Clinical outcome of tacrolimus as maintenance immunosuppressive drug in pediatric heart transplantation

O Tacrolimus é uma potente droga imunossupressora introduzida no transplante cardíaco no início da década de 90. Pacientes com rejeição refratária ou intolerância à ciclosporina podem responder à terapia de resgate com o tacrolimus. Os objetivos deste estudo foram: avaliar a evolução clínica das crianças submetidas ao transplante cardíaco que necessitaram da conversão de ciclosporina para tacrolimus por rejeição refratária, tardia ou efeitos adversos de difícil controle; avaliar a incidência de rejeição após a conversão para o tacrolimus e comparar a sobrevida dos pacientes em uso de tacrolimus e ciclosporina. Realizou-se estudo coorte, observacional, prospectivo, em 28 crianças submetidas ao transplante cardíaco no Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo e que foram submetidas à conversão da ciclosporina ao tacrolimus, no período de julho de 1999 a dezembro de 2009. Avaliou-se a incidência de episódios de rejeição e a sobrevida após a conversão. Realizou-se, também, a comparação entre os pacientes em uso de tacrolimus e os pacientes que permaneceram em uso de ciclosporina submetidos ao transplante cardíaco no mesmo período. A idade média no momento do transplante foi de 5,3 anos, e no momento da conversão de 8,2 anos. As causas de conversão foram efeitos adversos em 50% dos pacientes, rejeição tardia em 32% e rejeição refratária em 18%. O tempo médio de conversão e seguimento foram 36 meses e 74 meses, respectivamente. Observou-se resolução completa dos episódios de rejeição refratária e melhora dos efeitos adversos em todos os pacientes. A taxa de incidência (x100) de episódios de rejeição antes da conversão foi de 7,98 e após a conversão foi de 2,11 (p=0,0001). A taxa de episódios de infecção antes da conversão foi de 5,89 e após a conversão 4,18 (p=0,023). Pela análise das complicações pré e pós-conversão ao tacrolimus, não se evidenciou diferença estatisticamente significativa em relação a incidência de tumor, insuficiência renal, hipertensão arterial sistêmica, dislipidemia, litíase biliar, diabetes melito, anemia, alterações neurológicas, hirsutismo e hiperplasia gengival. Houve maior prevalência da doença vascular do enxerto após conversão para tacrolimus (p=0,004). Ao se comparar os pacientes com tacrolimus e os com ciclosporina, identificou-se diminuição significativa na taxa de incidência de episódios de rejeição (p=0,001), e na taxa de incidência de episódios de infecção (p=0,002), nos pacientes em uso de tacrolimus. Os pacientes convertidos ao tacrolimus apresentaram menor incidência de complicações neurológicas, hirsutismo e hiperplasia gengival, porém maior prevalência de anemia. Em relação à sobrevida, observou-se uma mortalidade de 25% nos pacientes em uso de tacrolimus, após um período médio de conversão de sessenta meses. Três óbitos foram secundários à rejeição, dos quais apenas um, no primeiro ano de transplante. Evidenciou-se menor sobrevida nos pacientes em uso de ciclosporina. O estudo clínico das crianças submetidas ao transplante cardíaco e que necessitaram de conversão do esquema de imunossupressão permitiu concluir que o tacrolimus foi eficaz como terapia de resgate para rejeição refratária e constitui opção terapêutica como droga imunossupressora de manutenção na faixa etária pediátricaTacrolimus is a potent calcineurin inhibitor that was introduced in heart transplantation therapy in the early 1990s. Organ transplant recipients with refractory rejection or intolerance to conventional immunosuppressant may respond to rescue therapy with tacrolimus. The aim of this study was to evaluate the clinical outcome of children undergoing heart transplantation who required conversion from a cyclosporine to a tacrolimus-based immunosuppressive regimen due to refractory rejection, late rejection or cyclosporine intolerance. We performed a prospective observational cohort study in 28 children who underwent cardiac transplantation at the Heart Institute (InCor) University of São Paulo Medical School and who required conversion from July 1999 to December 2009. The clinical outcome of the patients was evaluated after tacrolimus conversion. We also compared the patients on tacrolimus to the patients who remained on cyclosporine, and who had undergone heart transplantation during the same period. The mean age at the time of transplantation was 5.3 years and 8.2 years at the time of conversion. The causes of conversion were adverse side effects in 50% of patients, late rejection in 32% and refractory rejection in 18%. The mean time from heart transplant to conversion was 36 months and the mean follow-up period was 74 months. We observed complete resolution of refractory rejection episodes and adverse side effects in all patients. The incidence rate (x100) of rejection episodes before and after conversion was 7.98 and 2.11, respectively (p = <0.0001). The rate of infectious episodes before conversion was 5.89 and after conversion was 4.18 (p = 0.023). There was no statistically significant difference in relation to tumor, renal failure requiring dialysis, systemic arterial hypertension, dyslipidemia, gallstones, diabetes mellitus, anemia, neurological complications, hirsutism and gingival hyperplasia after conversion. A significant incidence of cardiac allograft vasculopathy after conversion to tacrolimus was found (p = 0.004). When comparing patients on tacrolimus to patients on cyclosporine, there was a significant decrease in the incidence of rejection (p = 0.001), and infectious episodes (p = 0.002) in patients using tacrolimus. Patients converted to tacrolimus when compared to patients on cyclosporine had lower neurological complications, hirsutism and gingival hyperplasia, but higher prevalence of anemia. There was a 25% mortality rate in patients using tacrolimus after a mean period of 60 months after conversion. Three deaths were secondary to rejection, and only one in the first year after transplant. Patients using tacrolimus showed greater survival rate when compared to patients taking cyclosporine. The clinical outcome of children undergoing heart transplantation and who required conversion of immunosuppressive regimen allowed us to conclude that tacrolimus is effective as rescue therapy for refractory rejection and is a therapeutic option in pediatric patient

Acute Kidney Injury in Neonates: From Urine Output to New Biomarkers

In the past 10 years, great effort has been made to define and classify a common syndrome previously known as acute renal failure and now renamed “acute kidney injury (AKI).” Initially suggested and validated in adult populations, AKI classification was adapted to the pediatric population and recently has been modified for the neonatal population. Several studies have been performed in adults and older children using this consensus definition, leading to improvement in the knowledge of AKI incidence and epidemiology. In spite of these advances, the peculiar renal pathophysiology of critically ill newborn patients makes it difficult to interpret urine output (UO) and serum creatinine (SCr) levels in these patients to diagnose AKI. Also, new urine biomarkers have emerged as a possible alternative to diagnose early AKI in the neonatal population. In this review, we describe recent advances in neonatal AKI epidemiology, discuss difficulties in diagnosing AKI in newborns, and show recent advances in new AKI biomarkers and possible long-term consequences after AKI episode

Analysis of Surgical Mortality for Congenital Heart Defects Using RACHS-1 Risk Score in a Brazilian Single Center

ABSTRACT Introduction: Risk Adjustment for Congenital Heart Surgery 1 (RACHS-1) score is a simple model that can be easily applied and has been widely used for mortality comparison among pediatric cardiovascular services. It is based on the categorization of several surgical palliative or corrective procedures, which have similar mortality in the treatment of congenital heart disease. Objective: To analyze the in-hospital mortality in pediatric patients (<18 years) submitted to cardiac surgery for congenital heart disease based on RACHS-1 score, during a 12-year period. Methods: A retrospective date analysis was performed from January 2003 to December 2014. The survey was divided in two periods of six years long each, to check for any improvement in the results. We evaluated the numbers of procedures performed, complexity of surgery and hospital mortality. Results: Three thousand and two hundred and one surgeries were performed. Of these, 3071 were able to be classified according to the score RACHS-1. Among the patients, 51.7% were male and 47.5% were younger than one year of age. The most common RACHS-1 category was 3 (35.5%). The mortality was 1.8%, 5.5%, 14.9%, 32.5% and 68.6% for category 1, 2, 3, 4 and 6, respectively. There was a significant increase in the number of surgeries (48%) and a significant reduction in the mortality in the last period analysed (13.3% in period I and 10.4% in period II; P=0.014). Conclusion: RACHS-1 score was a useful score for mortality risk in our service, although we are aware that other factors have an impact on the total mortality