/min/1.73 m(2); with crescentic class >40 erythrocytes/hpf, identification of erythrocyte casts in urine, upper respiratory tract involvement and eGFR <49 ml/min/1.73 m(2); with mixed class age >54 years, male gender, and absence of upper respiratory tract involvement. In the presence of these risk factors a predictive risk score for each histopathological classes was calculated: odds ratio, 95% confidence intervals (CI), for focal class (≥2 risk factors, 20.8 (95% CI: 5.1-84.2), p < 0.0001, and 441.0 (95% CI: 16.8-11,590), p = 0.0003 for crescentic class (≥3 risk factors) while the small number of patients in the mixed and sclerotic class precluded any estimates. CONCLUSION: We propose a predictive algorithm of specific histolopathological classes of ANCA-associated glomerulonephritis, which might provide a crude estimation of the disease activity in the glomeruli at presentation. This tool might assist the clinician in making decisions regarding the level of intensity of inductive immunosuppressive therapy at clinical diagnosis.


Assuntos
Anticorpos Anticitoplasma de Neutrófilos/imunologia , Glomerulonefrite/imunologia , Nefropatias/imunologia , Rim/imunologia , Adulto , Idoso , Análise de Variância , Biópsia , Feminino , Glomerulonefrite/complicações , Glomerulonefrite/terapia , Humanos , Rim/patologia , Nefropatias/complicações , Nefropatias/patologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Prognóstico , Estudos Retrospectivos , Fatores de Risco
19.
Ren Fail ; 37(5): 777-83, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25715638

RESUMO

OBJECTIVES: To explore the role of immunoadsorption (IA) for the treatment of idiopathic focal segmental glomerulosclerosis (FSGS) recurrence in the renal allograft, if applied in a personalized manner. METHODS: We studied patients with end-stage renal disease (ESRD) due to idiopathic FSGS, transplanted between 2001 and 2010. Patients with FSGS recurrence were treated with daily sessions of IA for the first week, followed by an every other day scheme and then individualized tapering until discontinuation. Complete remission was defined as a reduction of 24-h proteinuria to ≤ 0.5 g/day and partial remission as a reduction of 24-h proteinuria to 50% or more from baseline. RESULTS: Of the 18 renal transplant recipients with ESRD due to idiopathic FSGS, 12 (66.7%) experienced disease recurrence in a mean time of 0.75 months post-transplantation (KTx), with a mean proteinuria of 8.9 g/day at the time of recurrence. The mean recipient age was 30.8 years; the mean donor age was 47.4 years, while living related donors provided the allograft in seven cases. Four of the patients received therapy with rituximab in addition to IA. During a mean time of follow-up of 48.3 months, seven patients (58.3%) achieved complete remission, and five (41.7%) partial remission. At the end of follow-up, eight patients (66.7%) had functioning grafts, being in sustained remission, in contrast to four patients (33.3%), who ended up in ESRD because of FSGS recurrence. CONCLUSIONS: IA was shown efficacious in a small series of patients with recurrent FSGS in the graft. Renal function remained stable in eight of the 12 patients with FSGS recurrence.


Assuntos
Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Imunossupressores/uso terapêutico , Falência Renal Crônica/cirurgia , Transplante de Rim/métodos , Proteinúria/tratamento farmacológico , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Plasmaferese/métodos , Recidiva , Indução de Remissão , Rituximab/uso terapêutico , Doadores de Tecidos , Adulto Jovem
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