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1.
Clin Transplant ; 35(6): e14305, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33797134

RESUMO

The current American Society of Transplantation (AST) accredited transplant fellowship programs in the United States provide no structured formal training in leadership and administration which is essential for successfully running a transplant program. We conducted a survey of medical directors of active adult kidney and kidney-pancreas transplant programs in the United States about their demographics, training pathways, and roles and responsibilities. The survey was emailed to 183 medical directors, and 123 (67.2%) completed the survey. A majority of respondents were older than 50 years (61%), males (80%), and holding that position for more than 10 years (47%). Only 51% of current medical directors had taken that position after completing a one-year transplant fellowship, and 58% took on the role with no prior administrative or leadership experience. The medical directors reported spending a median 50%-75% of time in clinical responsibilities, 25%-50% of time in administration, and 0%-25% time in research. The survey also captured various administrative roles of medical directors vis-à-vis other transplant leaders. The study, designed to be the starting point of an improvement initiative of the AST, provided important insight into the demographics, training pathways, roles and responsibilities, job satisfaction, education needs, and training gaps of current medical directors.


Assuntos
Internato e Residência , Diretores Médicos , Adulto , Educação de Pós-Graduação em Medicina , Bolsas de Estudo , Humanos , Rim , Masculino , Pâncreas , Inquéritos e Questionários , Estados Unidos
2.
Am J Transplant ; 20(9): 2491-2498, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32056331

RESUMO

The clinical importance of subclinical, early T cell-mediated rejection (Banff TCMR 1A and borderline lesions) remains unclear, due, in part to the fact that histologic lesions used to characterize early TCMR can be nonspecific. Donor-derived cell-free DNA (dd-cfDNA) is an important molecular marker of active graft injury. Over a study period from June 2017 to May 2019, we assessed clinical outcomes in 79 patients diagnosed with TCMR 1A/borderline rejection across 11 US centers with a simultaneous measurement of dd-cfDNA. Forty-two patients had elevated dd-cfDNA (≥0.5%) and 37 patients had low levels (<0.5%). Elevated levels of dd-cfDNA predicted adverse clinical outcomes: among patients with elevated cfDNA, estimated glomerular filtration rate declined by 8.5% (interquartile rate [IQR] -16.22% to -1.39%) (-3.50 mL/min/1.73 m2 IQR -8.00 to -1.00) vs 0% (-4.92%, 4.76%) in low dd-cfDNA patients (P = .004), de novo donor-specific antibody formation was seen in 40% (17/42) vs 2.7% (P < .0001), and future or persistent rejection occurred in 9 of 42 patients (21.4%) vs 0% (P = .003). The use of dd-cfDNA may complement the Banff classification and to risk stratify patients with borderline/TCMR 1A identified on biopsy.


Assuntos
Ácidos Nucleicos Livres , Transplante de Rim , Aloenxertos , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/etiologia , Humanos , Transplante de Rim/efeitos adversos , Doadores de Tecidos
3.
J Surg Res ; 255: 23-32, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32540577

RESUMO

BACKGROUND: Up to 30% of patients with sickle cell disease (SCD) develop chronic liver disease via etiologies including sickle cell hepatopathy, acquired viral hepatitis, or secondary hemochromatosis. It is unclear how many patients with SCD ultimately undergo liver transplantation (LT) and what factors are associated with survival after LT. In this study, we examined LT outcomes in these patients by reviewing the Scientific Registry of Transplant Recipients (SRTR) and our institutional experience. METHODS: Analysis of the SRTR identified 23 LT recipients and five simultaneous liver and kidney transplantation (SLKT) recipients with SCD. Patient demographics and graft and patient survival were analyzed. Two patients with SCD at our institution underwent SLKT. RESULTS: Review of the SRTR revealed that recipients with SCD had significantly higher model for end-stage liver disease scores (33 versus 21, P = 0.004), preoperative intensive care unit admission (43.5% versus 19.1%, P = 0.007), preoperative dialysis (17.4% versus 4.9%, P = 0.009), and were more likely to be status 1 (26.1% versus 12.1%, P = 0.041) when compared with the reference population of African American LT recipients. Despite being higher risk at the time of LT, patients with SCD had equivalent posttransplant graft and patient survival when compared with the reference population (P = 0.5 and P = 0.2, respectively) and a 2:1 propensity score-matched group (P = 0.5 and P = 0.2, respectively). Two recent SLKT recipients with SCD from our institution have performed well with stable allograft function. CONCLUSIONS: Data from the SRTR demonstrate that patients with SCD can expect equivalent graft and patient survival after LT despite exhibiting more comorbidities at the time of LT. The low number of patients with SCD who underwent LT in the SRTR in comparison with the rate of chronic liver disease in this population raises the question as to whether a disparity in access to LT exists for this complex population.


Assuntos
Anemia Falciforme/terapia , Doença Hepática Terminal/cirurgia , Falência Renal Crônica/terapia , Transplante de Rim/estatística & dados numéricos , Transplante de Fígado/estatística & dados numéricos , Adolescente , Adulto , Negro ou Afro-Americano/estatística & dados numéricos , Anemia Falciforme/complicações , Anemia Falciforme/mortalidade , Criança , Pré-Escolar , Doença Hepática Terminal/etiologia , Doença Hepática Terminal/mortalidade , Feminino , Sobrevivência de Enxerto , Disparidades em Assistência à Saúde/estatística & dados numéricos , Humanos , Falência Renal Crônica/etiologia , Falência Renal Crônica/mortalidade , Masculino , Pessoa de Meia-Idade , Diálise Renal , Estudos Retrospectivos , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto Jovem
4.
Am J Transplant ; 19(11): 3018-3034, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31152476

RESUMO

TRANSFORM (TRANSplant eFficacy and safety Outcomes with an eveRolimus-based regiMen) was a 24-month, prospective, open-label trial in 2037 de novo renal transplant recipients randomized (1:1) within 24 hours of transplantation to receive everolimus (EVR) with reduced-exposure calcineurin inhibitor (EVR + rCNI) or mycophenolate with standard-exposure CNI. Consistent with previously reported 12-month findings, noninferiority of the EVR + rCNI regimen for the primary endpoint of treated biopsy-proven acute rejection (tBPAR) or estimated glomerular filtration rate (eGFR) <50 mL/min per 1.73 m2 was achieved at month 24 (47.9% vs 43.7%; difference = 4.2%; 95% confidence interval = -0.3, 8.7; P = .006). Mean eGFR was stable up to month 24 (52.6 vs 54.9 mL/min per 1.73 m2 ) in both arms. The incidence of de novo donor-specific antibodies (dnDSA) was lower in the EVR + rCNI arm (12.3% vs 17.6%) among on-treatment patients. Although discontinuation rates due to adverse events were higher with EVR + rCNI (27.2% vs 15.0%), rates of cytomegalovirus (2.8% vs 13.5%) and BK virus (5.8% vs 10.3%) infections were lower. Cytomegalovirus infection rates were significantly lower with EVR + rCNI even in the D+/R- high-risk group (P < .0001). In conclusion, the EVR + rCNI regimen offers comparable efficacy and graft function with low tBPAR and dnDSA rates and significantly lower incidence of viral infections relative to standard-of-care up to 24 months. Clinicaltrials.gov number: NCT01950819.


Assuntos
Inibidores de Calcineurina/uso terapêutico , Everolimo/uso terapêutico , Rejeição de Enxerto/mortalidade , Sobrevivência de Enxerto/efeitos dos fármacos , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/mortalidade , Feminino , Seguimentos , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/patologia , Prognóstico , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida
5.
J Am Soc Nephrol ; 29(7): 1979-1991, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29752413

RESUMO

Background Everolimus permits reduced calcineurin inhibitor (CNI) exposure, but the efficacy and safety outcomes of this treatment after kidney transplant require confirmation.Methods In a multicenter noninferiority trial, we randomized 2037 de novo kidney transplant recipients to receive, in combination with induction therapy and corticosteroids, everolimus with reduced-exposure CNI (everolimus arm) or mycophenolic acid (MPA) with standard-exposure CNI (MPA arm). The primary end point was treated biopsy-proven acute rejection or eGFR<50 ml/min per 1.73 m2 at post-transplant month 12 using a 10% noninferiority margin.Results In the intent-to-treat population (everolimus n=1022, MPA n=1015), the primary end point incidence was 48.2% (493) with everolimus and 45.1% (457) with MPA (difference 3.2%; 95% confidence interval, -1.3% to 7.6%). Similar between-treatment differences in incidence were observed in the subgroups of patients who received tacrolimus or cyclosporine. Treated biopsy-proven acute rejection, graft loss, or death at post-transplant month 12 occurred in 14.9% and 12.5% of patients treated with everolimus and MPA, respectively (difference 2.3%; 95% confidence interval, -1.7% to 6.4%). De novo donor-specific antibody incidence at 12 months and antibody-mediated rejection rate did not differ between arms. Cytomegalovirus (3.6% versus 13.3%) and BK virus infections (4.3% versus 8.0%) were less frequent in the everolimus arm than in the MPA arm. Overall, 23.0% and 11.9% of patients treated with everolimus and MPA, respectively, discontinued the study drug because of adverse events.Conclusions In kidney transplant recipients at mild-to-moderate immunologic risk, everolimus was noninferior to MPA for a binary composite end point assessing immunosuppressive efficacy and preservation of graft function.


Assuntos
Inibidores de Calcineurina/administração & dosagem , Everolimo/uso terapêutico , Rejeição de Enxerto/etiologia , Imunossupressores/uso terapêutico , Transplante de Rim , Corticosteroides/uso terapêutico , Adulto , Aloenxertos/fisiopatologia , Ciclosporina/uso terapêutico , Infecções por Citomegalovirus/etiologia , Everolimo/efeitos adversos , Feminino , Taxa de Filtração Glomerular , Rejeição de Enxerto/patologia , Humanos , Terapia de Imunossupressão/métodos , Imunossupressores/efeitos adversos , Análise de Intenção de Tratamento , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Infecções por Polyomavirus/etiologia , Tacrolimo/uso terapêutico , Infecções Tumorais por Vírus/etiologia
6.
Curr Opin Organ Transplant ; 24(1): 92-96, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30507708

RESUMO

PURPOSE OF REVIEW: Kidney transplantation indisputably confers a significant survival advantage and a better quality of life compared with dialysis, however, because of the increasing demand for kidney transplantation many patients continue to wait prolonged periods for kidney transplantation. The first step to alleviate the shortage is to reduce the discard rate by utilizing more marginal kidneys. This review studied the recent literature on marginal kidney transplantation. RECENT FINDINGS: More than 60% of high-KDPI kidneys are discarded. Despite the increase in posttransplant costs, use of high KDPI transplants suggests a gain in survival years, thus making marginal kidney transplant cost effective. Furthermore, recent evidence suggests that marginal kidney transplantation shows a survival benefit compared with remaining in the waitlist and minimizes the kidney discard rate. SUMMARY: Transplantation with marginal kidneys provides a survival benefit over dialysis or waiting for a low-KDPI kidney. As a result, clinicians should strongly consider transplantation of marginal kidneys as opposed to waiting for a better offer.


Assuntos
Transplante de Rim/métodos , Feminino , Humanos , Masculino
7.
Curr Opin Organ Transplant ; 24(1): 82-86, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30540574

RESUMO

PURPOSE OF REVIEW: Delayed graft function (DGF) has several long-term graft implications in the field of kidney transplantation and remains a challenge. The incidence of DGF is on the rise because of an increasing use of marginal kidneys in an era of organ shortage. Risk factors for DGF are numerous and stem from multiple sources in the transplant chain starting from the donor to its final allocation in the recipient. There is no FDA-approved therapy for DGF, and several therapies are being studied to mitigate ischemic injury and prolong graft survival. RECENT FINDINGS: Published data from studies suggest that ischemia-reperfusion injury (IRI) and immune responses to transplants are the leading cause of DGF, which in turn is associated with an increased incidence in acute renal rejection. Several novel methods are being developed and are undergoing further clinical validation to prove as an effective therapy against DGF. SUMMARY: Recent studies have proposed several different mechanisms to mitigate ischemic injury to prevent acute renal injury, both of which are representative of DGF. New therapies must be effectively reviewed to ensure advancement of DGF prevention. A number of immunotherapies targeted towards inhibition of complement activation in addition to other novel therapies might prove promising towards mitigating DGF.


Assuntos
Função Retardada do Enxerto/etiologia , Transplante de Rim/efeitos adversos , Função Retardada do Enxerto/patologia , Feminino , Humanos , Masculino , Fatores de Risco
8.
Clin Transplant ; 31(9)2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28504869

RESUMO

Kidney transplant in patients with liver cirrhosis and nondialysis chronic kidney disease (CKD) is controversial. We report 14 liver cirrhotic patients who had persistently low MDRD-6 estimated glomerular filtration rate (e-GFR) <40 mL/min/1.73 m2 for ≥3 months and underwent either liver transplant alone (LTA; n=9) or simultaneous liver-kidney transplant (SLKT; n=5). Pretransplant, patients with LTA compared with SLKT had lower serum creatinine (2.5±0.73 vs 4.6±0.52 mg/dL, P=.001), higher MDRD-6 e-GFR (21.0±7.2 vs 10.3±2.0 mL/min/1.73 m2 , P=.002), higher 24-hour urine creatinine clearance (34.2±8.8 vs 18.0±2.2 mL/min, P=.002), lower proteinuria (133.2±117.7 vs 663±268.2 mg/24 h, P=.0002), and relatively normal kidney biopsy and ultrasound findings. Post-LTA, the e-GFR (mL/min/1.73 m2 ) increased in all nine patients, with mean e-GFR at 1 month (49.8±8.4), 3 months (49.6±8.7), 6 months (49.8±8.1), 12 months (47.6±9.2), 24 months (47.9±9.1), and 36 months (45.1±7.3) significantly higher compared to pre-LTA e-GFR (P≤.005 at all time points). One patient developed end-stage renal disease 9 years post-LTA and another patient expired 7 years post-LTA. The low e-GFR alone in the absence of other markers or risk factors of CKD should not be an absolute criterion for SLKT in patients with liver cirrhosis.


Assuntos
Doença Hepática Terminal/cirurgia , Cirrose Hepática/complicações , Transplante de Fígado , Insuficiência Renal Crônica/complicações , Adulto , Idoso , Tomada de Decisão Clínica , Doença Hepática Terminal/complicações , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/fisiopatologia , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Estudos Retrospectivos , Transplante Homólogo , Resultado do Tratamento
9.
Clin Transplant ; 30(2): 118-23, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26529140

RESUMO

Hispanic race and low socioeconomic status are established predictors of disparity in access to kidney transplantation. This single-center retrospective review was undertaken to determine whether Hispanic race predicted kidney transplant outcomes. A total of 720 patients underwent kidney transplantation from January 1, 2004 to December 31, 2013, including 398 Hispanic patients and 322 non-Hispanic patients. Hispanic patients were significantly younger (p < 0.0001), on hemodialysis for longer (p = 0.0018), had a greater percentage with public insurance (p < 0.0001), more commonly had diabetes as the cause of end-stage renal disease (p = 0.0167), and had a lower percentage of living donors (p = 0.0013) compared to non-Hispanic patients. There was no difference in one-, five-, and 10-yr graft (97%, 81%, and 61% vs. 95%, 76%, and 42% p = 0.18) or patient survival (98%, 90%, and 84% vs. 97%, 87%, and 69% p = 0.11) between the Hispanic and non-Hispanic recipients. Multivariate analysis identified increased recipient age and kidney donor profile index to be predictive of lower graft survival and increasing recipient age to be predictive of lower patient survival. In the largest single-center study on kidney transplantation outcomes in Hispanic patients, there is no difference in graft and recipient survival between Hispanic and non-Hispanic kidney transplant patients, and in multivariate analysis, Hispanic race is not a risk factor for graft or patient survival.


Assuntos
Rejeição de Enxerto/epidemiologia , Hispânico ou Latino/estatística & dados numéricos , Transplante de Rim/estatística & dados numéricos , Doadores Vivos , Complicações Pós-Operatórias , Adulto , Fatores Etários , California/epidemiologia , Estudos de Casos e Controles , Etnicidade/estatística & dados numéricos , Feminino , Seguimentos , Taxa de Filtração Glomerular , Sobrevivência de Enxerto , Humanos , Falência Renal Crônica/cirurgia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco
10.
Ethn Health ; 21(1): 58-70, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-25650806

RESUMO

OBJECTIVES: Culturally relevant education is needed to improve rates of successful kidney transplantation among Hispanic patients with end-stage renal disease (ESRD). This study examined whether patients' knowledge about kidney disease, postoperative care, and proactive health practices improved after watching a telenovela series about ESRD. DESIGN: 334 ESRD patients and 94 family members/caregivers were assigned to watch a telenovela ('Fixing Paco,' a bilingual health education film) or receive standard of care at a transplant center or at a dialysis clinic. Outcomes for pre-transplant patients assigned to standard of care at dialysis centers or at a transplant center were compared to pre-transplant patients in the treatment condition (standard of care + telenovela). RESULTS: Knowledge and behavioral intention scores at baseline across conditions and locations were similar, suggesting that assignment resulted in comparable groups at baseline. Using linear regression, this study found statistically significant improvements in knowledge scores among the telenovela group as compared to the standard of care groups. The telenovela group also had greater improvements in behavioral intention scores compared to the standard of care groups. Family members assigned to the telenovela group had significant improvements in knowledge scores as compared to the standard of care groups. CONCLUSION: Being well informed about ESRD and adopting proactive health behaviors are important mechanisms in improving transplantation outcomes. These findings suggest that knowledge about kidney disease, postoperative care, and proactive health practices could be improved by viewing a telenovela. Implications, limitations, and directions for future research are discussed.


Assuntos
Educação em Saúde/métodos , Conhecimentos, Atitudes e Prática em Saúde , Hispânico ou Latino/psicologia , Intenção , Falência Renal Crônica/terapia , Gravação em Vídeo , Adulto , California , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Televisão
11.
Curr Opin Organ Transplant ; 20(6): 652-6, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26536428

RESUMO

PURPOSE OF REVIEW: The purpose of this review is to evaluate the effectiveness of bortezomib in the recent literature for the prevention and treatment of kidney transplant rejection. RECENT FINDINGS: Several studies have analyzed bortezomib alone and in comparison to more traditional immunosuppressive agents during the last 2 years. If administered prior to transplant or soon thereafter, bortezomib appears to lower donor-specific antibody levels and improves graft survival. Its role as a treatment option for antibody-mediated rejection after transplant remains unclear, with limited evidence supporting its long-term success. SUMMARY: Bortezomib appears to be a promising early desensitizing agent in the world of kidney transplantation and high short-term success rates have been observed. However, additional randomized trials would be useful to more conclusively demonstrate its effectiveness and optimal administration time in relation to transplant surgery.


Assuntos
Bortezomib/uso terapêutico , Imunossupressores/uso terapêutico , Transplante de Rim , Animais , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
J Med Virol ; 83(12): 2128-34, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22012720

RESUMO

A small percentage of renal patients become infected with the BK polyomavirus (BKV), a pathogenic virus that causes BKV-associated nephropathy (BKVN), after kidney transplantation. This study presents a simple, rapid, high-throughput method for BKV genotyping using high-resolution melt analysis (HRMA). Using this novel method, BKV genotypes were analyzed in 49 samples taken from BKV-positive renal transplantation patients for classification into 1 of 3 genotypes: GI-1 (subgroups Ia, Ib1, and Ic), GI-2 (subgroup Ib2), and GII-IV (subtypes II, III, and IV). HRMA was performed to compare each sample sequence to a reference sequence that contained a combination of 2 of the 3 genotype groups, and the findings validated by conventional DNA sequencing. Of the 49 samples, 20 samples were classified as GI-1, 18 as GI-2, and 11 as GII-IV, suggesting that the predominant BKV strain (77.6%) in these patients was subtype I (GI-1 and GI-2). The HRMA method presented here is a time-saving, reliable, and low-cost procedure that can be developed as a diagnostic tool in the detection of the specific BKV genotypes associated with BKVN.


Assuntos
Vírus BK/classificação , Vírus BK/genética , Tipagem Molecular/métodos , Temperatura de Transição , Virologia/métodos , Vírus BK/isolamento & purificação , DNA Viral/química , DNA Viral/genética , Genótipo , Humanos , Transplante de Rim , Infecções por Polyomavirus/virologia , Análise de Sequência de DNA , Transplante
13.
Ther Drug Monit ; 33(1): 45-9, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21099740

RESUMO

OBJECTIVE: The aim of the study is to characterize the pharmacokinetics and the gastrointestinal side effect profiles of enteric-coated mycophenolate sodium (EC-MPS) in de novo kidney transplant patients of Hispanic ethnicity. MATERIALS AND METHODS: The pharmacokinetic study of EC-MPS was conducted in 11 de novo kidney transplant patients of Hispanic ethnicity. Eight blood samples were obtained after EC-MPS was given at the steady state. Blood concentrations of mycophenolic acid (MPA) and its glucuronide metabolite (MPAG) were measured. RESULTS: The mean age (± standard deviation) was 39.4 (± 12.3) years. The mean daily dose of EC-MPS at the time of the pharmacokinetic study was 1408 ± 108 mg. For MPA and MPAG, the time to peak concentration was 2.5 ± 1.3 hours and 4.6 ± 3.1 hours, respectively; the peak concentration (Cmax) was 19.3 ± 17.2 mg/L and 109.4 ± 49.2 mg/L; and the area under the curve from 6 to 12 hours (AUC6-12) was 32.2 ± 19.3 mg·hr/L and 373.7 ± 235.8 mg·hr/L, respectively, which represents 41.3% and 43.0% of AUC0-12. The AUC0-12 for MPA measured 77.8 ± 53.1 mg·hr/L and for MPAG 869.2 ± 388.8 mg·hr/L. Seven patients (64%) exhibited a second peak at approximately 8.3 hours after the dose at a mean concentration (± standard deviation) of 10.3 ± 7.6 mg/L. The Cmax or AUC of MPA does not correlate with overall Gastrointestinal Symptom Rating Scale scores or subscale scores, but the Cmax of MPAG correlates with indigestion subscale (P = 0.022), diarrhea (P = 0.032), and overall scores (P = 0.028). The AUC of MPAG also correlates with acid reflux (P = 0.024) and indigestion (P = 0.032). DISCUSSION AND CONCLUSION: The pharmacokinetics of EC-MPS has a high variability in de novo kidney transplant patients of the Hispanic ethnicity, which was similar to other ethnic groups. The MPA exposure expressed by the AUC appears to be higher in Hispanic patients than those reported in other ethnic groups, which may be the result of various factors such as difference of the uridine diphosphate glucuronosyltransferase enzyme genotypes, but gastrointestinal side effects were acceptable and the Cmax or AUC of MPAG showed correlations with gastrointestinal symptoms.


Assuntos
Trato Gastrointestinal/efeitos dos fármacos , Imunossupressores/efeitos adversos , Imunossupressores/farmacocinética , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/farmacocinética , Adulto , Idoso , Área Sob a Curva , Etnicidade , Feminino , Glucuronídeos/farmacocinética , Hispânico ou Latino , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/sangue , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/sangue , Prednisona/uso terapêutico , Comprimidos com Revestimento Entérico/administração & dosagem , Tacrolimo/uso terapêutico , População Branca
14.
Ann Transplant ; 26: e932249, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34210952

RESUMO

Kidney transplant recipients require meticulous clinical and laboratory surveillance to monitor allograft health. Conventional biomarkers, including serum creatinine and proteinuria, are lagging indicators of allograft injury, often rising only after significant and potentially irreversible damage has occurred. Immunosuppressive medication levels can be followed, but their utility is largely limited to guiding dosing changes or assessing adherence. Kidney biopsy, the criterion standard for the diagnosis and characterization of injury, is invasive and thus poorly suited for frequent surveillance. Donor-derived cell-free DNA (dd-cfDNA) is a sensitive, noninvasive, leading indicator of allograft injury, which offers the opportunity for expedited intervention and can improve long-term allograft outcomes. This article describes the clinical rationale for a routine testing schedule utilizing dd-cfDNA surveillance at months 1, 2, 3, 4, 6, 9, and 12 during the first year following kidney transplantation and quarterly thereafter. These time points coincide with major immunologic transition points after transplantation and provide clinicians with molecular information to help inform decision making.


Assuntos
Ácidos Nucleicos Livres , Transplante de Rim , Rejeição de Enxerto/diagnóstico , Humanos , Transplante de Rim/efeitos adversos , Doadores de Tecidos , Transplantados
15.
Transplant Proc ; 53(10): 2866-2872, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34774309

RESUMO

BACKGROUND: Donor-derived cell-free DNA (dd-cfDNA) in plasma is an established noninvasive biomarker for allograft injury and rejection. A single-nucleotide polymorphism (SNP)-based massively multiplexed polymerase chain reaction methodology can be used to quantify dd-cfDNA in kidney transplant recipients. In this study we describe our clinical experience in using a SNP-based dd-cfDNA assay for the management of active rejection in renal transplant recipients. METHODS: To assess the clinical utility of a clinically available SNP-based massively multiplexed polymerase chain reaction dd-cfDNA assay, we analyzed biopsy data contemporaneous to dd-cfDNA results at 33 participating clinics and calculated the rate of rejection in dd-cfDNA-matched biopsy results. RESULTS: A total of 1347 dd-cfDNA test samples from 879 patients were accessioned from October 3, 2019, to November 2, 2020. The dd-cfDNA testing classified 25.2% (340/1347) of samples as high-risk (dd-cfDNA fraction ≥ 1%). Clinical follow-up was available for 32.1% (109/340) of the high-risk results, which included samples from 28 patients with definitive biopsy results within 2 weeks of dd-cfDNA testing. Pathology reports indicated a 64% (18/28) rate of active rejection in biopsy result-matched samples. Total cfDNA measurements indicated a skewed distribution and a correlation with dd-cfDNA-derived patient risk classification. CONCLUSIONS: This is the first report showing the impact of dd-cfDNA on patient management in a multicenter real-world clinical cohort. The data indicate that incorporating dd-cfDNA testing into practice may improve physician decision making regarding renal allograft recipients.


Assuntos
Ácidos Nucleicos Livres , Transplante de Rim , Aloenxertos , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/genética , Humanos , Transplante de Rim/efeitos adversos , Doadores de Tecidos
16.
Virol J ; 7: 295, 2010 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-21034442

RESUMO

BACKGROUND: BK virus infections can have clinically significant consequences in immunocompromised individuals. Detection and monitoring of active BK virus infections in certain situations is recommended and therefore PCR assays for detection of BK virus have been developed. The performance of current BK PCR detection assays is limited by the existence of viral polymorphisms, unknown at the time of assay development, resulting in inconsistent detection of BK virus. The objective of this study was to identify a stable region of the BK viral genome for detection by PCR that would be minimally affected by polymorphisms as more sequence data for BK virus becomes available. RESULTS: Employing a combination of techniques, including amino acid and DNA sequence alignment and interspecies analysis, a conserved, stable PCR target region of the BK viral genomic region was identified within the VP2 gene. A real-time quantitative PCR assay was then developed that is specific for BK virus, has an analytical sensitivity of 15 copies/reaction (450 copies/ml) and is highly reproducible (CV ≤ 5.0%). CONCLUSION: Identifying stable PCR target regions when limited DNA sequence data is available may be possible by combining multiple analysis techniques to elucidate potential functional constraints on genomic regions. Applying this approach to the development of a real-time quantitative PCR assay for BK virus resulted in an accurate method with potential clinical applications and advantages over existing BK assays.


Assuntos
Vírus BK/isolamento & purificação , DNA Viral/isolamento & purificação , Reação em Cadeia da Polimerase/métodos , Infecções por Polyomavirus/diagnóstico , Virologia/métodos , Vírus BK/genética , Sequência Conservada , DNA Viral/genética , Humanos , Polimorfismo Genético , Infecções por Polyomavirus/virologia , Sensibilidade e Especificidade , Alinhamento de Sequência
17.
Curr Opin Organ Transplant ; 20(6): 629, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26536424
18.
Transpl Immunol ; 20(3): 113-7, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18996198

RESUMO

BACKGROUND: Antibody Mediated Rejection (AMR) is a major cause of early graft loss, graft dysfunction, and chronic allograft nephropathy. Patients with elevated pre-transplant Panel Reactive Antibodies (PRA) are at much higher risk to develop AMR. We, retrospectively, studied the attack rate of AMR in sensitized recipients and evaluated whether preformed antibodies to donor Cross Reactive Epitope Group (CREG) and/or choice of induction immunosuppressive agent affected the frequency of this complication. METHODS: From the period between September 2002 and March 2008, we identified 19 sensitized renal transplant recipients (with mean PRA of 44.5+/-26%) and recorded the induction agent, number of HLA antigen mismatches, CREG match, CREG antibodies, PRA levels, clinical course, biopsy proven rejection episodes and presence of donor specific antibody. Nine patients were induced with Alemtuzumab (Campath-1H) and ten received horse or rabbit derived polyclonal antithymocyte antibody ATGAM (Pharmacia) or Thymoglobulin (Genzyme). All recipients were cross-match negative at time of transplant. RESULTS: Out of the 19 patients, 9 patients developed acute rejection (47.4%), 4 had AMR and 5 had Acute Cellular Rejection (ACR). Out of 19 patients, 9 patients had existing CREG antibodies (as per CREG Model proposed by McKenna, Takemoto et al.). All patients who developed AMR were found of have preformed antibodies to donor CREG. The median time interval for the development of acute humoral rejection was only 6 days and biopsies showed acute vascular rejection with Complement (C(4)D) deposition. CONCLUSIONS: Pre-existing CREG antibodies in sensitized renal transplant patients appear to identify a group at high risk to develop AMR.


Assuntos
Anticorpos Monoclonais/imunologia , Epitopos , Rejeição de Enxerto/imunologia , Transplante de Rim/imunologia , Adulto , Negro ou Afro-Americano , Idoso , Reações Cruzadas , Feminino , Humanos , Terapia de Imunossupressão , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , População Branca , Adulto Jovem
19.
Curr Opin Organ Transplant ; 14(2): 201-5, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19300256

RESUMO

PURPOSE OF REVIEW: The number of organs available for the patients on the transplant waitlist remains at a disproportionate low. All possible methods to curtail this shortage, including providing donors with incentives, have been proposed. This article reviews recent publications addressing the benefits and risks involved in incentivizing living donation. RECENT FINDINGS: The debate about the ethics, feasibility, and possible models for compensating organ donors has been prominent in recent literature. As certain countries take lead on this initiative, others are cautiously weighing in on the impact implementations of such policies may have on the society, especially on the underprivileged. SUMMARY: The shortage of organs has resulted in proposal of strategies that encroach on certain moral and ethical principles. Providing incentives to donors is one such strategy that is likely to receive a lot of attention in the next few years.


Assuntos
Doadores Vivos , Motivação , Transplante de Órgãos , Comércio , Compensação e Reparação , Regulamentação Governamental , Política de Saúde , Acessibilidade aos Serviços de Saúde , Humanos , Irã (Geográfico) , Doadores Vivos/ética , Doadores Vivos/legislação & jurisprudência , Doadores Vivos/provisão & distribuição , Transplante de Órgãos/economia , Transplante de Órgãos/ética , Transplante de Órgãos/legislação & jurisprudência , Fatores Socioeconômicos , Obtenção de Tecidos e Órgãos/economia , Obtenção de Tecidos e Órgãos/ética , Obtenção de Tecidos e Órgãos/legislação & jurisprudência , Estados Unidos , Listas de Espera
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