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1.
Circulation ; 148(7): 622-636, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37439224

RESUMO

Although heart transplantation is the preferred therapy for appropriate patients with advanced heart failure, the presence of concomitant renal or hepatic dysfunction can pose a barrier to isolated heart transplantation. Because donor organ supply limits the availability of organ transplantation, appropriate allocation of this scarce resource is essential; thus, clear guidance for simultaneous heart-kidney transplantation and simultaneous heart-liver transplantation is urgently required. The purposes of this scientific statement are (1) to describe the impact of pretransplantation renal and hepatic dysfunction on posttransplantation outcomes; (2) to discuss the assessment of pretransplantation renal and hepatic dysfunction; (3) to provide an approach to patient selection for simultaneous heart-kidney transplantation and simultaneous heart-liver transplantation and posttransplantation management; and (4) to explore the ethics of multiorgan transplantation.

2.
Ann Pharmacother ; : 10600280241237534, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38501850

RESUMO

OBJECTIVE: The article reviews the safety and efficacy of treatments for cytomegalovirus (CMV) in solid organ transplantation. DATA SOURCES: A literature review was conducted in PubMed, MEDLINE, and Clinicaltrials.gov from database inception through January 2024, using terms CMV, therapy, and solid organ transplantation. STUDY SELECTION AND DATA EXTRACTION: Clinical trials, meta-analyses, cohort studies, case reports, and guidelines were included. Letters to the editor, reviews, and commentaries were excluded. DATA SYNTHESIS: After abstract screening and full-text review of 728 citations for eligibility, 53 were included. Valganciclovir and intravenous ganciclovir are drugs of choice for CMV management and, until recently, the availability of alternative options has been restricted due to toxicity. For instance, foscarnet and cidofovir serve as second-line agents due to potential bone marrow and renal toxicity. In patients with refractory or resistant CMV, maribavir, a novel oral agent, has proven efficacy and a lower adverse effect profile. However, in refractory or resistant CMV, foscarnet and cidofovir are preferred in invasive disease (CMV gastritis, CMV retinitis, and CMV encephalitis), high viral loads, and inability to tolerate oral preparations. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Consensus guidelines have not been revised since approval of novel antivirals in solid organ transplantation. Valganciclovir and ganciclovir remain drugs of choice for initial CMV therapy. Foscarnet, cidofovir, and maribavir are treatments for refractory or resistant-CMV. CONCLUSIONS: Selection of CMV antiviral treatment should be determined by patient-specific factors, including severity of illness, resistant or refractory disease, dose-limiting adverse effects, and the preferred route of administration.

3.
Transpl Infect Dis ; 26(2): e14237, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38341645

RESUMO

BACKGROUND: BK polyomavirus (BKV) can cause permanent loss of allograft function due to BKV-associated nephropathy (BKVN) in kidney transplant recipients. Besides immunosuppression reduction, there are no consistently effective interventions for BKV infection. Study purpose was to define natural history of BKV infection, identify risk factors for BKV reactivation and BKVN in kidney transplant recipients, and inform the design/conduct of future clinical trials of BKV-targeted therapeutics. METHODS: We conducted a multicenter prospective observational study of incident kidney transplant recipients at six U.S. transplant centers. Participants were monitored every 4 weeks for BKV reactivation and followed for up to 24 months post-transplant. We used regression models (logistic, survival, mixed models) to study relationships between BK viremia/BKVN, clinical characteristics, and allograft function. RESULTS: We enrolled 335 participants. Fifty-eight (17%) developed BK viremia, 6 (2%) developed biopsy-proven BKVN, and 29 (9%) developed suspected/presumed BKVN (defined as BKV viral load > 10,000 copies/mL without biopsy). Male donor sex was associated with lower odds for BK viremia, whereas recipient Black race was associated with two-fold increased odds for BK viremia. Recipient female sex was associated with more rapid clearance of BK viremia. Persistent BK viremia/BKVN was associated with poorer allograft function by 24 months post-transplant. CONCLUSIONS: We identified multiple donor and recipient demographic factors associated with risk for BKV infection and poorer allograft function by 24 months post-transplant. This may help design future clinical trials of therapies to prevent or mitigate the deleterious impact of BKV reactivation on kidney transplant outcomes.


Assuntos
Vírus BK , Nefropatias , Transplante de Rim , Infecções por Polyomavirus , Infecções Tumorais por Vírus , Humanos , Masculino , Feminino , Transplante de Rim/efeitos adversos , Estudos Prospectivos , Viremia/complicações , Infecções por Polyomavirus/complicações , Infecções Tumorais por Vírus/tratamento farmacológico
4.
J Am Soc Nephrol ; 34(1): 145-159, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36195441

RESUMO

BACKGROUND: Ischemia-reperfusion (IR) of a kidney transplant (KTx) upregulates TNF α production that amplifies allograft inflammation and may negatively affect transplant outcomes. METHODS: We tested the effects of blocking TNF peri-KTx via a randomized, double-blind, placebo-controlled, 15-center, phase 2 clinical trial. A total of 225 primary transplant recipients of deceased-donor kidneys (KTx; 38.2% Black/African American, 44% White) were randomized to receive intravenous infliximab (IFX) 3 mg/kg or saline placebo (PLBO) initiated before kidney reperfusion. All patients received rabbit anti-thymocyte globulin induction and maintenance immunosuppression (IS) with tacrolimus, mycophenolate mofetil, and prednisone. The primary end point was the difference between groups in mean 24-month eGFR. RESULTS: There was no difference in the primary end point of 24-month eGFR between IFX (52.45 ml/min per 1.73 m 2 ; 95% CI, 48.38 to 56.52) versus PLBO (57.35 ml/min per 1.73 m 2 ; 95% CI, 53.18 to 61.52; P =0.1). There were no significant differences between groups in rates of delayed graft function, biopsy-proven acute rejection (BPAR), development of de novo donor-specific antibodies, or graft loss/death. Immunosuppression did not differ, and day 7 post-KTx plasma analyses showed approximately ten-fold lower TNF ( P <0.001) in IFX versus PLBO. BK viremia requiring IS change occurred more frequently in IFX (28.9%) versus PLBO (13.4%; P =0.004), with a strong trend toward higher rates of BKV nephropathy in IFX (13.3%) versus PLBO (4.9%; P =0.06). CONCLUSIONS: IFX induction therapy does not benefit recipients of kidney transplants from deceased donors on this IS regimen. Because the intervention unexpectedly increased rates of BK virus infections, our findings underscore the complexities of targeting peritransplant inflammation as a strategy to improve KTx outcomes.Clinical Trial registry name and registration number:clinicaltrials.gov (NCT02495077).


Assuntos
Vírus BK , Transplante de Rim , Viroses , Humanos , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Transplante de Rim/métodos , Infliximab/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Inflamação/tratamento farmacológico , Viroses/tratamento farmacológico
5.
Clin Infect Dis ; 75(7): 1210-1216, 2022 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-35100619

RESUMO

BACKGROUND: BK polyomavirus (BKPyV) infection and BK polyomavirus nephropathy (BKPyVAN) are important causes of allograft dysfunction and premature allograft loss in renal transplant recipients. RESULTS AND DISCUSSION: Controlled clinical trials to evaluate new agents for prevention and treatment are needed but are hampered by the lack of outcome measures that accurately assess the effect of the intervention, are clinically relevant, and are acceptable from a regulatory perspective. METHODS: To facilitate consistent end points in clinical trials and to support clinical research and drug development, definitions of BKPyV infection and disease have been developed by the BK Disease Definitions Working Group of the Transplantation Associated Virus Infection Forum with the Forum for Collaborative Research, which consists of scientists, clinicians, regulators, and industry representatives. CONCLUSIONS: These definitions refine established principles of "proven" BKPyV disease and introduce a "probable" disease category that could be used in clinical trials to prevent or treat BKPyVAN in renal transplant recipients.


Assuntos
Vírus BK , Nefropatias , Transplante de Rim , Infecções por Polyomavirus , Ensaios Clínicos como Assunto , Consenso , Humanos , Transplante de Rim/efeitos adversos , Infecções por Polyomavirus/diagnóstico , Infecções por Polyomavirus/etiologia , Transplantados
6.
Transpl Int ; 35: 10448, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35721467

RESUMO

The routine surveillance of kidney transplant allografts has relied on imperfect non-invasive biomarkers such as creatinine and urinary indices, while the gold standard allograft biopsy is associated with risk of bleeding, organ injury and sampling errors. Donor derived cell free DNA (dd-cfDNA) is being employed as a biomarker that addresses limitations of these surveillance methods, albeit has inherent drawbacks. This review provides an update on the enhanced understanding of dd-cfDNA and its expanded use beyond the conventional indication of detecting allograft rejection.


Assuntos
Ácidos Nucleicos Livres , Transplante de Rim , Biomarcadores , Rejeição de Enxerto/diagnóstico , Humanos , Transplante de Rim/efeitos adversos , Doadores de Tecidos
7.
Am J Transplant ; 21(1): 37-43, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33405318

RESUMO

Kidney transplant is a life-changing procedure, and transplant nephrologists, as part of a larger transplant team, play an important role in the field by managing the complex medical needs of transplant patients. The subspecialty of transplant nephrology, however, faces structural challenges related to its workforce, reporting structures, compensation, research and innovation, and health care information technology. The position of transplant nephrology at the academic and operational intersection of medicine and surgery may limit its access to critical resources, hinder academic promotion, and contribute to physician burnout. The authors provide an overview of the subspecialty transplant nephrology and propose solutions. Collaborative efforts that fortify the subspecialty of transplant nephrology will ultimately improve the lives of patients suffering from kidney disease.


Assuntos
Nefropatias , Transplante de Rim , Nefrologia , Previsões , Humanos , Recursos Humanos
8.
Am J Transplant ; 21(8): 2824-2832, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33346917

RESUMO

Current short-term kidney post-transplant survival rates are excellent, but longer-term outcomes have historically been unchanged. This study used data from the national Scientific Registry of Transplant Recipients (SRTR) and evaluated 1-year and 5-year graft survival and half-lives for kidney transplant recipients in the US. All adult (≥18 years) solitary kidney transplants (n = 331,216) from 1995 to 2017 were included in the analysis. Mean age was 49.4 years (SD +/-13.7), 60% male, and 25% Black. The overall (deceased and living donor) adjusted hazard of graft failure steadily decreased from 0.89 (95%CI: 0.88, 0.91) in era 2000-2004 to 0.46 (95%CI: 0.45, 0.47) for era 2014-2017 (1995-1999 as reference). Improvements in adjusted hazards of graft failure were more favorable for Blacks, diabetics and older recipients. Median survival for deceased donor transplants increased from 8.2 years in era 1995-1999 to an estimated 11.7 years in the most recent era. Living kidney donor transplant median survival increased from 12.1 years in 1995-1999 to an estimated 19.2 years for transplants in 2014-2017. In conclusion, these data show continuous improvement in long-term outcomes with more notable improvement among higher-risk subgroups, suggesting a narrowing in the gap for those disadvantaged after transplantation.


Assuntos
Transplante de Rim , Transplantes , Adulto , Feminino , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Rim , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Sistema de Registros
9.
Am J Transplant ; 21(7): 2498-2508, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33284498

RESUMO

Immunosuppression and comorbidities might place solid organ transplant (SOT) recipients at higher risk from COVID-19, as suggested by recent case series. We compared 45 SOT vs. 2427 non-SOT patients who were admitted with COVID-19 to our health-care system (March 1, 2020 - August 21, 2020), evaluating hospital length-of-stay and inpatient mortality using competing-risks regression. We compared trajectories of WHO COVID-19 severity scale using mixed-effects ordinal logistic regression, adjusting for severity score at admission. SOT and non-SOT patients had comparable age, sex, and race, but SOT recipients were more likely to have diabetes (60% vs. 34%, p < .001), hypertension (69% vs. 44%, p = .001), HIV (7% vs. 1.4%, p = .024), and peripheral vascular disorders (19% vs. 8%, p = .018). There were no statistically significant differences between SOT and non-SOT in maximum illness severity score (p = .13), length-of-stay (sHR: 0.9 1.11.4 , p = .5), or mortality (sHR: 0.1 0.41.6 , p = .19), although the severity score on admission was slightly lower for SOT (median [IQR] 3 [3, 4]) than for non-SOT (median [IQR] 4 [3-4]) (p = .042) Despite a higher risk profile, SOT recipients had a faster decline in disease severity over time (OR = 0.76 0.810.86 , p < .001) compared with non-SOT patients. These findings have implications for transplant decision-making during the COVID-19 pandemic, and insights about the impact of SARS-CoV-2 on immunosuppressed patients.


Assuntos
COVID-19 , Transplante de Órgãos , Humanos , Pacientes Internados , Transplante de Órgãos/efeitos adversos , Pandemias , Estudos Retrospectivos , SARS-CoV-2 , Transplantados
10.
Clin Transplant ; 35(9): e14402, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34184326

RESUMO

BACKGROUND: Donor-derived cell-free DNA (dd-cfDNA) is a marker of allograft injury in transplant recipients; however, the relationship between dd-cfDNA and other clinical parameters associated with adverse allograft outcomes is not well-characterized. METHODS: We performed a retrospective analysis of kidney transplant recipients from the DART cohort (ClinicalTrials.gov Identifier: NCT02424227) to evaluate the associations between eGFR decline, de novo donor-specific antibodies (dnDSA), and dd-cfDNA. RESULTS: Both elevated dd-cfDNA (≥1%) and dd-cfDNA variability (≥.34%) in the first post-transplant year were associated with decline in eGFR ≥25% in the second year (21.4% vs. 4.1%, P = .005; 25% vs. 3.6%, P = .002, respectively). Compared to samples from DSA negative patients, samples from patients with concurrent de novo HLA DSAs had higher dd-cfDNA levels (P < .0001). DISCUSSION: Abnormalities in dd-cfDNA levels are associated with clinical parameters commonly used as surrogate endpoints for adverse allograft outcomes, raising the possibility that molecular injury as characterized by dd-cfDNA could help identify patients at risk of these outcomes.


Assuntos
Ácidos Nucleicos Livres , Transplante de Rim , Rejeição de Enxerto/etiologia , Antígenos HLA , Humanos , Isoanticorpos , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Doadores de Tecidos
11.
Clin Transplant ; 35(10): e14425, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34272777

RESUMO

BACKGROUND: Younger kidney transplant (KT) candidates and recipients may have cognitive impairment due to chronic diseases and reliance on dialysis. METHODS: To quantify cognitive impairment burden by age across the KT care continuum, we leveraged a two-center cohort study of 3854 KT candidates at evaluation, 1114 recipients at admission, and 405 recipients at 1-year post-KT with measured global cognitive performance (3MS) or executive function (Trail Making Test). We also estimated burden of severe cognitive impairment that affects functional dependence (activities of daily living [ADL] < 6 or instrumental activities of daily living [IADL] < 8). RESULTS: Among KT candidates, global cognitive impairment (18-34 years: 11.1%; 35-49 years: 14.0%; 50-64 years: 19.5%; ≥65 years: 22.0%) and severe cognitive impairment burden (18-34 years: 1.1%; 35-49 years: 3.0%; 50-64 years: 6.2%; ≥65 years: 7.7%) increased linearly with age. Among KT recipients at admission, global cognitive impairment (18-34 years: 9.1%; 35-49 years: 6.1%; 50-64 years: 9.3%; ≥65 years: 15.7%) and severe cognitive impairment burden (18-34 years: 1.4%; 35-49 years: 1.4%; 50-64 years: 2.2%; ≥65 years: 4.6%) was lower. Despite lowest burden of cognitive impairment among KT recipients at 1-year post-KT across all ages (18-34 years: 1.7%; 35-49 years: 3.4%; 50-64 years: 4.3%; ≥65 years: 6.5%), many still exhibited severe cognitive impairment (18-34 years: .0%; 35-49 years: 1.9%; 50-64 years: 2.4%; ≥65 years: 3.5%). CONCLUSION: Findings were consistent for executive function impairment. While cognitive impairment increases with age, younger KT candidates have a high burden comparable to community-dwelling older adults, with some potentially suffering from severe forms. Transplant centers should consider routinely screening patients during clinical care encounters regardless of age.


Assuntos
Disfunção Cognitiva , Transplante de Rim , Atividades Cotidianas , Adolescente , Adulto , Idoso , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Estudos de Coortes , Humanos , Transplante de Rim/efeitos adversos , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
12.
Transpl Int ; 34(8): 1530-1541, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34129713

RESUMO

Allografts from living kidney donors with hypertension may carry subclinical kidney disease from the donor to the recipient and, thus, lead to adverse recipient outcomes. We examined eGFR trajectories and all-cause allograft failure in recipients from donors with versus without hypertension, using mixed-linear and Cox regression models stratified by donor age. We studied a US cohort from 1/1/2005 to 6/30/2017; 49 990 recipients of allografts from younger (<50 years old) donors including 597 with donor hypertension and 21 130 recipients of allografts from older (≥50 years old) donors including 1441 with donor hypertension. Donor hypertension was defined as documented predonation use of antihypertensive therapy. Among recipients from younger donors with versus without hypertension, the annual eGFR decline was -1.03 versus -0.53 ml/min/m2 (P = 0.002); 13-year allograft survival was 49.7% vs. 59.0% (adjusted allograft failure hazard ratio [aHR] 1.23; 95% CI 1.05-1.43; P = 0.009). Among recipients from older donors with versus without hypertension, the annual eGFR decline was -0.67 versus -0.66 ml/min/m2 (P = 0.9); 13-year allograft survival was 48.6% versus 52.6% (aHR 1.05; 95% CI 0.94-1.17; P = 0.4). In secondary analyses, our inferences remained similar for risk of death-censored allograft failure and mortality. Hypertension in younger, but not older, living kidney donors is associated with worse recipient outcomes.


Assuntos
Hipertensão , Transplante de Rim , Aloenxertos , Estudos de Coortes , Sobrevivência de Enxerto , Humanos , Rim , Transplante de Rim/efeitos adversos , Doadores Vivos , Pessoa de Meia-Idade , Estudos Retrospectivos , Doadores de Tecidos , Resultado do Tratamento
13.
BMC Nephrol ; 22(1): 26, 2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33435916

RESUMO

BACKGROUND: Post-Transplant erythrocytosis (PTE) has not been studied in large recent cohorts. In this study, we evaluated the incidence, risk factors, and outcome of PTE with current transplant practices using the present World Health Organization criteria to define erythrocytosis. We also tested the hypothesis that the risk of PTE is greater with higher-quality kidneys. METHODS: We utilized the Deceased Donor Study which is an ongoing, multicenter, observational study of deceased donors and their kidney recipients that were transplanted between 2010 and 2013 across 13 centers. Eryrthocytosis is defined by hemoglobin> 16.5 g/dL in men and> 16 g/dL in women. Kidney quality is measured by Kidney Donor Profile Index (KDPI). RESULTS: Of the 1123 recipients qualified to be in this study, PTE was observed at a median of 18 months in 75 (6.6%) recipients. Compared to recipients without PTE, those with PTE were younger [mean 48±11 vs 54±13 years, p < 0.001], more likely to have polycystic kidney disease [17% vs 6%, p < 0.001], have received kidneys from younger donors [36 ±13 vs 41±15 years], and be on RAAS inhibitors [35% vs 22%, p < 0.001]. Recipients with PTE were less likely to have received kidneys from donors with hypertension [16% vs 32%, p = 0.004], diabetes [1% vs 11%, p = 0.008], and cerebrovascular event (24% vs 36%, p = 0.036). Higher KDPI was associated with decreased PTE risk [HR 0.98 (95% CI: 0.97-0.99)]. Over 60 months of follow-up, only 17 (36%) recipients had sustained PTE. There was no association between PTE and graft failure or mortality, CONCLUSIONS: The incidence of PTE was low in our study and PTE resolved in majority of patients. Lower KDPI increases risk of PTE. The underutilization of RAAS inhibitors in PTE patients raises the possibility of under-recognition of this phenomenon and should be explored in future studies.


Assuntos
Transplante de Rim , Policitemia/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Adulto , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Doadores de Tecidos
14.
J Am Soc Nephrol ; 31(1): 175-185, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31852720

RESUMO

BACKGROUND: Early steroid withdrawal (ESW) is associated with acceptable outcomes in kidney transplant (KT) recipients. Recipients with delayed graft function (DGF), however, often have a suboptimal allograft milieu, which may alter the risk/benefit equation for ESW. This may contribute to varying practices across transplant centers. METHODS: Using the Scientific Registry of Transplant Recipients, we studied 110,019 adult deceased-donor KT recipients between 2005 and 2017. We characterized the association of DGF with the use of ESW versus continued steroid maintenance across KT centers, and quantified the association of ESW with acute rejection, graft failure, and mortality using multivariable logistic and Cox regression with DGF-ESW interaction terms. RESULTS: Overall 29.2% of KT recipients underwent ESW. Recipients with DGF had lower odds of ESW (aOR=0.600.670.75). The strength of this association varied across 261 KT centers, with center-specific aOR of <0.5 at 31 (11.9%) and >1.0 at 22 (8.4%) centers. ESW was associated with benefits and harms among recipients with immediate graft function (IGF), but only with harms among recipients with DGF. ESW was associated with increased acute rejection (aOR=1.091.161.23), slightly increased graft failure (aHR=1.011.061.12), but decreased mortality (aHR=0.860.890.93) among recipients with IGF. Among recipients with DGF, ESW was associated with a similar increase in rejection (aOR=1.12; 95% CI, 1.02 to 1.23), a more pronounced increase in graft failure (aHR=1.16; 95% CI, 1.08 to 1.26), and no improvement in mortality (aHR=1.00; 95% CI, 0.94 to 1.07). DGF-ESW interaction was statistically significant for graft failure (P=0.04) and mortality (P=0.003), but not for rejection (P=0.6). CONCLUSIONS: KT centers in the United States use ESW inconsistently in recipients with DGF. Our findings suggest ESW may lead to worse KT outcomes in recipients with DGF.


Assuntos
Função Retardada do Enxerto/epidemiologia , Glucocorticoides/administração & dosagem , Transplante de Rim , Suspensão de Tratamento/estatística & dados numéricos , Adulto , Cadáver , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Doadores de Tecidos
15.
Medicina (Kaunas) ; 57(5)2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-34065914

RESUMO

Since its first detection in 1948, donor-derived cell-free DNA (dd-cfDNA) has been employed for a myriad of indications in various medical specialties. It has had a far-reaching impact in solid organ transplantation, with the most widespread utilization in kidney transplantation for the surveillance and detection of allograft rejection. The purpose of this review is to track the arc of this revolutionary test-from origins to current use-along with examining challenges and future prospects though the lens of transplant nephrology.


Assuntos
Ácidos Nucleicos Livres , Transplante de Rim , Transplantes , Rejeição de Enxerto , Humanos , Doadores de Tecidos
16.
Am J Transplant ; 20(8): 2264-2268, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32185872

RESUMO

In this report, we describe the first kidney retransplantation performed after anti-programmed cell death-1 (PD-1)-related allograft rejection. In 2014, we administered pembrolizumab (anti-PD-1) for ~9 months to a 57-year-old kidney transplant recipient with metastatic cutaneous squamous cell carcinoma (CSCC). The patient experienced both a complete antitumor response and T cell-mediated allograft rejection requiring reinitiation of hemodialysis. Four-and-a-half years after initiating pembrolizumab, the patient remained without evidence of CSCC relapse and received a kidney transplant from a living-unrelated donor. Ten-and-a-half months after kidney retransplantation, the allograft is functioning well and the patient's CSCC remains in remission. This case illustrates the potential for PD-1 blockade to bring about durable immune-mediated tumor control in chronically immunosuppressed patients, and begins to address the feasibility of kidney retransplantation in patients who have previously received immune checkpoint inhibitor therapy for cancer. Results from this and future cases may help elucidate mechanisms of antitumor immunity and allograft tolerance, and inform updates to transplant decision models. Our report also underscores the need for clinical trials testing novel immunotherapy combinations in solid organ transplant recipients designed to uncouple antitumor and anti-allograft immunity.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Cutâneas , Aloenxertos , Pré-Escolar , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/etiologia , Humanos , Rim , Recidiva Local de Neoplasia , Receptor de Morte Celular Programada 1 , Reoperação , Neoplasias Cutâneas/tratamento farmacológico
17.
Am J Transplant ; 20(3): 788-796, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31553823

RESUMO

Successful simultaneous pancreas-kidney transplantation (SPK) improves quality-of-life and prolongs kidney allograft and patient survival in type-1 diabetic (T1DM) patients. However, the use of SPK in type-2 diabetic (T2DM) patients remains limited. We examined a national transplant registry for 35 849 T2DM kidney disease patients who received transplant between 2000 and 2016 and survived the first 3 months with a functioning kidney, and categorized as: deceased-donor kidney transplant alone (DD-KA, 68%), living-donor kidney transplant alone (LD-KA, 30%), or SPK (2%). Among SPK recipients, 6% had pancreas allograft failure within 3 months (SPK,P-) and 94% had a functional pancreas (SPK,P+). Associations of transplant type with kidney allograft failure and death (multivariable-adjusted hazard ratio, 95%LCL aHR95%UCL ), over follow-up through December 2018, were quantified by multivariable inverse probability of treatment weighted survival analyses. SPK recipients had better kidney graft and patient survival than LD-KA or DD-KA recipients. Compared to SPK,P+, DD-KA, or LD-KA recipients had significantly higher risk of kidney allograft failure (DD-KA: aHR 1.53 2.203.17 ; LD-KA: aHR 1.29 1.872.71 ) and death (DD-KA: aHR 2.12 3.255.00 ; LD-KA: aHR 1.54 2.353.59 ). SPK,P- recipients had significantly higher risk of death (aHR 1.68 3.306.50 ). Similar to T1DM, T2DM patients with SPK have a survival benefit compared to those with kidney transplant alone, but this benefit depends upon successful early pancreas function.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Transplante de Rim , Transplante de Pâncreas , Sobrevivência de Enxerto , Humanos , Transplante de Rim/efeitos adversos , Pâncreas
18.
Am J Kidney Dis ; 76(1): 72-81, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32029264

RESUMO

RATIONALE & OBJECTIVE: Intact cognition is generally a prerequisite for navigating through and completing evaluation for kidney transplantation. Despite kidney transplantation being contraindicated for those with severe dementia, screening for more mild forms of cognitive impairment before referral is rare. Candidates may have unrecognized cognitive impairment, which may prolong evaluation, elevate mortality risk, and hinder access to kidney transplantation. We estimated the burden of cognitive impairment and its association with access to kidney transplantation and waitlist mortality. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 3,630 participants (January 2009 to June 2018) with cognitive function measured (by the Modified Mini-Mental State Examination [3MS]) at kidney transplantation evaluation at 1 of 2 transplantation centers. PREDICTORS: Cognitive impairment (3MS score<80). OUTCOMES: Listing, waitlist mortality, and kidney transplantation. ANALYTICAL APPROACH: We estimated the adjusted chance of listing (Cox regression), risk for waitlist mortality (competing-risks regression), and kidney transplantation rate (Poisson regression) by cognitive impairment. Given potential differences in cause of cognitive impairment among those with and without diabetes, we tested whether these associations differed by diabetes status using a Wald test. RESULTS: At evaluation, 6.4% of participants had cognitive impairment, which was independently associated with 25% lower chance of listing (adjusted HR, 0.75; 95% CI, 0.61-0.91); this association did not differ by diabetes status (Pinteraction=0.07). There was a nominal difference by diabetes status for the association between cognitive impairment and kidney transplantation rate (Pinteraction=0.05), while the association between cognitive impairment and waitlist mortality differed by diabetes status kidney transplantation rates (Pinteraction=0.02). Among candidates without diabetes, those with cognitive impairment were at 2.47 (95% CI, 1.31-4.66) times greater risk for waitlist mortality; cognitive impairment was not associated with this outcome among candidates with diabetes. LIMITATIONS: Single measure of cognitive impairment. CONCLUSIONS: Cognitive impairment is associated with a lower chance of being placed on the waitlist, and among patients without diabetes, with increased mortality on the waitlist. Future studies should investigate whether implementation of screening for cognitive impairment improves these outcomes.


Assuntos
Cognição/fisiologia , Disfunção Cognitiva/mortalidade , Diabetes Mellitus/mortalidade , Transplante de Rim/mortalidade , Listas de Espera/mortalidade , Adulto , Idoso , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/cirurgia , Estudos de Coortes , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Estudos Prospectivos , Fatores de Risco
19.
Transfusion ; 60(3): 628-636, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31957889

RESUMO

BACKGROUND: Isohemagglutinins (anti-A and anti-B) mediate hemolytic transfusion reactions, antibody-mediated rejection of solid-organ transplants, and delayed engraftment after stem cell transplant. However, quantification of isohemagglutinins is often labor intensive and operator dependent, limiting availability and interfacility comparisons. We evaluated an automated, solid-phase and agglutination-based antibody titer platform versus manual gel testing. STUDY DESIGN AND METHODS: Plasma samples were obtained from 54 randomly selected patients. Titers were determined by our laboratory's standard assay (manual dilution followed by manual gel testing) and were compared to results obtained on a fully automated blood bank analyzer (Galileo NEO, Immucor). The analyzer determined immunoglobulin G (IgG) antibodies using solid-phase and immunoglobulin M (IgM) antibodies by direct hemagglutination. RESULTS: Isohemagglutinin titers obtained by manual gel versus the automated assay generally (>80%) agreed within one doubling dilution, and always (100%) agreed within two dilutions. Among O samples, the gel titer and the highest titer obtained with the automated assay (either IgG or IgM) were similar in paired, nonparametric analysis (p = 0.06 for anti-A; p = 0.13 for anti-B). Gel titers from group A and group B patients were slightly higher than the highest titer obtained using the automated assay (p = 0.04 for group A; p = 0.009 for group B), although these differences were within the accepted error of measurement. CONCLUSION: Manual and automated methodologies yielded similar isohemagglutinin titers. Separate quantification of IgM and IgG isohemagglutinins via automated titration may yield additional insight into hemolysis, graft survival after ABO-incompatible transplantation, and red blood cell engraftment after ABO-incompatible stem cell transplant.


Assuntos
Hemaglutininas/metabolismo , Sistema ABO de Grupos Sanguíneos/imunologia , Sistema ABO de Grupos Sanguíneos/metabolismo , Incompatibilidade de Grupos Sanguíneos/imunologia , Sobrevivência de Enxerto , Hemaglutininas/imunologia , Humanos , Imunoglobulina G/metabolismo , Imunoglobulina M/metabolismo
20.
Nephrol Dial Transplant ; 35(5): 870-877, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31860087

RESUMO

BACKGROUND: Approximately half of the patients who progress to end-stage kidney disease (ESKD) and undergo dialysis develop difficulties carrying out essential self-care activities, leading to institutionalization and mortality. It is unclear what percentage of kidney transplant (KT) candidates, a group of ESKD patients selected to be healthy enough to withstand transplantation, are functionally independent and whether independence is associated with better access to KT and reduced waitlist mortality. METHODS: We studied a prospective cohort of 3168 ESKD participants (January 2009 to June 2018) who self-reported functional independence in more basic self-care Activities of Daily Living (ADL) (needing help with eating, dressing, walking, grooming, toileting and bathing) and more complex instrumental ADL (IADL) (needing help using a phone, shopping, cooking, housework, washing, using transportation, managing medications and managing money). We estimated adjusted associations between functional independence (separately) and listing (Cox), waitlist mortality (competing risks) and transplant rates (Poisson). RESULTS: At KT evaluation, 92.4% were independent in ADLs, but only 68.5% were independent in IADLs. Functionally independent participants had a higher chance of listing for KT [ADL: adjusted hazard ratio (aHR) = 1.55, 95% confidence interval (CI) 1.30-1.87; IADL: aHR = 1.39, 95% CI 1.26-1.52]. Among KT candidates, ADL independence was associated with lower waitlist mortality risk [adjusted subdistribution HR (aSHR) = 0.66, 95% CI 0.44-0.98] and higher rate of KT [adjusted incidence rate ratio (aIRR) = 1.58, 95% CI 1.12-2.22]; the same was not observed for IADL independence (aSHR = 0.86, 95% CI 0.65-1.12; aIRR = 1.01, 95% CI 0.97-1.19). CONCLUSIONS: Functional independence in more basic self-care ADL was associated with better KT access and lower waitlist mortality. Nephrologists, geriatricians and transplant surgeons should screen KT candidates for ADLs, and identify interventions to promote independence and improve waitlist outcomes.


Assuntos
Atividades Cotidianas , Pessoas com Deficiência/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Falência Renal Crônica/mortalidade , Transplante de Rim/mortalidade , Listas de Espera/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Desempenho Físico Funcional , Prognóstico , Estudos Prospectivos , Autorrelato , Taxa de Sobrevida , Adulto Jovem
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