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1.
Pediatr Transplant ; 28(3): e14743, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38566336

RESUMO

BACKGROUND: There are scant data on the effect of rituximab on EBV DNA levels and prevention of post-transplant lymphoproliferative disorder (PTLD) in pediatric kidney transplant recipients with EBV DNAemia. METHODS: Kidney transplant recipients with EBV DNAemia treated with rituximab to prevent PTLD between 7/1999 and 7/2019 at five pediatric centers were included. Those with confirmed PTLD at the onset of rituximab were excluded. Primary outcomes included percentage change in EBV DNAemia and occurrence of PTLD post rituximab. RESULTS: Twenty-six pediatric kidney transplant recipients were included. Median age at transplant was 4 years (IQR 2.1-10.3). EBV DNA load monitoring by qPCR was performed at 1-3 month intervals. EBV DNAemia onset occurred at a median of 73 days post-transplant (IQR 52-307), followed by DNAemia peak at a median of 268 days (IQR 112-536). Rituximab was administered at a median of 9 days post peak (IQR 0-118). Rituximab regimens varied; median dose 375 mg/m2 (IQR 375-439) weekly for 1-4 doses per course. Following rituximab, EBV DNA load decreased to <10% of baseline at 120 days in 20/26 patients; however, only 30% achieved complete resolution at last follow-up (median 2094 days post-transplant [IQR 1538-3463]). Two (7%) developed PTLD at 915 and 1713 days post rituximab. All recipients had functioning grafts. One death occurred in a child with PTLD following remission due to unrelated reasons. CONCLUSIONS: In the largest pediatric kidney transplant recipient case series with EBV DNAemia given rituximab to prevent PTLD, rituximab achieved a short-term reduction in DNA load; however, recurrent DNAemia is common.


Assuntos
Infecções por Vírus Epstein-Barr , Transplante de Rim , Transtornos Linfoproliferativos , Nefrologia , Humanos , Criança , Pré-Escolar , Rituximab/uso terapêutico , Herpesvirus Humano 4/genética , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/prevenção & controle , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Transplante de Rim/efeitos adversos , DNA Viral , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/prevenção & controle , Transtornos Linfoproliferativos/tratamento farmacológico , Transplantados , Carga Viral
2.
Pediatr Nephrol ; 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38285058

RESUMO

BACKGROUND: Infants and toddlers with kidney failure are susceptible to neurodevelopmental delays due to medical comorbidities and rapid brain development in early childhood. However, research on the neuropsychological development of this patient population has been limited over the past 10 years. METHODS: We performed a retrospective study to evaluate the neurodevelopmental functioning of infants/toddlers with kidney failure who completed the Bayley Scales of Infant and Toddler Development (3rd and 4th Edition) as part of a pretransplant evaluation between 2010 and 2022 (n = 23; Mage = 18 months, SD = 8.53; 16 males) using t-tests, linear model, and Pearson correlations. RESULTS: Mean Bayley scores of participants were below normative means for cognition (M = 86.74, 95% CI = 80.53-92.94, p < 0.001), language (M = 79.20, 95% CI = 73.32-85.08, p < 0.001), and motor (M = 78.00, 95% CI = 70.15-85.85, p < 0.001) domains. After adjusting for prematurity and epilepsy, patients on dialysis had significantly lower cognitive (78.7 vs. 93.8; p = 0.001) and motor scores (67.1 vs. 85.5; p = 0.01) compared to no dialysis. Pretransplant cognitive scores were positively correlated with posttransplant Full-Scale IQ (r(8) = 0.65 p = 0.04), verbal comprehension (r(8) = 0.75 p = 0.02), and fluid reasoning (r(7) = 0.68 p = 0.045). Similarly, pretransplant language scores were positively correlated with posttransplant Full-Scale IQ (r(7) = 0.74 p = 0.03) and verbal comprehension (r(7) = 0.73 p = 0.03). Of the 16 participants who reached age > 5 years during the study period, seven were diagnosed with a neurodevelopmental disorder, including three with autism spectrum disorder. CONCLUSIONS: Infants and toddlers with kidney failure are at risk of developmental delays and later neurodevelopmental disorders. Dialysis is associated with cognitive and motor delays independent of prematurity and epilepsy.

3.
Pediatr Nephrol ; 39(5): 1459-1468, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38082091

RESUMO

BACKGROUND: Coronavirus disease of 2019 (COVID-19) has disproportionately affected adults with kidney disease. Data regarding outcomes among children with kidney disease are limited. The North American Pediatric Renal Trials Collaborative Studies Registry (NAPRTCS) has followed children with chronic kidney disease (CKD) since 1987 at 87 participating centers. This study aimed to evaluate the impact of COVID-19 among participants enrolled in the three arms of the registry: CKD, dialysis, and transplant. METHODS: This was a retrospective cohort study of COVID-19 among participants in the NAPRTCS CKD, dialysis, and transplant registries from 2020 to 2022. Where appropriate, t-tests, chi-square analyses, and univariate logistic regression were used to evaluate the data. RESULTS: The cohort included 1505 NAPRTCS participants with recent data entry; 260 (17%) had documented COVID-19. Infections occurred in all three registry arms, namely, 10% (n = 29) in CKD, 11% (n = 67) in dialysis, and 26% (n = 164) in transplant. The majority of participants (75%) were symptomatic. Hospitalizations occurred in 17% (n = 5) of participants with CKD, 27% (n = 18) maintenance dialysis participants, and 26% (n = 43) of transplant participants. Fourteen percent (n = 4) of CKD participants and 10% (n = 17) of transplant participants developed acute kidney injury (AKI), and a total of eight participants (one CKD, seven transplant) required dialysis initiation. Among transplant participants with moderate to severe illness, 40-43% developed AKI and 29-40% required acute dialysis. There were no reported deaths. CONCLUSIONS: COVID-19 was documented in 17% of active NAPRTCS participants. While there was no documented mortality, the majority of participants were symptomatic, and a quarter required hospitalization.


Assuntos
Injúria Renal Aguda , COVID-19 , Transplante de Rim , Insuficiência Renal Crônica , Criança , Humanos , Adulto Jovem , Estudos Retrospectivos , Diálise Renal , COVID-19/epidemiologia , COVID-19/terapia , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia , Sistema de Registros , América do Norte/epidemiologia
4.
Pediatr Nephrol ; 39(4): 1041-1052, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37632524

RESUMO

In pediatric kidney failure, native kidneys may pose a risk to successful transplant outcomes. The indications and timing of native nephrectomy represent a controversial management decision. A lack of high-quality, outcomes-based data has prevented development of evidence-based guidelines for intervention. In this article, we review the published literature on medical indications for native nephrectomy and current knowledge gaps. In addition, we provide a surgical perspective regarding timing and approach.


Assuntos
Nefropatias , Transplante de Rim , Humanos , Criança , Transplante de Rim/efeitos adversos , Resultado do Tratamento , Nefropatias/cirurgia , Rim , Nefrectomia
5.
Pediatr Nephrol ; 39(2): 631-635, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37725164

RESUMO

BACKGROUND: Early in the history of kidney transplantation, short-term graft survival was low. Yet some have had excellent long-term survival. Herein, we describe characteristics of pediatric recipients with > 40 years of graft survival currently alive with a functioning first graft. METHODS: We reviewed all pediatric (age < 18 years) kidney transplants performed at the University of Minnesota between January 1, 1970, and December 31, 1979 (n = 148), to identify all recipients currently alive with a functioning first graft. Data are presented as medians with interquartile ranges (IQR) and proportions. RESULTS: We identified 10 recipients with > 40-year graft survival (median follow-up: 45.0 years (IQR: 43.1, 48.1)). The median age at transplant was 13.8 years (IQR: 5.1, 16.3). All recipients were white; half were male. Of the 10, 4 had glomerulonephritis, 2 had congenital anomalies of the kidney and the urinary tract, 2 had congenital nephrotic syndrome, 1 had Alport syndrome, and 1 had cystic kidney disease as kidney failure cause. Nine patients received a living-related donor transplant, and 1 patient received a deceased-donor transplant. The median estimated glomerular filtration rate at 20 years post-transplant was 79.9 (IQR: 72.3, 98.4); at 30 years, 67.7 (IQR: 63.2, 91.8); and at 40 years, 80.3 ml/min/1.73 m2 (IQR: 73.7, 86.0). None developed rejection, 5 developed hypertension, 2 developed dyslipidemia, 1 developed diabetes, and 7 patients developed malignancy (4 skin cancer, 2 breast cancer, and 1 post-transplant lymphoproliferative disease). CONCLUSION: Pediatric kidney transplant recipients may achieve > 4 decades of graft survival. Cancer is a common complication warranting vigilant screening.


Assuntos
Transplante de Rim , Adolescente , Criança , Feminino , Humanos , Masculino , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Rim , Transplante de Rim/efeitos adversos , Doadores Vivos , Estudos Retrospectivos , Transplantados , Resultado do Tratamento , Pré-Escolar
6.
Pediatr Transplant ; 28(1): e14631, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37937507

RESUMO

BACKGROUND: The optimal age of kidney transplantation for infants and toddlers with kidney failure is unclear. We aimed to evaluate the patient survival associated with kidney transplantation before 2 years of age versus remaining on the waitlist until ≥2 years. METHOD: We used the Scientific Registry of Transplant Recipients to identify all children added to the deceased-donor waitlist before 2 years of age between 1/1/2000 and 4/30/2020. For each case aged <2 years at transplant, we created a control group comprising all candidates on the waitlist on the case's transplant date. Patient survival was evaluated using sequential Cox regression. Dialysis-free time was defined as graft survival time for cases and the sum of dialysis-free time on the waitlist and graft survival time for controls. RESULTS: We observed similar patient survival for posttransplant periods 0-3 and 4-12 months but higher survival for period >12 months for <2-year decreased-donor recipients (aHR: 0.32; 95% CI: 0.13-0.78; p = .01) compared with controls. Similarly, patient survival was higher for <2-year living-donor recipients for posttransplant period >12 months (aHR: 0.21; 95% CI: 0.06-0.73; p = .01). The 5-year dialysis-free survival was higher for <2-year deceased- (difference: 0.59 years; 95% CI: 0.23-0.93) and living-donor (difference: 1.84 years; 95% CI: 1.31-2.25) recipients. CONCLUSION: Kidney transplantation in children <2 years of age is associated with improved patient survival and reduced dialysis exposure compared with remaining on the waitlist until ≥2 years.


Assuntos
Transplante de Rim , Humanos , Pré-Escolar , Doadores Vivos , Sobrevivência de Enxerto , Diálise Renal , Transplantados , Sistema de Registros
8.
Front Pediatr ; 11: 1098434, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36891229

RESUMO

Human cytomegalovirus (CMV) remains one of the most common opportunistic infections following solid organ transplantation in children. CMV causes morbidity and mortality through direct tissue-invasive disease and indirect immunomodulatory effects. In recent years, several new agents have emerged for the prevention and treatment of CMV disease in solid organ transplant recipients. However, pediatric data remain scarce, and many of the treatments are extrapolated from the adult literature. Controversies exist about the type and duration of prophylactic therapies and the optimal dosing of antiviral agents. This review provides an up-to-date overview of treatment modalities used to prevent and treat CMV disease in solid organ transplant (SOT) recipients.

9.
Pediatr Nephrol ; 38(7): 2209-2219, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36508051

RESUMO

BACKGROUND: Understanding disparities in pediatric kidney transplants is important to provide equitable care. We compared transplant outcomes between English-speaking (ES) and interpreter-needing (IN) pediatric kidney transplant recipients. METHODS: Through retrospective review, primary kidney transplant recipients, 0-21 years transplanted between 2005 and 2019, were divided into ES and IN cohorts. Continuous and categorical variables were compared using Wilcoxon rank-sum, Welch two-sample t-test, and chi-squared analyses. Patient survival, graft survival, and rejection-free survival were evaluated using Kaplan-Meier methods and Cox regression. Days hospitalized were evaluated using negative binomial regression. RESULTS: Our sample included 211 ES and 37 IN transplant recipients. Compared with the ES, the IN cohort was older at transplant (14.56 vs. 11.03 years; p < 0.01), had more time between kidney failure and transplant (0.9 vs. 0.3 years; p < 0.01), and more often received deceased over living donor transplants (78.4% vs. 30.4%; p < 0.01). Multivariate Cox proportional-hazard models evaluating adjusted 5-year patient survival demonstrated decreased 5-year post-transplant survival in the IN cohort (aHR = 10.10, 95% CI: 1.5, 66.8; p = 0.02). We did not identify differences in 5-year death-censored graft survival (aHR = 0.57; 95% CI: 0.14, 2.4; p = 0.4) nor rejection-free survival (aHR = 0.8; 95% CI: 0.4, 1.5; p = 0.5). We found significantly fewer hospitalization events in the IN cohort during the first year post-transplant (aRR: 0.62; 95% CI: 0.4, 0.9; p = 0.01) but no difference 5-year post-transplant. The IN cohort had more missed outpatient appointments (10.4% vs. 2.8%; p = 0.03) and undetectable serum immunosuppressant levels (mean: 3.8% vs. 1.3%; p = 0.02) 5 years post-transplant. CONCLUSIONS: Pediatric kidney transplant recipients requiring interpreter services for healthcare delivery demonstrate fewer post-transplant interactions with their healthcare team (fewer hospitalizations and more no-show visits) and lower 5-year patient survival compared with recipients not requiring interpreters. A higher resolution version of the Graphical abstract is available as Supplementary information.


Assuntos
Transplante de Rim , Humanos , Criança , Transplante de Rim/métodos , Rejeição de Enxerto , Doadores Vivos , Modelos de Riscos Proporcionais , Sobrevivência de Enxerto , Estudos Retrospectivos , Barreiras de Comunicação , Resultado do Tratamento
10.
Pediatr Transplant ; 27(1): e14372, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35938684

RESUMO

BACKGROUND: Pediatric data on risk factors and the clinical course of BK DNAemia are limited. We aimed to determine the effects of BK DNAemia on transplant outcomes and delineate the safety and efficacy of various treatment approaches. METHODS: This retrospective-cohort study included 161 transplants (age ≤ 21 years) performed at a single center between 1/1/2012 and 1/1/2020. We used Cox proportional models to evaluate the effects of BK DNAemia on patient survival (PS), graft survival (GS), and acute rejection (AR), using BK as a time-dependent covariate. We also assessed the effects of pharmacological intervention on BK DNAemia duration using intervention as a time-dependent covariate. RESULTS: BK-free survival was 69.1% at 1-year and 54.6% at 3-year posttransplant. After multivariate adjustment, BK DNAemia was associated with young age at transplant (aHR, age 5-<12 vs. ≥12 (years): 2.5 (1.4-4.5); p = .001) and steroid-based immunosuppression (IS) (aHR: 2.2 [1.1-4.5]; p = .03). We found no effect of DNAemia on AR (aHR: 1.25; p = .5), PS (aHR: 2.85; p = .22), and GS (aHR: 0.56; p = .41). Of 70 patients with DNAemia, 22 (31.4%) received no treatment, 20 (28.6%) received IS reduction alone, and 28 patients (40%) received treatment with at least one pharmacological agent (leflunomide, IVIG, ciprofloxacin, cidofovir). Sixty-three patients (90%) cleared DNAemia with median time to resolution of 2.4 months (IQR:1.4-5.6). We found no significant effect of BK-directed pharmacological treatment on time to resolution (aHR: 0.64;p = .13). BK-directed agents were well tolerated. CONCLUSIONS: BK DNAemia is associated with a young age at transplant and steroid-based maintenance IS. We found no effect of BK DNAemia on AR, GS, and PS.


Assuntos
Vírus BK , Transplante de Rim , Infecções por Polyomavirus , Infecções Tumorais por Vírus , Humanos , Criança , Adulto Jovem , Adulto , Pré-Escolar , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Estudos de Coortes , Terapia de Imunossupressão , Transplantados , Esteroides/uso terapêutico , Infecções por Polyomavirus/etiologia , Infecções Tumorais por Vírus/etiologia
11.
Front Pediatr ; 10: 929504, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35795334

RESUMO

Posttransplant anemia (PTA) is a common complication of pediatric kidney transplantation, with a prevalence ranging from 22 to 85%. PTA is categorized as early (within 6 months posttransplant) and late (>6 months posttransplant). Early PTA is typically associated with surgical blood losses and iron deficiency. Late PTA primarily results from graft dysfunction; however, iron deficiency, drug toxicity, and posttransplant inflammation also play a role. PTA is more severe compared with the anemia in glomerular-filtration-rate matched patients with native chronic kidney disease. Treatment of PTA is directed toward the underlying cause. Erythropoiesis stimulating agents (ESA) are effective; however, their use is limited in the transplant setting. Timely diagnosis and treatment of PTA are vital to prevent long-term adverse outcomes in pediatric transplant recipients.

12.
Transplantation ; 106(3): 575-583, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33654002

RESUMO

BACKGROUND: Kidneys donated after circulatory death (DCD) are increasingly being used for transplantation in adults to alleviate organ shortage. Pediatric data on survival benefits of DCD transplantation compared with remaining on the waitlist for a kidney donated after brain death (DBD) offer are lacking. METHODS: We used Scientific Registry of Transplant Recipients to identify 285 pediatric (<18 y) DCD kidney transplants performed between 1987 and 2017. Propensity score matching was used to create a comparison group of 1132 DBD transplants. We used sequential Cox analysis to evaluate survival benefit of DCD transplantation versus remaining on the waitlist and Cox regression to evaluate patient and graft survival. RESULTS: DCD transplantation was associated with a higher incidence of delayed graft function (adjusted odds ratio: 3.0; P < 0.001). The risks of graft failure (adjusted hazard ratio [aHR], 0.89; P = 0.46) and death (aHR, 1.2; P = 0.67) were similar between DCD and DBD recipients. We found a significant survival benefit of DCD transplantation compared with remaining on the waitlist awaiting a DBD kidney (aHR, 0.44; P = 0.03). CONCLUSIONS: Despite a higher incidence of delayed graft function, long-term patient and graft survival are similar between pediatric DCD and DBD kidney transplant recipients. DCD transplantation in children is associated with a survival benefit, despite pediatric priority for organ allocation, compared with remaining on the waitlist.


Assuntos
Transplante de Rim , Obtenção de Tecidos e Órgãos , Adulto , Morte Encefálica , Criança , Morte , Sobrevivência de Enxerto , Humanos , Rim , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Doadores de Tecidos , Listas de Espera
13.
Pediatr Transplant ; 26(2): e14189, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34786800

RESUMO

BACKGROUND: Corticosteroids have been an integral part of maintenance immunosuppression for pediatric kidney transplantation. However, prolonged steroid therapy is associated with significant toxicities resulting in several SW/avoidance strategies in recent years. METHOD/OBJECTIVE: This comprehensive review aims to discuss steroid-related toxicities and the safety, efficacy, and benefit of steroid avoidance/withdrawal immunosuppression in pediatric kidney transplant recipients. RESULTS: Initial studies of SW/avoidance conducted in the setting of CSA and AZA showed an increased incidence of AR but no increase in graft loss or mortality with SW/avoidance maintenance immunosuppression. Studies performed under modern immunosuppression (induction therapy, Tac, and MMF) show no significant increase in AR or graft loss with SW/avoidance immunosuppression. Furthermore, SW/avoidance immunosuppression is associated with significant improvement in growth, BMI, BP control, and lipid profile in pediatric kidney transplant recipients. Despite these data, SW/avoidance remains controversial, and only 40% of pediatric kidney transplant recipients in the United States are currently on SW/avoidance maintenance immunosuppression. CONCLUSION: SW/avoidance maintenance immunosuppression is safe and associated with fewer side effects compared with steroid-inclusive maintenance immunosuppression in pediatric kidney transplant recipients.


Assuntos
Corticosteroides/administração & dosagem , Imunossupressores/uso terapêutico , Transplante de Rim , Criança , Humanos , Suspensão de Tratamento
14.
Clin Nephrol ; 97(3): 157-166, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34642018

RESUMO

BACKGROUND: Registry data from Europe has shown an increase in age at end-stage kidney disease for patients with Alport syndrome in recent years. Whether a similar delay in transplant age has occurred in the United States for Alport patients across all racial/ethnic groups is unknown. MATERIALS AND METHODS: We used data from the Scientific Registry of Transplant Recipients (SRTR) to identify 3,794 Alport patients transplanted between 12/1987 and 12/2017. We divided the study period into five equal eras to assess temporal trends in age at transplant, graft survival, and patient survival across racial groups using linear regression and Cox regression models. RESULTS: The mean age at transplant for Blacks (28.3 years; difference (Black vs. White): 8.9 years; p < 0.0001) and Hispanics (28.7 years; difference (Hispanics vs. White): 8.7 years; p < 0.0001) was significantly younger compared with that of Whites. We observed a temporal increase in age at transplant for Whites but not for Blacks and Hispanics (p-value for interaction: 0.001). Black recipients were at a higher risk of graft loss (aHR: 1.78; 95% CI: 1.47, 2.15; p < 0.0001) and death (aHR: 1.73; 95% CI: 1.11, 2.69; p = 0.02) compared with White recipients. We observed significant improvements in graft survival with each successive era (p < 0.01). Temporal trends in graft survival (interaction p = 0.46) were not modified by race. CONCLUSION: We found racial disparities in age at transplant and long-term graft survival for patients with Alport syndrome in the United States. The age at transplant increased over time for Whites but not Black and Hispanic patients.


Assuntos
Transplante de Rim , Nefrite Hereditária , População Negra , Sobrevivência de Enxerto , Humanos , Transplante de Rim/efeitos adversos , Nefrite Hereditária/diagnóstico , Nefrite Hereditária/cirurgia , Estudos Retrospectivos , Estados Unidos/epidemiologia , População Branca
15.
Curr Opin Pediatr ; 34(2): 197-202, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34923562

RESUMO

PURPOSE OF REVIEW: The purpose of this review is to highlight recent studies that have emerged on the topic of ANCA-associated vasculitis with some historical context. The review also discusses how the adult data is relevant to pediatric patients. RECENT FINDINGS: Pediatric studies on AAV are lacking. Therapies targeted to the inflammatory cascade specifically implicated in AAV, such as MPO inhibitors and complement mediators, are emerging. The PEXIVAS study recently called into question the routine use of plasma exchange (PLEX) in severe AAV, with no difference in ESKD or mortality found between patients who did or did not receive PLEX. Longer maintenance duration of nearly 48 months is preferred as compared with shorter duration in patients who are not on dialysis because of higher relapse rates in children with AAV. SUMMARY: Current treatment in AAV includes corticosteroids, rituximab, and cyclophosphamide for induction. Maintenance therapy commonly consists of azathioprine or rituximab. Plasma exchange (PLEX) is no longer recommended for induction therapy for AAV but some experts still consider this as an option for patients who are not responding to therapy or have severe disease at presentation. However, emerging novel therapies may be on the horizon.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Adulto , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/terapia , Azatioprina , Criança , Humanos , Imunossupressores/uso terapêutico , Rim , Troca Plasmática , Rituximab/uso terapêutico
17.
Pediatr Transplant ; 25(7): e14077, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34216190

RESUMO

Advances in immunosuppression have improved graft survival in pediatric kidney transplant recipients; however, treatment-related toxicities need to be balanced against the possibility of graft rejection. Several immunosuppressive agents are available for use in transplant recipients; however, the optimal combinations of agents remain unclear, resulting in variations in institutional protocols. Lymphocyte-depleting antibodies, specifically ATG, are the most common induction agent used for pediatric kidney transplantation in the US. Basiliximab may be used for induction in immunologically low-risk children; however, pediatric data are scarce. CNIs and antiproliferative agents (mostly Tac and mycophenolate in recent years) constitute the backbone of maintenance immunosuppression. Steroid-avoidance maintenance regimens remain controversial. Belatacept and mTOR inhibitors are used in children under specific circumstances such as non-adherence or CNI toxicity. This article reviews the indications, mechanism of action, efficacy, dosing, and side effect profiles of various immunosuppressive agents available for pediatric kidney transplantation.


Assuntos
Rejeição de Enxerto/prevenção & controle , Terapia de Imunossupressão/tendências , Imunossupressores/uso terapêutico , Transplante de Rim , Criança , Humanos
18.
Transpl Int ; 34(6): 1019-1031, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33735480

RESUMO

The increasing global prevalence of SARS-CoV-2 and the resulting COVID-19 disease pandemic pose significant concerns for clinical management of solid organ transplant recipients (SOTR). Wearable devices that can measure physiologic changes in biometrics including heart rate, heart rate variability, body temperature, respiratory, activity (such as steps taken per day) and sleep patterns, and blood oxygen saturation show utility for the early detection of infection before clinical presentation of symptoms. Recent algorithms developed using preliminary wearable datasets show that SARS-CoV-2 is detectable before clinical symptoms in >80% of adults. Early detection of SARS-CoV-2, influenza, and other pathogens in SOTR, and their household members, could facilitate early interventions such as self-isolation and early clinical management of relevant infection(s). Ongoing studies testing the utility of wearable devices such as smartwatches for early detection of SARS-CoV-2 and other infections in the general population are reviewed here, along with the practical challenges to implementing these processes at scale in pediatric and adult SOTR, and their household members. The resources and logistics, including transplant-specific analyses pipelines to account for confounders such as polypharmacy and comorbidities, required in studies of pediatric and adult SOTR for the robust early detection of SARS-CoV-2, and other infections are also reviewed.


Assuntos
COVID-19 , Transplante de Órgãos , Dispositivos Eletrônicos Vestíveis , Adulto , Criança , Humanos , Pandemias , SARS-CoV-2
19.
Pediatr Nephrol ; 36(8): 2349-2360, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33693990

RESUMO

BACKGROUND: Eculizumab is approved for the treatment of atypical hemolytic uremic syndrome (aHUS). Its use off-label is frequently reported. The aim of this study was to describe the broader use and outcomes of a cohort of pediatric patients exposed to eculizumab. METHODS: A retrospective, cohort analysis was performed on the clinical and biomarker characteristics of eculizumab-exposed patients < 25 years of age seen across 21 centers of the Pediatric Nephrology Research Consortium. Patients were included if they received at least one dose of eculizumab between 2008 and 2015. Traditional summary statistics were applied to demographic and clinical data. RESULTS: A total of 152 patients were identified, mean age 9.1 (+/-6.8) years. Eculizumab was used "off-label" in 44% of cases. The most common diagnoses were aHUS (47.4%), Shiga toxin-producing Escherichia coli HUS (12%), unspecified thrombotic microangiopathies (9%), and glomerulonephritis (9%). Genetic testing was available for 60% of patients; 20% had gene variants. Dosing regimens were variable. Kidney outcomes tended to vary according to diagnosis. Infectious adverse events were the most common adverse event (33.5%). No cases of meningitis were reported. Nine patients died of noninfectious causes while on therapy. CONCLUSIONS: This multi-center retrospective cohort analysis indicates that a significant number of children and young adults are being exposed to C5 blockade for off-label indications. Dosing schedules were highly variable, limiting outcome conclusions. Attributable adverse events appeared to be low. Cohort mortality (6.6%) was not insignificant. Prospective studies in homogenous disease cohorts are needed to support the role of C5 blockade in kidney outcomes.


Assuntos
Nefrologia , Adolescente , Anticorpos Monoclonais Humanizados/efeitos adversos , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Síndrome Hemolítico-Urêmica Atípica/genética , Criança , Humanos , Estudos Prospectivos , Estudos Retrospectivos
20.
Am J Transplant ; 21(3): 1160-1170, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32594613

RESUMO

Pediatric kidney transplant outcomes associated with expanded-criteria donors (ECD) and high Kidney Donor Profile Index (KDPI) kidneys are unknown. We reviewed the Scientific Registry of Transplant Recipients data from 1987-2017 to identify 96 ECD and 92 > 85 KDPI kidney recipients (<18 years). Using propensity scores, we created comparison groups of 375 non-ECD and 357 ≤ 85 KDPI recipients for comparisons with ECD and > 85 KDPI transplants, respectively. We used Cox regression for patient/graft survival and sequential Cox approach for survival benefit of ECD and > 85 KDPI transplantationvs remaining on the waitlist. After adjustment, ECD recipients were at significantly increased risk of graft failure (adjusted hazard ratio [aHR] = 1.6; P = .001) but not of mortality (aHR = 1.33; P = .15) compared with non-ECD recipients. We observed no survival benefit of ECD transplants vs remaining on the waitlist (aHR = 1.05; P = .83). We found no significant difference in graft failure (aHR = 1.27; P = .12) and mortality (aHR = 1.41; P = .13) risks between > 85 KDPI and ≤ 85 KDPI recipients. However, > 85 KDPI transplants were associated with a survival benefit vs remaining on the waitlist (aHR = 0.41; P = .01). ECD transplantation in children is associated with a high graft loss risk and no survival benefit, whereas > 85 KDPI transplantation is associated with a survival benefit for children vs remaining on the waitlist.


Assuntos
Transplante de Rim , Criança , Sobrevivência de Enxerto , Humanos , Rim , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Doadores de Tecidos , Transplantados , Estados Unidos/epidemiologia
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