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1.
Pediatr Transplant ; 28(4): e14786, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38766983

RESUMO

BACKGROUND: Adult kidney transplant recipients (KTRs) fully vaccinated against COVID-19 have substantial morbidity and mortality related to SARS-CoV-2 infection compared with the general population. However, little is known regarding the safety and efficacy of the COVID-19 vaccination series in pediatric KTRs. METHODS: A multicenter, retrospective observational study was performed across nine pediatric transplantation centers. Eligible KTRs fully vaccinated against COVID-19 were enrolled and data were collected pertaining to SARS-CoV-2 infection incidence and severity, graft outcomes and post-vaccination safety profile, as well as overall patient survival. RESULTS: A total of 247 patients were included in this investigation with a median age at transplantation of 11 years (IQR 5-15). SARS-CoV-2 infection was observed in 30/110 (27.27%) of fully vaccinated patients, tested post-transplant, within the defined follow-up period. Of these patients, 6/30 (18.18%) required hospitalization and 3/30 (12.12%) required reduction in immunosuppression, with no reported deaths. De novo donor-specific antibodies (DSAs) were found in 8/86 (9.30%) of DSA-tested patients with two experiencing rejection and subsequent graft loss. The overall incidence of rejection and graft loss among the total cohort was 11/247 (4.45%) and 6/247 (3.64%), respectively. A 100% patient survival was observed. CONCLUSIONS: Observationally, infectious outcomes of SARS-CoV-2 in fully vaccinated pediatric KTRs are excellent, with a low incidence of infection requiring hospitalization and no associated deaths. Though de novo DSAs were observed, there was minimal graft rejection and graft loss reported in the total cohort.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Transplante de Rim , Humanos , Criança , Masculino , Estudos Retrospectivos , Feminino , COVID-19/prevenção & controle , COVID-19/epidemiologia , Adolescente , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/administração & dosagem , Pré-Escolar , SARS-CoV-2/imunologia , Rejeição de Enxerto/prevenção & controle , Transplantados , Incidência , Vacinação , Sobrevivência de Enxerto
2.
Pediatr Nephrol ; 39(7): 2087-2090, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38261065

RESUMO

Neuroblastoma is a common pediatric tumor arising from the post-ganglionic sympathetic nervous system and is associated with hypertension in 25% of cases. We describe an unusual case of labile, multi-drug resistant hypertension associated with chemotherapy administration for neuroblastoma and provide potential management strategies in this scenario. We report the case of a 4-year-old female with a history of headaches who presented with hypertensive emergency and evidence of end-organ damage, including posterior reversible encephalopathy syndrome, acute cerebral infarct, concentric left ventricular hypertrophy, and growth failure secondary to a large, abdominal catecholamine-secreting neuroblastoma, which compressed the kidney vasculature and inferior vena cava. She was classified as intermediate risk according to Children's Oncology Group criteria and underwent chemotherapy, complicated by labile hypertension, followed by surgical resection. Vigilance in monitoring and treatment of hypertension is recommended during chemotherapy for neuroblastoma due to the potential catecholamine release in the setting of tumor lysis.


Assuntos
Catecolaminas , Hipertensão , Neuroblastoma , Humanos , Neuroblastoma/complicações , Feminino , Catecolaminas/metabolismo , Pré-Escolar , Hipertensão/etiologia , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/administração & dosagem
3.
Pediatr Nephrol ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38976042

RESUMO

IMPORTANCE: Pediatric patients with complex medical problems benefit from pediatric sub-specialty care; however, a significant proportion of children live greater than 80 mi. away from pediatric sub-specialty care. OBJECTIVE: To identify current knowledge gaps and outline concrete next steps to make progress on issues that have persistently challenged the pediatric nephrology workforce. EVIDENCE REVIEW: Workforce Summit 2.0 employed the round table format and methodology for consensus building using adapted Delphi principles. Content domains were identified via input from the ASPN Workforce Committee, the ASPN's 2023 Strategic Plan survey, the ASPN's Pediatric Nephrology Division Directors survey, and ongoing feedback from ASPN members. Working groups met prior to the Summit to conduct an organized literature review and establish key questions to be addressed. The Summit was held in-person in November 2023. During the Summit, work groups presented their preliminary findings, and the at-large group developed the key action statements and future directions. FINDINGS: A holistic appraisal of the effort required to cover inpatient and outpatient sub-specialty care will help define faculty effort and time distribution. Most pediatric nephrologists practice in academic settings, so work beyond clinical care including education, research, advocacy, and administrative/service tasks may form a substantial amount of a faculty member's time and effort. An academic relative value unit (RVU) may assist in creating a more inclusive assessment of their contributions to their academic practice. Pediatric sub-specialties, such as nephrology, contribute to the clinical mission and care of their institutions beyond their direct billable RVUs. Advocacy throughout the field of pediatrics is necessary in order for reimbursement of pediatric sub-specialist care to accurately reflect the time and effort required to address complex care needs. Flexible, individualized training pathways may improve recruitment into sub-specialty fields such as nephrology. CONCLUSIONS AND RELEVANCE: The workforce crisis facing the pediatric nephrology field is echoed throughout many pediatric sub-specialties. Efforts to improve recruitment, retention, and reimbursement are necessary to improve the care delivered to pediatric patients.

4.
Pediatr Nephrol ; 38(5): 1653-1665, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36251074

RESUMO

BACKGROUND: Acute kidney injury (AKI) is common in lupus nephritis (LN) and a risk factor for development of chronic kidney disease. In adults with LN, AKI severity correlates with the incidence of kidney failure and patient survival. Data on AKI outcomes in children with LN, particularly those requiring kidney replacement therapy (KRT), are limited. METHODS: A multicenter, retrospective cohort study was performed in children diagnosed between 2010 and 2019 with LN and AKI stage 3 treated with dialysis (AKI stage 3D). Descriptive statistics were used to characterize demographics, clinical data, and kidney biopsy findings; treatment data for LN were not included. Logistic regression was used to examine the association of these variables with kidney failure. RESULTS: Fifty-nine patients (mean age 14.3 years, 84.7% female) were identified. The most common KRT indications were fluid overload (86.4%) and elevated blood urea nitrogen/creatinine (74.6%). Mean follow-up duration was 3.9 ± 2.9 years. AKI recovery without progression to kidney failure occurred in 37.3% of patients. AKI recovery with later progression to kidney failure occurred in 25.4% of patients, and there was no kidney recovery from AKI in 35.6% of patients. Older age, severe (> 50%) tubular atrophy and interstitial fibrosis, and National Institutes of Health (NIH) chronicity index score > 4 on kidney biopsy were associated with kidney failure. CONCLUSIONS: Children with LN and AKI stage 3D have a high long-term risk of kidney failure. Severe tubular atrophy and interstitial fibrosis at the time of AKI, but not AKI duration, are predictive of kidney disease progression. A higher resolution version of the Graphical abstract is available as Supplementary information.


Assuntos
Injúria Renal Aguda , Artrite Juvenil , Nefrite Lúpica , Nefrologia , Reumatologia , Adulto , Criança , Humanos , Feminino , Adolescente , Masculino , Nefrite Lúpica/complicações , Nefrite Lúpica/terapia , Nefrite Lúpica/diagnóstico , Estudos de Coortes , Estudos Retrospectivos , Artrite Juvenil/complicações , Diálise Renal , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Fibrose , Atrofia/complicações
5.
Pediatr Transplant ; 25(3): e13921, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33280223

RESUMO

Dapsone has been utilized for the prevention of Pneumocystis jirovecii pneumonia in immunosuppressed patients including pediatric kidney transplant recipients, in whom trimethoprim-sulfamethoxazole (TMP-SMX) is contraindicated. Dapsone adverse effects include methemoglobinemia, but there are no reports of the burden and impact of methemoglobinemia in pediatric kidney recipients that are taking dapsone for PJP prophylaxis. We conducted a retrospective chart review of all pediatric kidney recipients who had received dapsone at any time posttransplant. The indication, duration, and adverse effects of dapsone therapy were assessed. In addition, methemoglobin levels were assessed, and summary statistics performed. Data demonstrated that more than half of the patients on dapsone were not screened for methemoglobinemia. Of those screened, there was a significantly higher acquired-methemoglobinemia (77%) than previously reported in the literature. We also demonstrate significantly more anemia in patients on dapsone. Methemoglobinemia did not affect patient or graft survival and resolved with cessation of dapsone. We conclude that pediatric kidney recipients often develop methemoglobinemia and / or anemia on dapsone. We recommend if pediatric transplant recipients are prescribed dapsone, routine testing for methemoglobinemia and anemia should be done.


Assuntos
Anti-Infecciosos/efeitos adversos , Dapsona/efeitos adversos , Transplante de Rim , Metemoglobinemia/induzido quimicamente , Complicações Pós-Operatórias/induzido quimicamente , Anti-Infecciosos/uso terapêutico , Criança , Dapsona/uso terapêutico , Feminino , Humanos , Masculino , Pneumonia por Pneumocystis/prevenção & controle , Estudos Retrospectivos
6.
Pediatr Transplant ; 25(5): e13952, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33326667

RESUMO

BACKGROUND: No consensus exists on the optimal timing for native nephrectomy in pediatric kidney transplant recipients. Data comparing outcomes between recipients undergoing pretransplant nephrectomy (staged nephrectomy with subsequent transplant) and those undergoing nephrectomy simultaneously with the transplant are lacking. METHOD: We studied 32 pediatric kidney transplant recipients who underwent native nephrectomy at a single center from 01/01/2011 to 12/31/2016. We divided recipients into two groups based on the nephrectomy timing (simultaneous nephrectomy/transplant and staged nephrectomy). We used Wilcoxon rank-sum test, Fisher's exact test, and Kaplan-Meier methods to compare outcomes. RESULTS: Of 32 recipients, 20 underwent simultaneous and 12 underwent staged nephrectomy. Simultaneous recipients were younger (median (years): 2.0 vs 7.0; P = .049). Staged recipients were more likely to have proteinuria/hypoalbuminemia, whereas simultaneous recipients were more likely to have hydronephrosis/vesicoureteral reflux/urinary infections as nephrectomy indications (P = .06). Median prenephrectomy albumin for patients with nephrotic syndrome was significantly lower in staged recipients (median g/dL: 1.9 vs 3.8; P = .02). Total number of hospital days (including both procedures) was higher for staged recipients compared with simultaneous (one procedure) recipients (median (days): 17.0 vs 11.5; P = .05). We observed no difference in 5-year graft survival between the groups (95.0% vs 91.7%, P = .73). Patient survival was 100% in both groups over a median follow-up of 44.2 months. Surgical complications were similar between the groups. CONCLUSION: Staged and simultaneous native nephrectomy in pediatric kidney transplant recipients are associated with comparable outcomes.


Assuntos
Transplante de Rim/métodos , Nefrectomia/métodos , Adolescente , Fatores Etários , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Estimativa de Kaplan-Meier , Masculino , Avaliação de Resultados em Cuidados de Saúde , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Análise de Sobrevida , Fatores de Tempo
7.
Pediatr Transplant ; 25(6): e13974, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33512738

RESUMO

INTRODUCTION: There are no guidelines regarding management of failed pediatric renal transplants. MATERIALS & METHODS: We performed a first of its kind multicenter study assessing prevalence of transplant nephrectomy, patient characteristics, and outcomes in pediatric renal transplant recipients with graft failure from January 1, 2006, to December 31, 2016. RESULTS: Fourteen centers contributed data on 186 pediatric recipients with failed transplants. The 76 recipients that underwent transplant nephrectomy were not significantly different from the 110 without nephrectomy in donor or recipient demographics. Fifty-three percent of graft nephrectomies were within a year of transplant. Graft tenderness prompted transplant nephrectomy in 91% (P < .001). Patients that underwent nephrectomy were more likely to have a prior diagnosis of rejection within 3 months (43% vs 29%; P = .04). Nephrectomy of allografts did not affect time to re-listing, donor source at re-transplant but significantly decreased time to (P = .009) and incidence (P = .0002) of complete cessation of immunosuppression post-graft failure. Following transplant nephrectomy, recipients were significantly more likely to have rejection after re-transplant (18% vs 7%; P = .03) and multiple rejections in first year after re-transplant (7% vs 1%; P = .03). CONCLUSIONS: Practices pertaining to failed renal allografts are inconsistent-40% of failed pediatric renal allografts underwent nephrectomy. Graft tenderness frequently prompted transplant nephrectomy. There is no apparent benefit to graft nephrectomy related to sensitization; but timing / frequency of immunosuppression withdrawal is significantly different with slightly increased risk for rejection following re-transplant.


Assuntos
Rejeição de Enxerto/epidemiologia , Transplante de Rim , Nefrectomia/métodos , Adolescente , Aloenxertos , Criança , Feminino , Humanos , Masculino , Reoperação , Estados Unidos/epidemiologia
8.
Pediatr Transplant ; 24(5): e13717, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32447837

RESUMO

BACKGROUND: Little data exist on re-hospitalization rates in pediatric kidney recipients (KTx) particularly with the evolution of transplant immunosuppression. METHODS: In a single-center, retrospective study of pediatric KTx between 2006 and 2016, we assessed re-hospitalization after KTx admission, stratified by whether the re-admit was early (<30 days post-KTx discharge) or late (>30 days), and compared two different immunosuppression eras (one with and one without steroids). RESULTS: Of 197 KTx, 156 (79%) patients were re-hospitalized in 1st year, 85 (56%) within 30 days of discharge (total 490 1st year re-hospitalizations). Younger age was associated with early and late re-hospitalizations. African American race was associated with early re-hospitalizations. Of the 123 and 74 discharged on steroid-avoidance (maintenance immunosuppression included MMF in 95%; FK in 50%; CSA in 50%) and steroid-inclusive (AZA in 66%; MMF in 34%; FK in 30%; CSA in 70%), re-hospitalization rates, timing post-transplant, length, and number were not significantly different (P .38; .1; .56; .11). Admission diagnoses analysis demonstrated that steroid-avoidance recipients had anemia/leucopenia/thrombocytopenia, significantly more often, as one of their admission diagnoses (16% vs 4%; P < .001) and had a rejection diagnosis significantly less often (6% vs 18%; P < .001). Infection diagnoses were not statistically different between groups. Re-hospitalization, early or late, did not predict worse graft/ patient survival but predicted further hospitalizations. CONCLUSIONS: Re-hospitalization is common after pediatric transplant discharge and predicts further hospitalization regardless of discharge on or off steroids.


Assuntos
Rejeição de Enxerto/epidemiologia , Transplante de Rim , Readmissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Adolescente , Negro ou Afro-Americano , Fatores Etários , Criança , Pré-Escolar , Feminino , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Humanos , Imunossupressores/uso terapêutico , Lactente , Masculino , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/terapia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
10.
Pediatr Transplant ; 28(1): e14667, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38054539
11.
Pediatr Transplant ; 23(8): e13582, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31515921

RESUMO

Effective treatment modalities for diarrhea in solid organ transplant recipients are lacking. We evaluated the effect of oral IgG on clinical course of diarrhea in pediatric kidney transplant recipients. We retrospectively studied all pediatric kidney transplant recipients who required hospitalization for diarrhea between January 1, 2015, and December 31, 2017. We divided the recipients into two groups based on whether they had received oral IgG to treat diarrhea. Sixteen pediatric kidney transplant recipients required hospitalization for diarrhea over 3 years. Median age at admission was 9.25 years (IQR:12.54). Fifty-six percent of recipients were male, and 81% were white. Four patients received oral IgG for prolonged diarrhea. Oral IgG recipients had longer diarrheal duration before admission (median (days) 14.5 vs1; P .02), a trend for greater weight loss at admission (median (kilogram) 1.4 vs 0.2; P .3), and a trend for higher acute kidney injury (>75% reduction in glomerular filtration rate: 100% vs 42%; P .36). Diarrhea resolved completely in 3 (75%) oral IgG recipients and 7 (58%) non-oral IgG patients by discharge (P .99). One oral IgG recipient showed partial improvement but also had biopsy evidence of mycophenolate-induced colitis. All patients tolerated oral IgG well. No patients required re-hospitalization within 30 days of discharge. Oral IgG may be used safely and effectively to treat prolonged diarrhea in pediatric kidney transplant recipients. A larger, randomized, prospective study is needed to further assess the efficacy of oral IgG in the treatment of diarrhea.


Assuntos
Diarreia/tratamento farmacológico , Imunoglobulina G/administração & dosagem , Fatores Imunológicos/administração & dosagem , Transplante de Rim , Complicações Pós-Operatórias/tratamento farmacológico , Administração Oral , Criança , Feminino , Humanos , Masculino , Estudos Retrospectivos
12.
Pediatr Res ; 81(1-2): 259-264, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27732587

RESUMO

Successful renal transplantation is the optimal treatment for chronic kidney failure, but this was not always so for children. Beginning with the first kidney transplants in the 1950s, children experienced poorer patient and graft survival rates than adult patients. But over the last 6 decades, an improved understanding of the immune system which has steered pediatric multi-center clinical/pharmacokinetic and mechanistic studies that have sculpted our immunosuppression with markedly better patient and graft survivals. In addition, uniquely pediatric issues related to growth, development, neurocognitive maturation, increased complications from primary viral infections, and comorbid congenital/inherited disorders, are now diagnosed and effectively managed in these children. Refined pretransplant preparation (vaccinations for preventable diseases, attention to cognitive delays, effective dialysis and nutrition) improved donor selection, and more potent immunosuppression have all contributed to enhanced outcomes. Similarly, improvements in pediatric surgical techniques, postoperative care and better antiviral prophylaxis have all shortened hospitalizations and reduced morbidity. Today pediatric kidney transplant outcomes are markedly improved and younger children today experience better long-term graft survival than adults! While difficult problems remain, we have made tremendous progress and anticipate even more advances in the future of pediatric kidney transplantation.


Assuntos
Falência Renal Crônica/cirurgia , Transplante de Rim/história , Transplante de Rim/métodos , Nefrologia/história , Criança , Pré-Escolar , Sobrevivência de Enxerto , História do Século XX , História do Século XXI , Humanos , Terapia de Imunossupressão , Imunossupressores/uso terapêutico , Lactente , Falência Renal Crônica/história , Transplante de Rim/efeitos adversos , Taxa de Sobrevida , Resultado do Tratamento
13.
Clin Transplant ; 31(11)2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28915342

RESUMO

Epstein-Barr virus (EBV) poses a significant threat to patient and graft survival post-transplant. We hypothesized that recipients who shed EBV at transplant had less immunologic control of the virus and hence were more likely to have active EBV infection and disease post-transplant. To test this hypothesis, we conducted a 5-year prospective study in primary solid organ transplant recipients. We measured EBV DNA in oral washes and blood samples by quantitative PCR before transplant and periodically thereafter for up to 4 years. Pre-transplant samples were available from 98 subjects. EBV DNA was detected pre-transplant in 32 of 95 (34%) and 5 of 93 subjects (5%) in oral wash and blood, respectively. Recipients with and without detectable pre-transplant EBV DNA were not significantly different demographically and had no significant difference in patient and graft survival (P = .6 for both comparisons) or post-transplant EBV viremia-free survival (P = .8). There were no cases of EBV-related disease or post-transplant lymphoproliferative disorder (PTLD) in any of the patients with detectable EBV DNA pre-transplant. In conclusion, detectable EBV DNA pre-transplant was not associated with differences in patient/graft survival, post-transplant EBV viremia, or EBV-related diseases including PTLD.


Assuntos
DNA Viral/genética , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4/genética , Transtornos Linfoproliferativos/diagnóstico , Transplante de Órgãos , Viremia/diagnóstico , Adolescente , Adulto , Idoso , Infecções por Vírus Epstein-Barr/virologia , Feminino , Seguimentos , Humanos , Transtornos Linfoproliferativos/epidemiologia , Transtornos Linfoproliferativos/virologia , Masculino , Pessoa de Meia-Idade , Minnesota/epidemiologia , Prognóstico , Estudos Prospectivos , Fatores de Risco , Carga Viral , Viremia/epidemiologia , Viremia/virologia , Adulto Jovem
14.
Pediatr Transplant ; 21(5)2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28452096

RESUMO

Pediatric patients requiring kidney transplant after hematopoietic cell transplant receive multiple courses of immunosuppression placing them at risk for infection. To elucidate potential risk factors for infection, we compared the immunosuppressive regimens and infectious complications of pediatric kidney transplant recipients at a single institution who had previously undergone hematopoietic cell transplant from different donors to similar patients reported in the literature. Among the initial four post-hematopoietic cell transplant kidney transplant patients reviewed, viremia episodes were universal, including BK virus, Epstein-Barr virus, and human herpesvirus-6, with one death from presumed BK virus encephalitis. No viremia was reported in five similar cases in the literature. Risk factors for increased infection include use of lymphodepleting serotherapy in HCT conditioning, multiple HCTs, limited immune reconstitution time between transplants, increased pre-KTx viral burden, and use of T-cell-depleting versus -suppressive induction immunosuppression for KTx. These findings suggest that pediatric post-HCT KTx recipients are at increased risk for viral infections, likely benefitting from thorough pre-KTx evaluation of immune reconstitution and preferential use of non-T-cell-depleting induction therapy for KTx. We applied these recommendations to one subsequent post-HCT patient requiring KTx at our institution with excellent outcomes one year post-KTx.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Imunossupressores/efeitos adversos , Transplante de Rim , Complicações Pós-Operatórias/etiologia , Viremia/etiologia , Adolescente , Criança , Pré-Escolar , Feminino , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/uso terapêutico , Masculino , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Fatores de Risco , Viremia/diagnóstico , Viremia/epidemiologia
15.
Pediatr Transplant ; 21(7)2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28869324

RESUMO

MMF is commonly prescribed following kidney transplantation, yet its use is complicated by leukopenia. Understanding the genetics mediating this risk will help clinicians administer MMF safely. We evaluated 284 patients under 21 years of age for incidence and time course of MMF-related leukopenia and performed a candidate gene association study comparing the frequency of 26 SNPs between cases with MMF-related leukopenia and controls. We matched cases by induction, steroid duration, race, center, and age. We also evaluated the impact of induction and SNPs on time to leukopenia in all cases. Sixty-eight (24%) patients had MMF-related leukopenia, of which 59 consented for genotyping and 38 were matched with controls. Among matched pairs, no SNPs were associated with leukopenia. With non-depleting induction, UGT2B7-900A>G (rs7438135) was associated with increased risk of MMF-related leukopenia (P = .038). Time to leukopenia did not differ between patients by induction agent, but 2 SNPs (rs2228075, rs2278294) in IMPDH1 were associated with increased time to leukopenia. MMF-related leukopenia is common after transplantation. UGT2B7 may influence leukopenia risk especially in patients without lymphocyte-depleting induction. IMPDH1 may influence time course of leukopenia after transplant.


Assuntos
Predisposição Genética para Doença , Imunossupressores/efeitos adversos , Transplante de Rim , Leucopenia/induzido quimicamente , Ácido Micofenólico/efeitos adversos , Polimorfismo de Nucleotídeo Único , Complicações Pós-Operatórias/induzido quimicamente , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Estudos de Associação Genética , Marcadores Genéticos , Humanos , Incidência , Lactente , Leucopenia/epidemiologia , Leucopenia/genética , Modelos Logísticos , Masculino , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/genética , Estudos Retrospectivos , Adulto Jovem
16.
Nephrol Dial Transplant ; 29(1): 209-18, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24414376

RESUMO

BACKGROUND: Given the nephrotoxicity of calcineurin inhibitors (CNIs), we asked whether their addition improved living related donor (LRD) human leukocyte antigen (HLA) identical kidney transplant recipient outcomes. METHODS: We performed a comprehensive literature review and a single-center study comparing patient survival (PS) and graft survival (GS) of LRD HLA-identical kidney transplants for three different immunosuppression eras: Era 1 (up to 1984): anti-lymphocyte globulin (ALG) induction and maintenance immunosuppression with prednisone and azathioprine (AZA) (n = 114); Era 2a (1984-99): CNI added; evolution from ALG to thymoglobulin; AZA to mycophenolate (n = 262). Era 2b (1999-2011): rapid discontinuation of prednisone (thymoglobulin induction, CNI and mycophenolate) in recipients having first or second transplant and not previously on prednisone (n = 77). RESULTS: Demographics differed by era: recipient (P < 0.0001) and donor age (P < 0.0001) increased and the proportion of Caucasian donors (P = 0.02) and recipients (P = 0.003) decreased with each advancing era. There was no significant difference in PS (P = 0.6); cause of death (P = 0.5); death-censored GS (P = 0.8) or graft loss from acute rejection by era. Graft loss from chronic allograft nephropathy (P = 0.02) and hypertension (P = 0.005) were greater in the CNI eras. There were no significant differences in the 1/creatinine slopes between eras for the first (P = 0.6), second (P = 0.9) or >2 years post-transplant (P = 0.4). Literature review revealed no clear benefits for CNI in these human leukocyte antigen (HLA) identical LRD graft recipients. CONCLUSIONS: This study confirmed that there are no benefits of CNIs for HLA-identical LRD recipients. Moreover, we did find evidence of potential harm. Thus, monotherapy or early discontinuation of CNI should be given consideration in these patients.


Assuntos
Inibidores de Calcineurina , Rejeição de Enxerto/prevenção & controle , Antígenos HLA , Transplante de Rim , Doadores Vivos , Adolescente , Adulto , Soro Antilinfocitário/imunologia , Azatioprina/uso terapêutico , Criança , Creatinina/metabolismo , Ciclosporina/uso terapêutico , Feminino , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Tacrolimo/uso terapêutico , Adulto Jovem
17.
Pediatr Blood Cancer ; 61(2): 366-8, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24038944

RESUMO

Neutropenic fever is a common complication of myelosuppressive therapy in pediatric oncology patients. Piperacillin-tazobactam (PIP/TAZO) is a broad spectrum antibiotic used for empiric treatment of neutropenic fever. We describe four cases of suspected PIP/TAZO induced nephrotoxicity occurring in children with pediatric malignancies admitted to the hospital and treated for fever ± neutropenia. All patients exhibited acute renal injury shortly after PIP/TAZO administration with one of these cases having biopsy evidence of acute interstitial nephritis. These findings are suggestive of PIP/TAZO induced nephrotoxicity in pediatric oncology patients with fever ± neutropenia and that PIP/TAZO should be used judiciously in this population.


Assuntos
Antibacterianos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Nefropatias/diagnóstico , Neoplasias/complicações , Neutropenia/tratamento farmacológico , Ácido Penicilânico/análogos & derivados , Adolescente , Feminino , Humanos , Nefropatias/induzido quimicamente , Masculino , Neoplasias/tratamento farmacológico , Neutropenia/induzido quimicamente , Ácido Penicilânico/efeitos adversos , Piperacilina/efeitos adversos , Combinação Piperacilina e Tazobactam , Prognóstico
18.
J Clin Virol ; 172: 105678, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38688164

RESUMO

BACKGROUND: Valganciclovir (valG), a cytomegalovirus (CMV) prophylactic agent, has dose-limiting side effects. The tolerability and effectiveness of valacyclovir (valA) as CMV prophylaxis is unknown. METHODS: We conducted a randomized, open-label, single-center trial of valA versus valG for all posttransplant CMV prophylaxis in adult and pediatric kidney recipients. Participants were randomly assigned to receive valA or valG. Primary endpoints were the incidence of CMV viremia and side-effect related drug reduction with secondary assessment of incidence of EBV viremia. RESULTS: Of the 137 sequential kidney transplant recipients enrolled, 26 % were positive and negative for CMV antibody in donor and recipient respectively. The incidence of CMV viremia (4 of 71 [6 %]; 8 of 67 [12 %] P = 0.23), time to viremia (P = 0.16) and area under CMV viral load time curve (P = 0.19) were not significantly different. ValG participants were significantly more likely to require side-effect related dose reduction (15/71 [21 %] versus 1/66 [2 %] P = 0.0003). Leukopenia was the most common reason for valG dose reduction and granulocyte-colony stimulating factor was utilized for leukopenia recovery more frequently (25 % in valG vs 5 % in valA: P = 0.0007). Incidence of EBV viremia was not significantly different. CONCLUSIONS: ValA has significantly less dose-limiting side effects than valG. In our study population, a significant increase in CMV viremia was not observed, in adults and children after kidney transplant, compared to valG. TRIAL REGISTRATION NUMBER: NCT01329185.


Assuntos
Antivirais , Infecções por Citomegalovirus , Ganciclovir , Transplante de Rim , Transplantados , Valaciclovir , Valganciclovir , Humanos , Valaciclovir/uso terapêutico , Infecções por Citomegalovirus/prevenção & controle , Valganciclovir/uso terapêutico , Valganciclovir/administração & dosagem , Transplante de Rim/efeitos adversos , Antivirais/uso terapêutico , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Masculino , Feminino , Adulto , Criança , Pessoa de Meia-Idade , Adolescente , Ganciclovir/análogos & derivados , Ganciclovir/uso terapêutico , Ganciclovir/administração & dosagem , Ganciclovir/efeitos adversos , Viremia/prevenção & controle , Carga Viral , Adulto Jovem , Valina/análogos & derivados , Valina/uso terapêutico , Valina/administração & dosagem , Citomegalovirus/imunologia , Citomegalovirus/efeitos dos fármacos , Pré-Escolar , Aciclovir/uso terapêutico , Aciclovir/análogos & derivados , Aciclovir/administração & dosagem , Aciclovir/efeitos adversos , Idoso , Resultado do Tratamento , Incidência
19.
medRxiv ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38978683

RESUMO

We investigated the risks of post-acute and chronic adverse kidney outcomes of SARS-CoV-2 infection in the pediatric population via a retrospective cohort study using data from the RECOVER program. We included 1,864,637 children and adolescents under 21 from 19 children's hospitals and health institutions in the US with at least six months of follow-up time between March 2020 and May 2023. We divided the patients into three strata: patients with pre-existing chronic kidney disease (CKD), patients with acute kidney injury (AKI) during the acute phase (within 28 days) of SARS-CoV-2 infection, and patients without pre-existing CKD or AKI. We defined a set of adverse kidney outcomes for each stratum and examined the outcomes within the post-acute and chronic phases after SARS-CoV-2 infection. In each stratum, compared with the non-infected group, patients with COVID-19 had a higher risk of adverse kidney outcomes. For patients without pre-existing CKD, there were increased risks of CKD stage 2+ (HR 1.20; 95% CI: 1.13-1.28) and CKD stage 3+ (HR 1.35; 95% CI: 1.15-1.59) during the post-acute phase (28 days to 365 days) after SARS-CoV-2 infection. Within the post-acute phase of SARS-CoV-2 infection, children and adolescents with pre-existing CKD and those who experienced AKI were at increased risk of progression to a composite outcome defined by at least 50% decline in estimated glomerular filtration rate (eGFR), eGFR <15 mL/min/1.73m 2 , End Stage Kidney Disease diagnosis, dialysis, or transplant. Lay abstract: This study examined the impact of COVID-19 on kidney health in children and adolescents under 21 years old in the United States. Using data from the RECOVER program, we analyzed the health records of 1,864,637 young individuals from 19 hospitals and health institutions between March 2020 and May 2023. The study focused on three groups: those with pre-existing chronic kidney disease (CKD), those who experienced acute kidney injury (AKI) during the initial COVID-19 infection, and those without any prior kidney issues. The results showed that children and adolescents who had COVID-19 were at a higher risk of developing serious kidney problems later on, even if they had no previous kidney conditions. This research highlights the long-term effects of COVID-19 on kidney health in young people and underscores the importance of monitoring kidney function in pediatric COVID-19 patients.

20.
Pediatr Transplant ; 17(1): E9-15, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23171066

RESUMO

BKV has emerged as a significant pathogen in the field of transplantation, predominantly causing BKV nephropathy in renal transplant recipients and hemorrhagic cystitis in HSCT recipients. However, case reports describe more diverse complications, and we too present three unusual cases of BKV infections in pediatric renal transplant recipients. First, we describe a case of biopsy-proven renal damage secondary to BKV prior to the onset of viremia, demonstrating that BKV nephropathy can occur without preceding viremia. We also present two renal transplant recipients with persistent BK viruria, one with BKV-associated hemorrhagic cystitis and the other with microscopic hematuria. Therefore, we conclude that BKV manifestations may be more diverse than previously thought and suggest clinical utility in urine BKV qPCR testing in specific transplant recipients.


Assuntos
Vírus BK/isolamento & purificação , Transplante de Rim , Infecções por Polyomavirus/diagnóstico , Insuficiência Renal/complicações , Adolescente , Biópsia , Rejeição de Enxerto , Hematúria/metabolismo , Humanos , Imunossupressores/uso terapêutico , Masculino , Reação em Cadeia da Polimerase , Infecções por Polyomavirus/complicações , Insuficiência Renal/terapia , Insuficiência Renal/virologia , Ultrassonografia , Bexiga Urinária/diagnóstico por imagem , Viremia
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