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1.
Front Transplant ; 2: 1279940, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38993903

RESUMEN

Introduction: The combination of tacrolimus/mTORi compared to tacrolimus/mycophenolate (MMF) was shown to be safe in the TRANSFORM trial. For donors with a high KDPI (Kidney Donor Profile Index), however, there are no data to support the effectiveness of this regimen. The main objective of this study was to explore the influence of the KDPI on 12-month renal function (eGFR) in patients receiving mTORi or MMF. Methods: Multicenter cohort study of four Brazilian services that use the tacrolimus with mTORi as a protocol. Data from 2008 to 2018 of the tacrolimus/mycophenolate (MMF) and tacrolimus/mTORi (mTORi) regimens in renal transplant recipients over 18 years old were collected. For better homogeneity, the propensity score was used. Afterward, the method used for group selection ("match") was the K-nearest neighbor (KNN) method. New analyses were performed on this new balanced sample, and two different subsamples were constituted based on the median KDPI. Results: The global analysis (n = 870) showed that the major determinant of worse kidney function was high KDPI. Afterward, the three strata were analyzed. In the first stratum (KDPI up to 50), 242 patients were evaluated, with 121 in each group. The eGFR was 64 ml/min/1.73 m2 in the mTORi group compared to 63 in the MMF group, p = 0.4, and when imputed eGFR was evaluated, 61 in the mTORi and 53 in the MMF, p = 0.065. In the second stratum (KDPI from 50 to 85), 282 patients were evaluated, with 141 in each group. eGFR was 46 ml/min/1.73 m2 in mTORi compared to 48 in MMF, p = 0.4, and when imputed eGFR was evaluated, 40 mTORi and 41 MMF, p = 0.8. In the last stratum (KDPI higher than 85) with n = 126 and 63 cases per group, eGFR was 36 ml/min/1.73 m2 in mTORi compared to 39 in MMF, p = 0.2, and when imputed eGFR was evaluated, 30 mTORi and 34 MMF, p = 0.2. Discussion: The regimen using mTOR inhibitor is an effective and safe regimen when compared to the standard regimen. In addition, the scheme seems to offer additional protection against infections and may be an important ally in cases of high risk for these pathologies.

2.
Int J Artif Organs ; 45(8): 680-684, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35751365

RESUMEN

Rapid tests (RT) have been widely used for screening of hepatitis C virus (HCV) in general population, but its performance in hemodialysis (HD) patients and mainly in kidney-transplant recipients (RTx) is less known. The aim of this study was to evaluate the accuracy of RT for detection of anti-HCV in HD and RTx patients. Patients were prospectively included subdivided in four groups according to the positivity for anti-HCV detected by conventional serology: (1) HD patients anti-HCV +, (2) HD patients anti-HCV -, (3) RTx patients anti-HCV +, and (4) RTx patients anti-HCV -. All patients were retested for HCV using the commercial kit Alere HCV® Bioeasy Rapid Test (Bioeasy Diagnóstica LTDA-Minas Gerais, Brazil) in capillary whole blood samples. During the period of study were included 46 HD patients anti-HCV+, 62 HD patients anti-HCV -, 53 RTx patients anti-HCV + and 56 RTx patients anti-HCV -. In patients on HD, the RT showed sensitivity (S), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), and accuracy of 100%. In RTx patients, S of 96%, SP of 100%, PPV of 100% and NPV of 97% were found (accuracy of 98%). In conclusion, in patients on HD there was 100% agreement between RT and the conventional immunoassay. In the RTx group, although the agreement was not 100%, the RT performed very well when compared to conventional serology. This study demonstrates that the RT can be an alternative to conventional serology in HCV screening of patients on HD and RTx.


Asunto(s)
Hepatitis C , Trasplante de Riñón , Hepacivirus , Hepatitis C/diagnóstico , Anticuerpos contra la Hepatitis C , Humanos , Trasplante de Riñón/efectos adversos , Diálisis Renal , Receptores de Trasplantes
4.
Arq Gastroenterol ; 59(1): 65-70, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35442339

RESUMEN

BACKGROUND: Kidney transplant is the treatment of choice for patients with end-stage renal disease and is associated with lower mortality when compared to dialysis methods. Brazil is the country with the second largest number of kidney transplants in the world and among these patients it has been observed that liver abnormalities are common. The frequency of liver abnormalities ranges from 20-50% post-transplantation, and have an important impact on the survival and quality of life of these patients. There are scarce data about the frequency, causes and characteristics of these alterations. OBJECTIVE: To determine the prevalence of the different causes of hepatic abnormalities in kidney transplant recipients, to associate the characteristics of these abnormalities with demographic, epidemiological and clinical variables, to compare the characteristics of hepatic alterations between different etiologies, and to evaluate possible changes in diagnosis over two different periods of time. METHODS: Descriptive, cross-sectional observational, epidemiological study was conducted at the outpatient "Hepato-Rim"clinic of Hospital São Paulo (EPM/UNIFESP), a center providing specialized care for patients with hepatic abnormalities and underlying kidney diseases. RESULTS: Five-hundred eighty-one transplant patients were evaluated. The most prevalent etiologies of liver abnormalities were hepatitis C and B, iron overload, nonalcoholic fatty liver disease (NAFLD), and drug-induced liver injury (DILI). The most common cause - hepatitis C - was analyzed in greater detail. Compared to the other causes, this infection was more frequent in older patients, female patients, and patients with a longer time since transplantation and hemodialysis. Analysis of the two periods showed that patients of period 1 (P1 - 1993 to 2005) were older and were more frequently referred because of positive serology; referral due to aminotransferases abnormalities predominated during period 2 (P2 - 2006 to 2018). The predominant diagnoses were hepatitis C and B during P1 and NAFLD and DILI during P2. CONCLUSION: Assessment of the main hepatic alterations in kidney transplant recipients is important because it permits better management of these patients in terms of diagnostic investigation and treatment and contributes to the prevention of complications in this special population.


Asunto(s)
Hepatitis C , Trasplante de Riñón , Enfermedad del Hígado Graso no Alcohólico , Anciano , Brasil/epidemiología , Estudios Transversales , Femenino , Hepacivirus , Hepatitis C/complicaciones , Hepatitis C/epidemiología , Humanos , Trasplante de Riñón/efectos adversos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Calidad de Vida
5.
Acta Cir Bras ; 37(2): e370202, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35475809

RESUMEN

PURPOSE: Simultaneous pancreas-kidney transplantation (SPKT) brings several benefits for insulin-dependent type-1 diabetic patients associated with end-stage renal disease (ESRD). However, data on psychological outcomes for the waiting list and the transplanted patients are still lacking. METHODS: Using the psychological Beck inventories of anxiety (BAI) and depression (BDI), 39 patients on the waiting list were compared to 88 post-transplanted patients who had undergone SPKT. RESULTS: Significant differences were found regarding depression (p = 0.003) but not anxiety (p = 0.161), being the pretransplant patients more vulnerable to psychological disorders. Remarkable differences were observed relative to the feeling of punishment (p < 0.001) and suicidal thoughts (p = 0.008) between the groups. It was observed that patients who waited a longer period for the transplant showed more post-transplant anxiety symptoms due to the long treatment burden (p = 0.002). CONCLUSIONS: These results demonstrated the positive impact of SPKT on psychological aspects related to depression when comparing the groups. The high number of stressors in the pretransplant stage impacts more severely the psychosocial condition of the patient.


Asunto(s)
Fallo Renal Crónico , Trasplante de Riñón , Trasplante de Páncreas , Estudios Transversales , Femenino , Humanos , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/métodos , Masculino , Páncreas , Trasplante de Páncreas/efectos adversos , Trasplante de Páncreas/métodos
6.
Int J Paediatr Dent ; 32(6): 894-902, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35316550

RESUMEN

BACKGROUND: Children and adolescents undergoing kidney transplantation may present oral conditions after the procedure, but a few studies have recently described them. AIM: To describe the oral conditions of post-renal transplant children and adolescents. DESIGN: Two calibrated dentists examined all the participants by assessing caries experience, enamel defects, periodontal condition and soft tissue lesions. RESULTS: A total of 120 participants were included in the study, in which 63 (52.5%) were male and 57 (47.5%) were female, with a mean age of 12.78 ± 3.9 years. Among the participants, 104 (86.7%) showed at least one oral change directly related to kidney disease. The most frequent oral findings were enamel defect (49/120; 40.8%) and drug-induced gingival overgrowth (DIGO) (20/120; 16.7%). Gingival bleeding was observed on probing in 115 (95.8%) participants, whereas 69 (57.5%) presented dental calculus and 51 (42.5%) had caries experience. CONCLUSION: Gingival bleeding, enamel defects and DIGO were the most frequent oral findings in kidney transplant children and adolescents. The use of amlodipine and anticonvulsants was associated with DIGO, and there was a positive correlation between oral ulcers and use of everolimus.


Asunto(s)
Caries Dental , Sobrecrecimiento Gingival , Trasplante de Riñón , Enfermedades Dentales , Adolescente , Amlodipino/efectos adversos , Anticonvulsivantes/efectos adversos , Niño , Everolimus/efectos adversos , Femenino , Sobrecrecimiento Gingival/inducido químicamente , Sobrecrecimiento Gingival/patología , Humanos , Trasplante de Riñón/efectos adversos , Masculino , Salud Bucal
7.
Arq. gastroenterol ; Arq. gastroenterol;59(1): 65-70, Jan.-Mar. 2022. tab, graf
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1374440

RESUMEN

ABSTRACT Background Kidney transplant is the treatment of choice for patients with end-stage renal disease and is associated with lower mortality when compared to dialysis methods. Brazil is the country with the second largest number of kidney transplants in the world and among these patients it has been observed that liver abnormalities are common. The frequency of liver abnormalities ranges from 20-50% post-transplantation, and have an important impact on the survival and quality of life of these patients. There are scarce data about the frequency, causes and characteristics of these alterations. Objective To determine the prevalence of the different causes of hepatic abnormalities in kidney transplant recipients, to associate the characteristics of these abnormalities with demographic, epidemiological and clinical variables, to compare the characteristics of hepatic alterations between different etiologies, and to evaluate possible changes in diagnosis over two different periods of time. Methods Descriptive, cross-sectional observational, epidemiological study was conducted at the outpatient "Hepato-Rim"clinic of Hospital São Paulo (EPM/UNIFESP), a center providing specialized care for patients with hepatic abnormalities and underlying kidney diseases. Results Five-hundred eighty-one transplant patients were evaluated. The most prevalent etiologies of liver abnormalities were hepatitis C and B, iron overload, nonalcoholic fatty liver disease (NAFLD), and drug-induced liver injury (DILI). The most common cause — hepatitis C — was analyzed in greater detail. Compared to the other causes, this infection was more frequent in older patients, female patients, and patients with a longer time since transplantation and hemodialysis. Analysis of the two periods showed that patients of period 1 (P1 — 1993 to 2005) were older and were more frequently referred because of positive serology; referral due to aminotransferases abnormalities predominated during period 2 (P2 — 2006 to 2018). The predominant diagnoses were hepatitis C and B during P1 and NAFLD and DILI during P2. Conclusion Assessment of the main hepatic alterations in kidney transplant recipients is important because it permits better management of these patients in terms of diagnostic investigation and treatment and contributes to the prevention of complications in this special population.


RESUMO Contexto O transplante renal é o tratamento de escolha para pacientes com doença renal terminal e está associado a menor mortalidade quando comparado aos métodos dialíticos. O Brasil é o país com o segundo maior número de transplantes renais do mundo e, entre esses pacientes, observa-se que as alterações hepáticas são comuns. A frequência das alterações hepáticas varia de 20 a 50% pós-transplante e tem importante impacto na sobrevida e qualidade de vida desses pacientes. Existem poucos dados sobre a frequência, causas e características dessas alterações. Objetivo Determinar a prevalência das diferentes causas de anormalidades hepáticas em receptores de transplante renal, associar as características dessas anormalidades a variáveis demográficas, epidemiológicas e clínicas, comparar as características das alterações hepáticas entre diferentes etiologias e avaliar possíveis alterações no diagnóstico em dois períodos diferentes de tempo. Métodos Estudo epidemiológico descritivo, transversal, observacional, realizado no ambulatório "Hepato-Rim" do Hospital São Paulo (EPM/UNIFESP), centro de atendimento especializado a pacientes com anormalidades hepáticas e doenças renais de base. Resultados Quinhentos e oitenta e um pacientes transplantados foram avaliados. As etiologias mais prevalentes de anormalidades hepáticas foram hepatite C e B, sobrecarga de ferro, doença hepática gordurosa não alcoólica e lesão hepática induzida por drogas. A causa mais comum — hepatite C — foi analisada em maiores detalhes. Em comparação com as outras causas, essa infecção foi a mais frequente em pacientes mais velhos, pacientes do sexo feminino e pacientes com mais tempo de transplante e hemodiálise. A análise dos dois períodos mostrou que os pacientes do período 1 (P1 — 1993 a 2005) eram mais velhos e encaminhados com maior frequência devido à sorologia positiva; encaminhamento devido a anormalidades de aminotransferases predominou durante o período 2 (P2 — 2006 a 2018). Os diagnósticos predominantes foram hepatite C e B durante P1 e doença hepática gordurosa não alcoólica e lesão hepática induzida por drogas durante P2. Conclusão A avaliação das principais alterações hepáticas em receptores de transplante renal é importante, pois permite melhor manejo desses pacientes na investigação diagnóstica e no tratamento e contribui para a prevenção de complicações nesta população especial.

8.
Transpl Int ; 35: 10205, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35185380

RESUMEN

Data from the general population suggest that fatality rates declined during the course of the pandemic. This analysis, using data extracted from the Brazilian Kidney Transplant COVID-19 Registry, seeks to determine fatality rates over time since the index case on March 3rd, 2020. Data from hospitalized patients with RT-PCR positive SARS-CoV-2 infection from March to August 2020 (35 sites, 878 patients) were compared using trend tests according to quartiles (Q1: <72 days; Q2: 72-104 days; Q3: 105-140 days; Q4: >140 days after the index case). The 28-day fatality decreased from 29.5% (Q1) to 18.8% (Q4) (pfor-trend = 0.004). In multivariable analysis, patients diagnosed in Q4 showed a 35% reduced risk of death. The trend of reducing fatality was associated with a lower number of comorbidities (20.7-10.6%, p for-trend = 0.002), younger age (55-53 years, pfor-trend = 0.062), and better baseline renal function (43.6-47.7 ml/min/1.73 m2, pfor-trend = 0.060), and were confirmed by multivariable analysis. The proportion of patients presenting dyspnea (pfor-trend = 0.001) and hypoxemia (pfor-trend < 0.001) at diagnosis, and requiring intensive care was also found reduced (pfor-trend = 0.038). Despite possible confounding variables and time-dependent sampling differences, we conclude that COVID-19-associated fatality decreased over time. Differences in demographics, clinical presentation, and treatment options might be involved.


Asunto(s)
COVID-19 , Trasplante de Riñón , Estudios de Cohortes , Humanos , Trasplante de Riñón/efectos adversos , Sistema de Registros , SARS-CoV-2 , Receptores de Trasplantes
9.
J Nephrol ; 35(1): 131-141, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34677805

RESUMEN

BACKGROUND AND OBJECTIVES: Patients undergoing kidney replacement therapies (KRTs) have a poor prognosis after Covid-19 infection. Few studies have compared the outcomes of such patients in the different KRT modalities. This study aimed to analyze the 30-day Covid-19-associated case-fatality rate of dialysis and kidney transplant patients. METHODS: Retrospective cohort study analyzing data from patients with confirmed Covid-19 between Mar/20 and Jan/21 included in two multicenter studies, the Brazilian Covid-19 Dialysis Study (Dialysis group, n = 703) and the Covid-19-KT Brazilian Study (Transplant group, n = 1907). To assess the risk factors for death, adjusted Cox hazards models were used. A sensitivity analysis was performed using a propensity score analysis to match the groups (n = 587 patients in each group). RESULTS: A higher percentage of transplant patients required hospitalization (68 vs. 51%, p < 0.001), intensive care (37 vs. 30%, p = 0.023), and invasive mechanical ventilation (28 vs. 22%, p = 0.035). Multivariate analysis of the before-matching sample showed that subjects in the transplant group were at a lower death risk at baseline (HR 0.380.560.85). However, they showed higher risk over time (HR 1.031.061.09). Kaplan-Meier analysis after propensity score matching confirmed the inferior 30-day cumulative survival in the transplant recipients (83 vs. 78%, p = 0.0014). CONCLUSION: Both transplant and dialysis patients have high 30-day case-fatality rates after a Covid-19 diagnosis. Despite lower death risk at baseline, transplant patients have an increased death risk of 6% per day than dialysis patients.


Asunto(s)
Prueba de COVID-19 , COVID-19 , Estudios de Cohortes , Humanos , Puntaje de Propensión , Diálisis Renal/efectos adversos , Estudios Retrospectivos , SARS-CoV-2
10.
Acta cir. bras ; 37(2): e370202, 2022. tab
Artículo en Inglés | LILACS, VETINDEX | ID: biblio-1374070

RESUMEN

Purpose: Simultaneous pancreas-kidney transplantation (SPKT) brings several benefits for insulin-dependent type-1 diabetic patients associated with end-stage renal disease (ESRD). However, data on psychological outcomes for the waiting list and the transplanted patients are still lacking. Methods: Using the psychological Beck inventories of anxiety (BAI) and depression (BDI), 39 patients on the waiting list were compared to 88 post-transplanted patients who had undergone SPKT. Results: Significant differences were found regarding depression (p = 0.003) but not anxiety (p = 0.161), being the pretransplant patients more vulnerable to psychological disorders. Remarkable differences were observed relative to the feeling of punishment (p < 0.001) and suicidal thoughts (p = 0.008) between the groups. It was observed that patients who waited a longer period for the transplant showed more post-transplant anxiety symptoms due to the long treatment burden (p = 0.002). Conclusions: These results demonstrated the positive impact of SPKT on psychological aspects related to depression when comparing the groups. The high number of stressors in the pretransplant stage impacts more severely the psychosocial condition of the patient.


Asunto(s)
Humanos , Ansiedad/diagnóstico , Cuidados Posoperatorios/psicología , Cuidados Preoperatorios/psicología , Trasplante de Riñón/psicología , Trasplante de Páncreas/psicología , Depresión/diagnóstico , Calidad de Vida , Estudios Transversales
11.
Artículo en Inglés | MEDLINE | ID: mdl-34925477

RESUMEN

Coronavirus disease 2019 (COVID-19) is a rapid-spread infectious disease caused by the SARS-CoV-2 virus, which can culminate in the renin-angiotensin-aldosterone (RAAS) and kallikrein-kinin (KKS) systems imbalance, and in serious consequences for infected patients. This scoping review of published research exploring the RAAS and KKS was undertaken in order to trace the history of the discovery of both systems and their multiple interactions, discuss some aspects of the viral-cell interaction, including inflammation and the system imbalance triggered by SARS-CoV-2 infection, and their consequent disorders. Furthermore, we correlate the effects of continued use of the RAAS blockers in chronic diseases therapies with the virulence and physiopathology of COVID-19. We also approach the RAAS and KKS-related proposed potential therapies for treatment of COVID-19. In this way, we reinforce the importance of exploring both systems and the application of their components or their blockers in the treatment of coronavirus disease.

12.
Transpl Int ; 34(6): 1093-1104, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33742470

RESUMEN

This retrospective multicenter (n = 18) cohort study evaluated the incidence, risk factors, and the impact of delayed graft function (DGF) on 1-year kidney transplant (KT) outcomes. Of 3992 deceased donor KT performed in 2014-2015, the incidence of DGF was 54%, ranging from 29.9% to 87.7% among centers. Risk factors (lower-bound-95%CI OR upper-bound-95%CI ) were male gender (1.066 1.2491.463 ), diabetic kidney disease (1.053 1.2961.595 ), time on dialysis (1.005 1.0071.009 ), retransplantation (1.035 1.3971.885 ), preformed anti-HLA antibodies (1.011 1.3831.892 ), HLA mismatches (1.006 1.0661.130 ), donor age (1.011 1.0171.023 ), donor final serum creatinine (sCr) (1.239 1.3171.399 ), cold ischemia time (CIT) (1.031 1.0431.056 ), machine perfusion (0.401 0.5420.733 ), and induction therapy with rabbit antithymocyte globulin (rATG) (0.658 0.8000.973 ). Duration of DGF > 4 days was associated with inferior renal function and DGF > 14 days with the higher incidences of acute rejection, graft loss, and death. In conclusion, the incidence and duration of DGF were high and associated with inferior graft outcomes. While late referral and poor donor maintenance account for the high overall incidence of DGF, variability in donor and recipient selection, organ preservation method, and type of induction agent may account for the wide variation observed among transplant centers.


Asunto(s)
Trasplante de Riñón , Brasil/epidemiología , Estudios de Cohortes , Funcionamiento Retardado del Injerto/epidemiología , Funcionamiento Retardado del Injerto/etiología , Rechazo de Injerto/epidemiología , Rechazo de Injerto/etiología , Supervivencia de Injerto , Humanos , Incidencia , Trasplante de Riñón/efectos adversos , Masculino , Estudios Retrospectivos , Factores de Riesgo , Donantes de Tejidos
14.
J. venom. anim. toxins incl. trop. dis ; J. venom. anim. toxins incl. trop. dis;27: e20200181, 2021. graf
Artículo en Inglés | LILACS, VETINDEX | ID: biblio-1351022

RESUMEN

Coronavirus disease 2019 (COVID-19) is a rapid-spread infectious disease caused by the SARS-CoV-2 virus, which can culminate in the renin-angiotensin-aldosterone (RAAS) and kallikrein-kinin (KKS) systems imbalance, and in serious consequences for infected patients. This scoping review of published research exploring the RAAS and KKS was undertaken in order to trace the history of the discovery of both systems and their multiple interactions, discuss some aspects of the viral-cell interaction, including inflammation and the system imbalance triggered by SARS-CoV-2 infection, and their consequent disorders. Furthermore, we correlate the effects of continued use of the RAAS blockers in chronic diseases therapies with the virulence and physiopathology of COVID-19. We also approach the RAAS and KKS-related proposed potential therapies for treatment of COVID-19. In this way, we reinforce the importance of exploring both systems and the application of their components or their blockers in the treatment of coronavirus disease.(AU)


Asunto(s)
Virulencia , Angiotensinas , Calicreínas , Coronavirus , Aldosterona , SARS-CoV-2 , Inflamación
15.
J. venom. anim. toxins incl. trop. dis ; J. venom. anim. toxins incl. trop. dis;272021.
Artículo en Inglés | LILACS-Express | LILACS, VETINDEX | ID: biblio-1484778

RESUMEN

Abstract Coronavirus disease 2019 (COVID-19) is a rapid-spread infectious disease caused by the SARS-CoV-2 virus, which can culminate in the renin-angiotensin-aldosterone (RAAS) and kallikrein-kinin (KKS) systems imbalance, and in serious consequences for infected patients. This scoping review of published research exploring the RAAS and KKS was undertaken in order to trace the history of the discovery of both systems and their multiple interactions, discuss some aspects of the viral-cell interaction, including inflammation and the system imbalance triggered by SARS-CoV-2 infection, and their consequent disorders. Furthermore, we correlate the effects of continued use of the RAAS blockers in chronic diseases therapies with the virulence and physiopathology of COVID-19. We also approach the RAAS and KKS-related proposed potential therapies for treatment of COVID-19. In this way, we reinforce the importance of exploring both systems and the application of their components or their blockers in the treatment of coronavirus disease.

16.
Epigenomics ; 12(22): 2019-2034, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33275448

RESUMEN

Aim: To analyze the expression of urinary exosome-derived miRNAs (exo-miRs) in kidney recipients on tacrolimus-based therapy. Patients & methods: Clinical and drug monitoring data were recorded from 23 kidney recipients. Expression of 93 exo-miRs was measured by quantitative PCR array and mRNA targets were explored. Results: 16 exo-miRs were differentially expressed, including marked upregulation of miR-155-5p, and downregulation of miR-223-3p and miR-1228-3p. Expression of miR-155-5p and miR-223-3p correlated with tacrolimus dose (p < 0.05), miR-223-3p with serum creatinine (p < 0.05), and miR-223-3p and miR-1228-3p with blood leukocytes (p < 0.05). 12 miRNAs have predicted targets involved in cell proliferation, apoptosis, stress response, PIK3/AKT/mTOR and TGF-ß signaling pathways. Conclusion: Differentially expressed urinary exo-miRs may be useful markers to monitor tacrolimus therapy and graft function in kidney transplantation.


Asunto(s)
Exosomas/genética , Inmunosupresores/uso terapéutico , Trasplante de Riñón , MicroARNs/orina , Tacrolimus/uso terapéutico , Adulto , Citocromo P-450 CYP3A/genética , Femenino , Regulación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Resultado del Tratamiento
17.
Ann Transl Med ; 8(17): 1051, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33145270

RESUMEN

BACKGROUND: Genetic and epigenetics factors have been implicated in drug response, graft function and rejection in solid organ transplantation. Differential expression of genes involved in calcineurin and mTOR signaling pathway and regulatory miRNAs was analyzed in the peripheral blood of kidney recipient cohort (n=36) under tacrolimus-based therapy. METHODS: PPP3CA, PPP3CB, MTOR, FKBP1A, FKBP1B and FKBP5 mRNA expression and polymorphisms in PPP3CA and MTOR were analyzed by qPCR. Expression of miRNAs targeting PPP3CA (miR-30a, miR-145), PPP3CB (miR-10b), MTOR (miR-99a, miR-100), and FKBP1A (miR-103a) was measured by qPCR array. RESULTS: PPP3CA and MTOR mRNA levels were reduced in the first three months of treatment compared to pre-transplant (P<0.05). PPP3CB, FKBP1A, FKBP1B, and FKBP5 expression was not changed. In the 3rd month of treatment, the expression of miR-99a, which targets MTOR, increased compared to pre-transplant (P<0.05). PPP3CA c.249G>A (GG genotype) and MTOR c.2997C>T (TT genotype) were associated with reduced expression of PPP3CA mRNA and MTOR, respectively. FKBP1B mRNA levels were higher in patients with acute rejection (P=0.026). CONCLUSIONS: The expression of PPP3CA, MTOR and miR-99a in the peripheral blood of renal recipients is influenced by tacrolimus-based therapy and by PPP3CA and MTOR variants. These molecules can be potential biomarkers for pharmacotherapy monitoring.

19.
Transplant Proc ; 52(1): 89-96, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32000943

RESUMEN

BACKGROUND: After renal transplantation (RTx) hepatitis C virus (HCV) is associated with higher morbidity and mortality resulting in lower patient and graft survival. Few studies have investigated the evolution of renal transplant patients with cirrhosis owing to HCV. The objectives were to evaluate the post-transplant evolution of cirrhotic patients and to compare them with noncirrhotic patients considering the outcomes, including hepatic decompensation, graft loss, and death. METHODS: The retrospective-cohort study analyzed the data of patients undergoing RTx between 1993 and 2014, positive anti-HCV, HCV-RNA before RTx, and availability of data for assessment of cirrhosis. Demographic, clinical, and laboratory variables were compared between the groups according to the outcomes. The same were made between cirrhotic patients with and without portal hypertension (PH). Survival curves were constructed by the Kaplan-Meier test and compared by the log-rank test. Variables associated with the outcomes were analyzed using Cox regression. RESULTS: This study included noncirrhotic (n = 201) and cirrhotic patients (n = 23). In cirrhotic patients, they were significantly older (49 vs 41.6 years) and mostly male (87% vs 65%), with a greater number of previous RTx (48% vs 18%), less frequent use of azathioprine (26% vs 54%), cyclosporine (13% vs 46.5%), more frequent use of tacrolimus (87% vs 55%), lower count of platelets × 1000 cells/mm3(110 vs 187), and higher pre-RTx international normalized ratio (1.20 vs 1.1).The Kaplan-Meier survival differed in cirrhotic vs noncirrhotic patients only in hepatic decompensation. Cox regression analysis identified pretransplant cirrhosis (hazard ratio 6.64, 95% confidence interval, 2.59-17.06) and tacrolimus (hazard ratio 3.17,95% confidence interval, 1.05-9.58) as variables independently associated with decompensation. CONCLUSIONS: Patients with HCV and cirrhosis exhibit higher morbidity when submitted to RTx than noncirrhotic patients, with a higher risk of hepatic decompensation. However, no difference was observed in liver-related mortality, suggesting that RTx is a feasible option in cirrhotic patients without decompensation, even if they have PH.


Asunto(s)
Hepacivirus , Hepatitis C/cirugía , Trasplante de Riñón/mortalidad , Cirrosis Hepática/cirugía , Adulto , Femenino , Supervivencia de Injerto , Hepatitis C/complicaciones , Hepatitis C/virología , Humanos , Estimación de Kaplan-Meier , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia
20.
PLoS One ; 15(1): e0227445, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31923282

RESUMEN

INTRODUCTION: Thrombotic microangiopathy (TMA) in post-transplant setting has heterogeneous clinical manifestations. METHODS: We retrospectively studied data of 89 patients with post-transplant TMA, which was characterized by thrombi in at least one glomerulus and/or arteriole. Systemic TMA was defined by thrombocytopenia and microangiopathic anemia and early onset TMA, when occurred less than 90 days post transplant. RESULTS: The cumulative incidence was 0.93%. The majority of the recipients were young (mean age 39 years), female (52%) and Caucasian (48%) with primary kidney disease of unknown etiology (37%). Early TMA occurred in 51% of the patients and systemic TMA, in 25%. Underlying precipitating factors were: infection (54%), acute rejection (34%), calcineurin inhibitor toxicity (13%) and pregnancy (3%). 18% of the patients had several triggers. Glomerular TMA was observed in 50% of the biopsies and endothelial cell activation, in 61%. The 1-year patient survival was 97% and corresponding graft survival, 66%. Allograft survival was inferior when acute antibody mediated rejection (ABMR) occurred (with 41%; without 70%, p = 0.01), however no differences were determined by hemolysis, time of onset, thrombi location or endothelial cell activation. CONCLUSIONS: Our results suggest that post-transplant TMA is a rare but severe condition, regardless of its clinical and histological presentation, mainly when associated to ABMR.


Asunto(s)
Trasplante de Riñón/efectos adversos , Microangiopatías Trombóticas/etiología , Adulto , Femenino , Rechazo de Injerto/complicaciones , Rechazo de Injerto/inmunología , Humanos , Incidencia , Infecciones/complicaciones , Enfermedades Renales/complicaciones , Enfermedades Renales/terapia , Masculino , Persona de Mediana Edad , Embarazo , Estudios Retrospectivos , Microangiopatías Trombóticas/patología , Trasplante Homólogo/efectos adversos
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