RESUMEN
Membranous nephropathy (MN) is a leading cause of kidney failure worldwide and frequently recurs after transplant. Available data originated from small retrospective cohort studies or registry analyses; therefore, uncertainties remain on risk factors for MN recurrence and response to therapy. Within the Post-Transplant Glomerular Disease Consortium, we conducted a retrospective multicenter cohort study examining the MN recurrence rate, risk factors, and response to treatment. This study screened 22,921 patients across 3 continents and included 194 patients who underwent a kidney transplant due to biopsy-proven MN. The cumulative incidence of MN recurrence was 31% at 10 years posttransplant. Patients with a faster progression toward end-stage kidney disease were at higher risk of developing recurrent MN (hazard ratio [HR], 0.55 per decade; 95% confidence interval [CI], 0.35-0.88). Moreover, elevated pretransplant levels of anti-phospholipase A2 receptor (PLA2R) antibodies were strongly associated with recurrence (HR, 18.58; 95% CI, 5.37-64.27). Patients receiving rituximab for MN recurrence had a higher likelihood of achieving remission than patients receiving renin-angiotensin-aldosterone system inhibition alone. In sum, MN recurs in one-third of patients posttransplant, and measurement of serum anti-PLA2R antibody levels shortly before transplant could aid in risk-stratifying patients for MN recurrence. Moreover, patients receiving rituximab had a higher rate of treatment response.
Asunto(s)
Glomerulonefritis Membranosa , Trasplante de Riñón , Recurrencia , Humanos , Glomerulonefritis Membranosa/etiología , Glomerulonefritis Membranosa/patología , Glomerulonefritis Membranosa/tratamiento farmacológico , Trasplante de Riñón/efectos adversos , Masculino , Estudios Retrospectivos , Femenino , Persona de Mediana Edad , Factores de Riesgo , Estudios de Seguimiento , Pronóstico , Adulto , Tasa de Filtración Glomerular , Fallo Renal Crónico/cirugía , Complicaciones Posoperatorias , Supervivencia de Injerto , Pruebas de Función Renal , Incidencia , Rechazo de Injerto/etiología , Rechazo de Injerto/patología , Tasa de SupervivenciaRESUMEN
The optimal immunosuppressive regimen for recipients of expanded criteria donor (ECD) kidneys has not been identified. In this single-center study, 171 recipients of ECD kidney transplants were randomized to receive antithymocyte globulin induction, and delayed introduction of reduced dose tacrolimus, prednisone and everolimus (r-ATG/EVR, n = 88), or mycophenolate (r-ATG/MPS, n = 83). No cytomegalovirus (CMV) pharmacological prophylaxis was used. The primary endpoint was the incidence of CMV infection/disease at 12 months. Secondary endpoints included treatment failure [first biopsy-proven acute rejection (BPAR), graft loss, or death] and safety. Patients treated with EVR showed a 89% risk reduction (13.6 vs. 71.6%; HR 0.11, 95% CI 0.06-0.220, P < 0.001) in the incidence of first CMV infection/disease. Incidences of BPAR (16% vs. 5%, P = 0.021), graft loss (11% vs. 1%, P = 0.008), death (10% vs. 1%, P = 0.013), and treatment discontinuation (40% vs. 28%, P = 0.12) were higher in the r-ATG/EVR, leading to premature study termination. Mean glomerular filtration rate was lower in r-ATG/EVR (31.8 ± 18.8 vs. 42.6 ± 14.9, P < 0.001). In recipients of ECD kidney transplants receiving no CMV pharmacological prophylaxis, the use of everolimus was associated with higher treatment failure compared with mycophenolate despite the significant reduction in the incidence of CMV infection/disease (ClinicalTrials.gov.NCT01895049).
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Suero Antilinfocítico/administración & dosificación , Selección de Donante/métodos , Everolimus/administración & dosificación , Fallo Renal Crónico/cirugía , Trasplante de Riñón/métodos , Ácido Micofenólico/administración & dosificación , Anciano , Infecciones por Citomegalovirus/prevención & control , Funcionamiento Retardado del Injerto , Selección de Donante/normas , Femenino , Tasa de Filtración Glomerular , Rechazo de Injerto , Humanos , Terapia de Inmunosupresión , Inmunosupresores/uso terapéutico , Incidencia , Riñón/cirugía , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Tacrolimus/administración & dosificación , Resultado del TratamientoRESUMEN
AIM: Focal segmental glomerulosclerosis recurs in up to 30% and up to 80% of adult and pediatric kidney transplant recipients, respectively. There is no standard of care treatment. The purpose of this study was to evaluate clinical characteristics, treatments and outcomes of patients with focal segmental glomerulosclerosis recurrence (FSGSr). METHODS: This was a retrospective single-center cohort study including FSGSr patients treated with plasmapheresis (PP) and combinations of high dose steroids, cyclosporine and rituximab. RESULTS: Among 61 patients included in this analysis the median time to diagnosis was 19 days. The incidence of first biopsy-confirmed FSGSr was 18% reaching 52.4% with follow-up biopsies. During PP treatment 54% of the patients developed infectious complications. PP was discontinued in 37% of patients due to treatment failure (no remission or graft loss) and in 26% due to an adverse event. All patients who discontinued PP due to adverse event did not show clinical response or lost the allograft. The incidence of acute rejection was 34.4%. The incidences of partial and complete remissions were 16.4% and 27.8%, respectively. Overall 6-years patient and graft survivals were 90.7% and 64.5%, respectively. CONCLUSION: This analysis confirms the low, variable and unpredictable rate of FSGSr remission, inconsistencies among available therapeutic options and its high rate of adverse events, and the negative impact on graft survival.
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Glomeruloesclerosis Focal y Segmentaria/epidemiología , Trasplante de Riñón , Adolescente , Adulto , Niño , Femenino , Glomeruloesclerosis Focal y Segmentaria/terapia , Rechazo de Injerto/epidemiología , Supervivencia de Injerto , Humanos , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Plasmaféresis/efectos adversos , Recurrencia , Estudios Retrospectivos , Adulto JovenRESUMEN
INTRODUCTION: Several studies and meta-analysis suggest the mTOR inhibitors are associated with reduced incidence of CMV infection after kidney transplantation, although their effects on the high-risk population have not been investigated thoroughly. OBJECTIVE: This retrospective cohort study investigates the association between immunosuppression and CMV infection in D+/R- kidney transplant recipients receiving preemptive therapy. METHODS: All patients received rabbit anti-thymocyte globulin, tacrolimus, prednisone and azathioprine (AZA), mycophenolate (MPA) or everolimus (EVR). RESULTS: Among 89 D+R-, the overall incidence of CMV infection was 76%, with no difference among the groups AZA vs MPA vs EVR (73 vs 83 vs 74%, P = 0.643). CMV infection occurred later (31 in AZA vs 31 in MPA vs 43 days in EVR group, P < 0.001) and showed a lower trend of recurrences (57% in AZA vs 79% in MPA vs 48% in EVR group, P = 0.058) in the everolimus group. There were no differences in the IgG seroconversion rate (82% in AZA vs 76% in MPA vs 72% in EVR group, P = 0.983). There were no differences in the incidence of biopsy-proven acute rejection (10% in AZA vs 8% in MPA vs 6% in EVR group, P = 0.811) and renal function at 12 months (53.6 in AZA vs 60.3 in MPA vs. 55.4 mL/min/1.73 m2 in EVR group). CONCLUSION: In this cohort of high-risk CMV D+/R- kidney transplant recipients receiving rATG induction and tacrolimus, the use of mTOR inhibitors could only show a tendency towards but not a significant difference on the incidence of CMV events, when compared to antimetabolites.
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Infecciones por Citomegalovirus/epidemiología , Citomegalovirus/aislamiento & purificación , Inmunosupresores/efectos adversos , Trasplante de Riñón/efectos adversos , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Adulto , Anciano , Antivirales/uso terapéutico , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/transmisión , Infecciones por Citomegalovirus/virología , Femenino , Rechazo de Injerto/prevención & control , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Pruebas Serológicas , Donantes de Tejidos , Adulto JovenRESUMEN
BACKGROUND: Long-term outcomes in kidney transplantation (KT) have not significantly improved during the past twenty years. Despite being a leading cause of graft failure, glomerular disease (GD) recurrence remains poorly understood, due to heterogeneity in disease pathogenesis and clinical presentation, reliance on histopathology to confirm disease recurrence, and the low incidence of individual GD subtypes. Large, international cohorts of patients with GD are urgently needed to better understand the disease pathophysiology, predictors of recurrence, and response to therapy. METHODS: The Post-TrANsplant GlOmerular Disease (TANGO) study is an observational, multicenter cohort study initiated in January 2017 that aims to: 1) characterize the natural history of GD after KT, 2) create a biorepository of saliva, blood, urine, stools and kidney tissue samples, and 3) establish a network of patients and centers to support novel therapeutic trials. The study includes 15 centers in America and Europe. Enrollment is open to patients with biopsy-proven GD prior to transplantation, including IgA nephropathy, membranous nephropathy, focal and segmental glomerulosclerosis, atypical hemolytic uremic syndrome, dense-deposit disease, C3 glomerulopathy, complement- and IgG-positive membranoproliferative glomerulonephritis or membranoproliferative glomerulonephritis type I-III (old classification). During phase 1, patient data will be collected in an online database. The biorepository (phase 2) will involve collection of samples from patients for identification of predictors of recurrence, biomarkers of disease activity or response to therapy, and novel pathogenic mechanisms. Finally, through phase 3, we will use our multicenter network of patients and centers to launch interventional studies. DISCUSSION: Most prior studies of post-transplant GD recurrence are single-center and retrospective, or rely upon registry data that frequently misclassify the cause of kidney disease. Systematically determining GD recurrence rates and predictors of clinical outcomes is essential to improving post-transplant outcomes. Furthermore, accurate molecular phenotyping and biomarker development will allow better understanding of individual GD pathogenesis, and potentially identify novel drug targets for GD in both native and transplanted kidneys. The TANGO study has the potential to tackle GD recurrence through a multicenter design and a comprehensive biorepository.
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Glomerulonefritis/epidemiología , Internacionalidad , Trasplante de Riñón/efectos adversos , Complicaciones Posoperatorias/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Glomerulonefritis/diagnóstico , Glomerulonefritis/terapia , Humanos , Trasplante de Riñón/tendencias , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/terapia , Sistema de Registros , Adulto JovenRESUMEN
BACKGROUND: This analysis compared efficacy, renal function, and histology in kidney transplant recipients receiving tacrolimus (TAC) combined with everolimus (EVR) or mycophenolate (MPS). METHODS: This was a retrospective analysis from a randomized trial in kidney transplant recipients who received a single 3 mg/kg dose of rabbit antithymocyte globulin (r-ATG), TAC, EVR, and prednisone (PRED; r-ATG/EVR, n = 85), basiliximab (BAS), TAC, EVR, and PRED (BAS/EVR, n = 102) or BAS, TAC, MPS, and PRED (BAS/MPS, n = 101). We evaluated the incidence of de novo donor-specific anti-human leukocyte antigens antibodies (DSA) and histology on protocol biopsies at 12 months, and the incidence of acute rejection, estimated glomerular filtration rate (eGFR) and proteinuria at 36 months. RESULTS: At 12 months, there were no differences in de novo DSA (6.4 vs. 3.4 vs. 5.5%) or in subclinical inflammation (2.0 vs. 4.8 vs. 10.2%), interstitial fibrosis/tubular atrophy (57.1 vs. 58.5 vs. 53.8%) and C4d deposition (2.0 vs. 7.3 vs. 2.6%). At 36 months, there were no differences in the incidence of treatment failure (19.0 vs. 27.7 vs. 27.7%, p = 0.186), first biopsy-proven acute rejection (9.5 vs. 21.8 vs. 16.8%, p = 0.073), and urine protein/creatinine ratios (0.53 ± 1.05 vs. 0.62 ± 0.75 vs. 0.71 ± 1.24). eGFR was lower in the BAS/EVR compared to that in the BAS/MPS group (53.4 ± 20.9 vs. 50.8 ± 19.5 vs. 60.7 ± 21.2 mL/min/1.73 m2, p = 0.017) but comparable using a sensitive analysis (49.5 ± 23 vs. 47.5 ± 22.6 vs. 53.6 ± 27.8 mL/min/1.73 m2, p = 0.207). CONCLUSION: In this cohort, the use of EVR and reduced TAC concentrations were associated with comparable efficacy, renal function, and histological parameters compared to the standard-of-care immunosuppressive regimen.
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Rechazo de Injerto/prevención & control , Supervivencia de Injerto/efectos de los fármacos , Antígenos HLA/inmunología , Inmunosupresores/uso terapéutico , Fallo Renal Crónico/terapia , Trasplante de Riñón/efectos adversos , Adulto , Aloinjertos/inmunología , Aloinjertos/patología , Anticuerpos Monoclonales/uso terapéutico , Suero Antilinfocítico/uso terapéutico , Basiliximab , Biopsia , Quimioterapia Combinada/métodos , Everolimus/uso terapéutico , Femenino , Tasa de Filtración Glomerular , Rechazo de Injerto/epidemiología , Rechazo de Injerto/inmunología , Rechazo de Injerto/patología , Humanos , Riñón/inmunología , Riñón/patología , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Ácido Micofenólico/uso terapéutico , Prednisona/uso terapéutico , Estudios Prospectivos , Proteínas Recombinantes de Fusión/uso terapéutico , Estudios Retrospectivos , Tacrolimus/uso terapéutico , Donantes de Tejidos , Insuficiencia del Tratamiento , Resultado del Tratamiento , Privación de Tratamiento/estadística & datos numéricos , Adulto JovenRESUMEN
BACKGROUND: This study evaluated the influence of pharmaceutical care (PhC) in the intra-individual variability of dose-corrected whole blood tacrolimus (TAC) trough concentrations, adherence to immunosuppressive therapy and clinical outcomes. METHODS: We randomized 128 kidney transplant recipients to receive PhC consisted of predefined instructions provided by a pharmacist (PhC group, n = 64) or standard nurse staff instructions (control group, n = 64) from day 3 to day 90 after kidney transplantation. The study was powered to detect at least 50% reduction in the coefficient of variation (%CV), calculated from 6 dose-corrected whole blood TAC trough concentrations, in the PhC group. Patient adherence was evaluated using Basel Assessment of Adherence to Immunosuppressive Medication Scale (BAASIS) questionnaire. RESULTS: There was no difference in the %CV comparing PhC and control group (31.4% ± 12.3% versus 32.5% ± 16.1%, P = 0.673). There were no differences in the proportion of patients showing TAC concentrations within predefined target concentrations in each study visit. There was no difference in the proportion of nonadherent patients at day 28 (17% versus 26%, P = 0.135) and day 90 (27% versus 25%, P = 0.457) based on BAASIS questionnaire answers, respectively. There were no differences in clinical outcomes. CONCLUSIONS: Universal PhC in addition to standard nurse staff instruction was not associated with reduced intra-individual variability of dose-corrected whole blood TAC trough concentrations or improved adherence.
Asunto(s)
Inmunosupresores/sangre , Tacrolimus/sangre , Adulto , Esquema de Medicación , Femenino , Rechazo de Injerto/prevención & control , Humanos , Terapia de Inmunosupresión/métodos , Inmunosupresores/uso terapéutico , Trasplante de Riñón/métodos , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Servicios Farmacéuticos , Estudios Prospectivos , Tacrolimus/uso terapéutico , Receptores de TrasplantesRESUMEN
OBJECTIVE: To establish the occurrence and intensity of podocyturia and its relation to grade of disease activity, as defined by clinical and laboratory criteria. METHODS: Prospective, cross-sectional study involving 50 patients with lupus nephritis and 29 controls, which had podocyturia levels determined from random urine samples using an immunofluorescence technique. Disease activity was graded by BILAG (renal criteria) and an additional system used in the service (S2). RESULTS: Fifty patients with lupus nephritis (WHO classes III, IV and V), with a median age of 37 years, were evaluated. Of these, 86.5% were female, and 52% were BILAG A. Podocyturia quantification in the lupus nephritis and control groups differed significantly (p = 0.009). This score was higher in relation to classes III, IV and V. The correlation with C3 consumption was stronger (p = 0.011) than with C4. The highest levels were found in the most active groups (A and B of BILAG and S2). Lower podocyturia correlated with a lower dose of prednisone. There was no association with the intensity of proteinuria, hematuria or pyuria, serum creatinine levels, among others. CONCLUSIONS: Podocyturia assessment, which was performed by immunofluorescence in this study, can be used as an indicator of disease activity with the advantage of being a urinary biomarker. The levels proved to be higher in patients with lupus nephritis than in the controls and were particularly higher in class IV.
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Nefritis Lúpica/orina , Podocitos , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Orina/citología , Adulto JovenRESUMEN
Background: There is no consensus on the ideal strategy to treat posttransplant focal segmental glomerulosclerosis. The multiple-target therapy, which consisted of high-dose intravenous cyclosporine, prednisone, and plasmapheresis, showed favorable results. Methods: This single-center, prospective study sought to evaluate the multiple-target therapy in an independent cohort of patients. Results: Thirteen patients with posttransplant focal segmental glomerulosclerosis received multiple-target therapy. Complete remission was achieved in 2 patients (15.4%), and partial remission in another 2 patients (15.4%). Four patients (30.7%) did not show remission, and 5 patients (38%) lost the graft because of posttransplant focal segmental glomerulosclerosis during the 12-mo follow-up. Premature discontinuation of treatment occurred in 10 patients (77%), all associated with infectious adverse events. Cytomegalovirus was the most common complication, and preemptive therapy was used instead of prophylaxis. Conclusions: In this cohort of patients, the efficacy of the multiple-target therapy was poor and limited by the high incidence of infectious adverse events.
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BACKGROUND AND OBJECTIVES: In patients with kidney failure due to IgA nephropathy, IgA deposits can recur in a subsequent kidney transplant. The incidence, effect, and risk factors of IgA nephropathy recurrence is unclear, because most studies have been single center and sample sizes are relatively small. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a multicenter, international, retrospective study to determine the incidence, risk factors, and treatment response of recurrent IgA nephropathy after kidney transplantation. Data were collected from all consecutive patients with biopsy-proven IgA nephropathy transplanted between 2005 and 2015, across 16 "The Post-Transplant Glomerular Disease" study centers in Europe, North America, and South America. RESULTS: Out of 504 transplant recipients with IgA nephropathy, recurrent IgA deposits were identified by kidney biopsy in 82 patients; cumulative incidence of recurrence was 23% at 15 years (95% confidence interval, 14 to 34). Multivariable Cox regression revealed a higher risk for recurrence of IgA deposits in patients with a pre-emptive kidney transplant (hazard ratio, 3.45; 95% confidence interval, 1.31 to 9.17) and in patients with preformed donor-specific antibodies (hazard ratio, 2.59; 95% confidence interval, 1.09 to 6.19). After kidney transplantation, development of de novo donor-specific antibodies was associated with subsequent higher risk of recurrence of IgA nephropathy (hazard ratio, 6.65; 95% confidence interval, 3.33 to 13.27). Immunosuppressive regimen was not associated with recurrent IgA nephropathy in multivariable analysis, including steroid use. Graft loss was higher in patients with recurrence of IgA nephropathy compared with patients without (hazard ratio, 3.69; 95% confidence interval, 2.04 to 6.66), resulting in 32% (95% confidence interval, 50 to 82) graft loss at 8 years after diagnosis of recurrence. CONCLUSIONS: In our international cohort, cumulative risk of IgA nephropathy recurrence increased after transplant and was associated with a 3.7-fold greater risk of graft loss.
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Anticuerpos/sangre , Glomerulonefritis por IGA/epidemiología , Fallo Renal Crónico/etiología , Fallo Renal Crónico/cirugía , Adulto , Aloinjertos/inmunología , Aloinjertos/patología , Biopsia , Brasil/epidemiología , Europa (Continente)/epidemiología , Femenino , Glomerulonefritis por IGA/complicaciones , Glomerulonefritis por IGA/tratamiento farmacológico , Glomerulonefritis por IGA/patología , Supervivencia de Injerto , Humanos , Incidencia , Riñón/patología , Trasplante de Riñón , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND AND OBJECTIVES: FSGS recurrence after kidney transplantation is a major risk factor for graft loss. However, the natural history, clinical predictors, and response to treatment remain unclear because of small sample sizes and poor generalizability of single-center studies, and disease misclassification in registry-based studies. We therefore aimed to determine the incidence, predictors, and treatment response of recurrent FSGS in a large cohort of kidney transplant recipients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Post-Transplant Glomerular Disease (TANGO) project is an observational, multicenter, international cohort study that aims to investigate glomerular disease recurrence post-transplantation. Transplant recipients were screened for the diagnosis of idiopathic FSGS between 2005 and 2015 and details were recorded about the transplant, clinical outcomes, treatments, and other risk factors. RESULTS: Among 11,742 kidney transplant recipients screened for FSGS, 176 had a diagnosis of idiopathic FSGS and were included. FSGS recurred in 57 patients (32%; 95% confidence interval [95% CI], 25% to 39%) and 39% of them lost their graft over a median of 5 (interquartile range, 3.0-8.1) years. Multivariable Cox regression revealed a higher risk for recurrence with older age at native kidney disease onset (hazard ratio [HR], 1.37 per decade; 95% CI, 1.09 to 1.56). Other predictors were white race (HR, 2.14; 95% CI, 1.08 to 4.22), body mass index at transplant (HR, 0.89 per kg/m2; 95% CI, 0.83 to 0.95), and native kidney nephrectomies (HR, 2.76; 95% CI, 1.16 to 6.57). Plasmapheresis and rituximab were the most frequent treatments (81%). Partial or complete remission occurred in 57% of patients and was associated with better graft survival. CONCLUSIONS: Idiopathic FSGS recurs post-transplant in one third of cases and is associated with a five-fold higher risk of graft loss. Response to treatment is associated with significantly better outcomes but is achieved in only half of the cases.
Asunto(s)
Glomeruloesclerosis Focal y Segmentaria/cirugía , Supervivencia de Injerto , Trasplante de Riñón/efectos adversos , Adulto , Brasil , Europa (Continente) , Femenino , Glomeruloesclerosis Focal y Segmentaria/diagnóstico , Glomeruloesclerosis Focal y Segmentaria/fisiopatología , Supervivencia de Injerto/efectos de los fármacos , Humanos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Plasmaféresis , Recurrencia , Retratamiento , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Rituximab/uso terapéutico , Factores de Tiempo , Resultado del Tratamiento , Estados UnidosRESUMEN
Histoplasmosis is a fungus infection that mainly affects immunosuppressed patients. The authors present a case of a kidney transplant recipient who developed sepsis-like histoplasmosis, na atypical but severe manifestation of the disease. The fungus was found in blood and in a skin biopsy, and the treatment with liposomal amphotericin resulted in hepatotoxicity.
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Histoplasmosis , Trasplante de Riñón , Complicaciones Posoperatorias , Sepsis , Resultado Fatal , Femenino , Histoplasmosis/diagnóstico , Histoplasmosis/tratamiento farmacológico , Humanos , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/tratamiento farmacológico , Sepsis/diagnóstico , Sepsis/tratamiento farmacológicoRESUMEN
There are scarce data about clinical presentation and outcomes of posttransplant membranous nephropathy (MN), and few reports include a large number of patients. This was a retrospective cohort including adult patients with posttransplant MN transplanted between 1983 and 2015 in a single center (n=41). Only patients with histological diagnosis of MN in kidney grafts were included. Clinical and laboratory presentation, histological findings, treatment, and outcomes were detailed. Patients were predominantly male (58.5%), with a mean age of 49.4 ± 13.2 years; 15 were considered as recurrent primary MN; 3 were class V lupus nephritis; 14 were considered as de novo cases, 7 secondary and 7 primary MN; and 9 cases were considered primary but it was not possible to distinguish between de novo MN and recurrence. Main clinical presentations were proteinuria (75.6%) and graft dysfunction (34.1%). Most patients with primary recurrent and de novo primary MN were submitted to changes in maintenance immunosuppressive regimen, but no standard strategy was identified; 31 patients presented partial or complete remission, and glomerulopathy appeared not to impact graft and patient survival.
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An insoluble white substance was prepared from extracts of eggshells of Aedes aegypti, the yellow fever mosquito and dengue vector. Its infrared and proton NMR spectra were similar to that of standard commercial chitin. This putative chitin-like material, also obtained from ovaries, newly laid and dark eggs, was hydrolyzed in acid and a major product was identified by HPLC to be glucosamine. The eggshell acid hydrolysate was also analyzed by ESI-MS and an ion identical to a glucosamine monoprotonated species was detected. The presence of chitin was also analyzed during different developmental stages of the ovary using a fluorescent microscopy technique and probes specific for chitin. The results showed that a chitin-like material accumulates in oocytes during oogenesis. Streptomyces griseus chitinase pre-treatment of oocytes greatly reduced the chitin-derived fluorescence. Chitinase activity was detected in newborn larvae and eggs prior to hatching. Feeding experiments indicated that the chitin synthesis inhibitor lufenuron inhibited chitin synthesis, either when mosquitoes were allowed to feed directly on lufenuron-treated chickens or when an artificial feeding system was used. Lufenuron inhibited egg hatch, larval development and reduced mosquito viability. These data demonstrate for the first time that (1) a chitin-like material is present in A. aegypti eggs, ovaries and eggshells; (2) a chitin synthesis inhibitor can be used to inhibit mosquito oogenesis; and (3) chitin synthesis inhibitors have potential for controlling mosquito populations.
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Aedes/metabolismo , Quitina/biosíntesis , Aedes/efectos de los fármacos , Aedes/enzimología , Animales , Benzamidas/farmacología , Quitina/antagonistas & inhibidores , Quitinasas/metabolismo , Femenino , Insecticidas/farmacología , Larva/efectos de los fármacos , Ovario/metabolismo , Óvulo/efectos de los fármacos , Óvulo/enzimología , Óvulo/metabolismo , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
Mycobacterium tuberculosis infection in renal transplant recipients is associated with significant morbidity and mortality. Genitourinary tuberculosis is a less frequent presentation and a high level of suspicion is needed to avoid treatment delay. Management is challenging due to the interaction of calcineurin inhibitors with antituberculous medications and the known side effects of these drugs, with higher prevalence in this population. The authors present a case of a renal transplant recipient with urinary and constitutional symptoms whom is diagnosed with tuberculosis after a prostatic biopsy in an already disseminated stage and develops hepatotoxicity to antituberculous therapy.
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Trasplante de Riñón , Complicaciones Posoperatorias/diagnóstico , Tuberculosis Urogenital/diagnóstico , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: De novo use of mammalian target of rapamycin inhibitors after kidney transplantation is associated with a concentration-dependent incidence of wound healing adverse events (WHAE). The objective of this analysis was to compare the incidence of WHAE in patients receiving everolimus (EVR) or mycophenolate sodium (MPS). METHODS: This was a predefined subanalysis of a single-center prospective randomized study in which 288 kidney transplant recipients receiving tacrolimus and prednisone were randomized for 3 different regimens: rabbit antithymocyte globulin (r-ATG)/EVR (N = 85); basiliximab (BAS)/EVR (N = 102); BAS/MPS (N = 101). Clinical WHAE were prospectively collected using a prespecified case report form in all study visits. Abdominal ultrasound was performed at 30 days posttransplant to capture subclinical abnormalities. Surgeons were blinded to randomized treatment and no specific surgical procedures were implemented. RESULTS: A higher proportion of patients in BAS/EVR showed at least 1 clinical WHAE (22.3% vs 35.3% vs 22.0%, P = 0.03) and total clinical and subclinical WHAE (35% vs 42% vs 26%, P = 0.014) compared with BAS/MPS, respectively. A higher proportion of patients in r-ATG/EVR showed subclinical WHAE (13% vs 7% vs 4%, P = 0.025) compared with BAS/MPS, respectively. Patients receiving EVR showed a higher risk of developing clinical or subclinical WHAE (r-ATG/EVR vs BAS/MPS hazard ratio 1.30; BAS/EVR vs BAS/MPS hazard ratio 1.73, P = 0.028). CONCLUSIONS: In this cohort of de novo kidney transplant recipients receiving tacrolimus and prednisone, the use of EVR was associated with higher incidence of combined clinical and subclinical WHAE compared with MPS.
Asunto(s)
Everolimus/efectos adversos , Inmunosupresores/efectos adversos , Trasplante de Riñón/efectos adversos , Ácido Micofenólico/efectos adversos , Cicatrización de Heridas/efectos de los fármacos , Adulto , Anticuerpos Monoclonales/efectos adversos , Suero Antilinfocítico/efectos adversos , Basiliximab , Brasil , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prednisona/efectos adversos , Estudios Prospectivos , Proteínas Recombinantes de Fusión/efectos adversos , Factores de Riesgo , Tacrolimus/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , UltrasonografíaRESUMEN
Cytomegalovirus (CMV) infection in kidney transplantation has changed its clinical spectrum, mostly due to the current and more effective immunosuppression. In the absence of preventive strategies it is associated with significant morbi-mortality. OBJECTIVE: This study evaluated the incidence of CMV events and its effect on outcomes of kidney transplantation in recipients without pharmacological prophylaxis or targeted preemptive treatment. RESULTS: The study cohort comprised 802 recipients of kidney transplants between 04/30/2014 and 04/30/2015. The majority received induction with anti-thymocyte globulin (81.5%), tacrolimus and prednisone in combination with either mycophenolate (46.3%) or azathioprine (53.7%). The overall incidence of CMV events was 42% (58.6% infection and 41.4% disease). Patients with CMV showed higher incidence of first treated acute rejection (19 vs. 11%, p = 0,001) compared with those without CMV but no differences in graft loss, death or loss to follow-up. The incidence of delayed graft function was higher (56% vs. 37%, p = 0.000) and the eGFR at 1 (41 ± 21 vs. 54 ± 28 ml/min, p = 0.000) and 12 months (50 ± 19 vs. 61 ± 29 ml/min, p = 0.000) were lower in patients with CMV. Recipients age (OR = 1.03), negative CMV serology (OR = 5.21) and use of mycophenolate (OR = 1.67) were associated with increased risk of CMV. Changes in immunosuppression was more often in patients with CMV (63% vs. 31%, p = 0.000). CONCLUSION: the incidence of CMV events was high and associated with higher incidence of acute rejection and changes in immunosuppression. Besides traditional risk factors, renal function at 1 month was independently associated with CMV infection.
Asunto(s)
Infecciones por Citomegalovirus/epidemiología , Trasplante de Riñón , Complicaciones Posoperatorias/epidemiología , Adulto , Costo de Enfermedad , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: Modern immunosuppressive regimens, although associated with improved 1-year graft survival, are associated with adverse effects, including opportunistic infections, diabetes mellitus after transplantation, cardiovascular complications, and de novo malignancies. OBJECTIVES: To determine the short-term (12 months) cost-effectiveness of everolimus (EVR) versus mycophenolate sodium (MPS) in kidney transplant recipients receiving induction therapy, tacrolimus, prednisone, and no prophylaxis for cytomegalovirus infection. METHODS: A Markov state transition model was designed. Data from a single-center prospective trial were used along with data from the center's medical bills database. The target population comprised adults with low immunological risk submitted to first ABO-compatible transplantation with kidneys recovered from living or deceased donors. The time horizon was 12 months. The interventions included tacrolimus and prednisone plus a single 3-mg/kg dose of rabbit antithymocyte globulin (ATG) and EVR or basiliximab (BAS) and EVR or BAS and MPS. The clinical outcomes considered for this analysis were cytomegalovirus infection/disease, acute rejection, graft dysfunction, surgical complications, graft loss, and life-years gained. RESULTS: ATG/EVR was cost-saving compared with BAS/MPS on all evaluated outcomes; BAS/EVR outperformed BAS/MPS on most of the evaluated outcomes. Results were confirmed by sensitivity analysis. CONCLUSIONS: Compared with MPS, EVR is an alternative immunosuppressive agent that is able to provide resource-saving to the health care provider with effectiveness gains for the patient.