RESUMO
In this review, we identify important challenges facing physicians responsible for renal and cardiac transplantation in children based on a review of the contemporary medical literature. Regarding pediatric renal transplantation, we discuss the challenge of antibody-mediated rejection, focusing on both acute and chronic antibody-mediated rejection. We review new diagnostic approaches to antibody-mediated rejection, such as panel-reactive antibodies, donor-specific cross-matching, antibody assays, risk assessment and diagnosis of antibody-mediated rejection, the pathology of antibody-mediated rejection, the issue of ABO incompatibility in renal transplantation, new therapies for antibody-mediated rejection, inhibiting of residual antibodies, the suppression or depletion of B-cells, genetic approaches to treating acute antibody-mediated rejection, and identifying future translational research directions in kidney transplantation in children. Regarding pediatric cardiac transplantation, we discuss the mechanisms of cardiac transplant rejection, including the role of endomyocardial biopsy in detecting graft rejection and the role of biomarkers in detecting cardiac graft rejection, including biomarkers of inflammation, cardiomyocyte injury, or stress. We review cardiac allograft vasculopathy. We also address the role of genetic analyses, including genome-wide association studies, gene expression profiling using entities such as AlloMap®, and adenosine triphosphate release as a measure of immune function using the Cylex® ImmuKnow™ cell function assay. Finally, we identify future translational research directions in heart transplantation in children.
Assuntos
Rejeição de Enxerto , Transplante de Coração/efeitos adversos , Transplante de Rim/efeitos adversos , Pesquisa Translacional Biomédica , Anticorpos/imunologia , Biomarcadores/sangue , Criança , Perfilação da Expressão Gênica/métodos , Glomerulosclerose Segmentar e Focal/patologia , Rejeição de Enxerto/genética , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Rejeição de Enxerto/terapia , Teste de Histocompatibilidade , Humanos , Medição de Risco , Tolerância ao TransplanteRESUMO
OBJECTIVES: To distinguish between cystatin C (CysC) and creatinine (Cr) as markers of estimated glomerular filtration rate (eGFR) in preterm infants and to correlate eGFR with total kidney volume (TKV) as a surrogate of nephron mass. STUDY DESIGN: Sixty preterm (<37 weeks' gestational age [GA]) and 40 term infants were enrolled at birth. Serum Cr and CysC levels were assessed during the first week of life. Renal ultrasounds were performed to assess kidney dimensions with calculation of the TKV as a surrogate of nephron mass. Six equations derived from reference inulin, iohexol, and iothalamate clearance studies were used to calculate eGFR. Multiple regression analysis was applied to assess the relative impact of neonatal measures on eGFR, including TKV, GA, and mean arterial pressure (MAP). RESULTS: Renal lengths correlated with GA and were within the reference values for intrauterine measurements. Estimation equations for glomerular filtration rate (GFR) based on Cr, CysC, and combined CysC + Cr demonstrated that Cr-based equations consistently underestimated GFR, whereas CysC and combined equations were more consistent with referenced inulin clearance studies. Term infants demonstrated significantly better eGFR than preterm infants. TKV, GA, and MAP correlated positively with eGFR, although only MAP and GA remained significant when adjusted for other covariates. CONCLUSIONS: Primary determinants of eGFR in preterm infants are GA and MAP. The CysC level is a superior biomarker to serum Cr in the assessment of GFR in premature infants.
Assuntos
Creatinina/sangue , Cistatina C/sangue , Taxa de Filtração Glomerular , Recém-Nascido Prematuro/fisiologia , Rim/anatomia & histologia , Injúria Renal Aguda/sangue , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/fisiopatologia , Biomarcadores/sangue , Estudos Transversais , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro/sangue , Rim/diagnóstico por imagem , Rim/fisiopatologia , Modelos Lineares , Masculino , Análise Multivariada , Tamanho do Órgão , Valores de Referência , UltrassonografiaRESUMO
In this review, we identify important challenges facing physicians responsible for renal and cardiac transplantation in children based on a review of the contemporary medical literature. Regarding pediatric renal transplantation, we discuss the challenge of antibody-mediated rejection, focusing on both acute and chronic antibody-mediated rejection. We review new diagnostic approaches to antibody-mediated rejection, such as panel-reactive antibodies, donor-specific cross-matching, antibody assays, risk assessment and diagnosis of antibody-mediated rejection, the pathology of antibody-mediated rejection, the issue of ABO incompatibility in renal transplantation, new therapies for antibody-mediated rejection, inhibiting of residual antibodies, the suppression or depletion of B-cells, genetic approaches to treating acute antibody-mediated rejection, and identifying future translational research directions in kidney transplantation in children. Regarding pediatric cardiac transplantation, we discuss the mechanisms of cardiac transplant rejection, including the role of endomyocardial biopsy in detecting graft rejection and the role of biomarkers in detecting cardiac graft rejection, including biomarkers of inflammation, cardiomyocyte injury, or stress. We review cardiac allograft vasculopathy. We also address the role of genetic analyses, including genome-wide association studies, gene expression profiling using entities such as AlloMap®, and adenosine triphosphate release as a measure of immune function using the Cylex® ImmuKnow™ cell function assay. Finally, we identify future translational research directions in heart transplantation in children.
Assuntos
Criança , Humanos , Rejeição de Enxerto , Transplante de Coração/efeitos adversos , Transplante de Rim/efeitos adversos , Pesquisa Translacional Biomédica , Anticorpos/imunologia , Biomarcadores/sangue , Perfilação da Expressão Gênica/métodos , Glomerulosclerose Segmentar e Focal/patologia , Rejeição de Enxerto/genética , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Rejeição de Enxerto/terapia , Teste de Histocompatibilidade , Medição de Risco , Tolerância ao TransplanteRESUMO
BACKGROUND: This study describes the incidence, clinical and demographic characteristics, and spectrum of chronic kidney disease (CKD) in youths with perinatal HIV-1 infection. METHODS: Retrospective analysis between May 1993 and December 2006 of subjects with renal disease followed in the Pediatric AIDS Clinical Trials Group 219/219C multicenter study examining the long-term consequences of perinatal HIV infection. Diagnosis confirmation was made utilizing a questionnaire mailed to research sites. Participants with CKD of other etiology than HIV were excluded. Outcome measures were biopsy-diagnosed CKD and, in the absence of biopsy, HIV-associated nephropathy (HIVAN) using established clinical criteria. RESULTS: Questionnaires on 191 out of 2,102 participants identified 27 cases of CKD: 14 biopsy-diagnosed and 6 clinical cases of HIVAN, and 7 biopsy-diagnosed cases of immune complex-mediated kidney disease (lupus-like nephritis, 3; IgA nephropathy, 2; membranous nephropathy, 2). Incidence rates for CKD associated with HIV in pre-highly active antiretroviral therapy (HAART) (1993-1997) and HAART (1998-2002, 2003-2006) eras were 0.43, 2.84, and 2.79 events per 1,000 person years respectively. In multivariate analysis, black race and viral load ≥100,000 copies/mL (rate ratios 3.28 and 5.05, p ≤ 0.02) were associated with CKD. CONCLUSIONS: A variety of immune complex-mediated glomerulonephritides and HIVAN occurs in this population. Black race and uncontrolled viral replication are risk factors for CKD associated with HIV.
Assuntos
Nefropatia Associada a AIDS/epidemiologia , Glomerulonefrite/epidemiologia , Infecções por HIV/epidemiologia , HIV-1/patogenicidade , Nefropatia Associada a AIDS/diagnóstico , Nefropatia Associada a AIDS/imunologia , Nefropatia Associada a AIDS/virologia , Adolescente , Negro ou Afro-Americano/estatística & dados numéricos , Fatores Etários , Biópsia , Contagem de Linfócito CD4 , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Doença Crônica , Feminino , Glomerulonefrite/diagnóstico , Glomerulonefrite/imunologia , Glomerulonefrite/virologia , Infecções por HIV/diagnóstico , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/crescimento & desenvolvimento , Humanos , Incidência , Lactente , Recém-Nascido , Modelos Lineares , Masculino , Estudos Multicêntricos como Assunto , Análise Multivariada , Porto Rico/epidemiologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Inquéritos e Questionários , Fatores de Tempo , Estados Unidos/epidemiologia , Carga Viral , Replicação ViralRESUMO
OBJECTIVE: To perform a retrospective analysis of the long-term outcome of infants with end-stage kidney disease (ESKD) treated at our center during the past 25 years. STUDY DESIGN: The total cohort (n = 52) was divided into era 1 (1983-1995; n = 23) and era 2 (1996-2008; n = 29). Dialysis morbidity, transplantation, and long-term survival rates were assessed and compared between the 2 eras. RESULTS: Average age at initiation of dialysis was 4.4 +/- 5.3 months (range, 0.5-18 months), with 96% begun on peritoneal dialysis. The predominant diagnoses were dysplasia/obstructive uropathy and autosomal recessive polycystic kidney disease. The overall survival rate is 46%, with current age of survivors ranging from 1.5 to 25 years. Mortality rates in the 2 eras were not significantly different. The predominant mortality occurred within the first year. Twenty-four patients received an initial renal transplant at 2.6 +/- 1.7 years of age. Six patients (25%) required a second renal allograft. Increased risk for mortality included African-American ethnicity, oligoanuria, autosomal recessive polycystic kidney disease, and co-morbid diagnoses. CONCLUSIONS: Long-term survival is possible in infants with ESKD, although mortality and morbidity remain high. Technical innovations are needed to accommodate smaller infants undergoing dialysis. Early initiation of dialysis treatment is preferable because prognostic indicators remain poorly defined.
Assuntos
Falência Renal Crônica/mortalidade , Falência Renal Crônica/terapia , Transplante de Fígado/estatística & dados numéricos , Diálise Renal , Anuria/epidemiologia , População Negra , Pré-Escolar , Estudos de Coortes , Comorbidade , Deficiências do Desenvolvimento/epidemiologia , Feminino , Florida/epidemiologia , Gastrostomia , Humanos , Lactente , Recém-Nascido , Masculino , Oligúria/epidemiologia , Peritonite/epidemiologia , Doenças Renais Policísticas/epidemiologia , Estudos Retrospectivos , Análise de Sobrevida , Obstrução Ureteral/epidemiologiaRESUMO
OBJECTIVE: To assess the prevalence of abnormal vitamin D status in children and adolescents with chronic kidney disease (CKD). STUDY DESIGN: This was an outpatient cross-sectional, retrospective study of 258 patients, mean age 12.3 +/- 5.2 years, with an average estimated glomerular filtration rate (eGFR) of 106 +/- 51 mL/min/1.73 m2 (range, 0 to 220 mL/min/1.73 m2). Serum 25-hydroxy-vitamin D [25(OH)D], calcium, phosphorus, and parathyroid hormone levels, as well as selected anthropometric variables, were analyzed. RESULTS: Reduced 25(OH)D concentrations (< 30 ng/mL) were found in 60% of the patients. In 28%, the concentration was < 20 ng/mL, indicating vitamin D deficiency. Patients with more advanced CKD were more likely to have vitamin D deficiency compared with those with incipient CKD or normal GFR (42% vs 26%; P = .03) and displayed more prominent hyperparathyroidism. Suboptimal vitamin D status was similar in males and females, but was significantly more prevalent in older (P < .01), non-Caucasian (P < .01), and overweight (P = .02) patients. Patients with early-stage CKD (eGFR > 60 mL/min/1.73 m2) and with vitamin D deficiency were significantly shorter than their counterparts with 25(OH)D levels > 20 ng/mL (P = .02). CONCLUSIONS: Vitamin D insufficiency and deficiency are very prevalent in pediatric patients across all stages of CKD, particularly in non-Caucasian and obese patients, and may contribute to growth deficits during the earliest stages of CKD.
Assuntos
Insuficiência Renal Crônica/complicações , Deficiência de Vitamina D/complicações , Adolescente , Cálcio/sangue , Criança , Pré-Escolar , Feminino , Florida , Taxa de Filtração Glomerular , Humanos , Hiperparatireoidismo Secundário/complicações , Lactente , Masculino , Obesidade/complicações , Sobrepeso/complicações , Fósforo/sangue , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/fisiopatologia , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Adulto JovemRESUMO
OBJECTIVES: To determine the prevalence of proteinuria in a large cohort of children infected with the human immunodeficiency virus (HIV) and their longitudinal progression during treatment with highly active antiretroviral therapy. STUDY DESIGN: In a retrospective cohort study, 286 children infected with HIV were monitored with quantitative assays of proteinuria from January 1998 through January 2007, with monitoring of viral load, lymphocyte profiles, kidney function, and mortality rates. Proteinuria was quantitated by urine protein to creatinine ratio (Upr/cr). RESULTS: Ninety-four (33%) had proteinuria at baseline. Of these, 32 (11.2%) had nephrotic range proteinuria (Upr/cr > or = 1.0). Initial screening was at 11 +/- 0.3 years of age, with an average follow-up of 5.6 +/- 0.1 years. The mortality rate was significantly greater in those with proteinuria. During the period of observation, 15 patients with nephrotic proteinuria died or had development of end-stage renal disease, and 16 showed improvement. Of those with intermediate range proteinuria (Upr/cr > or = 0.2 < 1.0), 3 progressed to nephrotic range proteinuria, and 39 (63%) showed resolution of the proteinuria (Upr/cr < 0.2). Improvement in proteinuria was correlated with decreasing viral load (r = 0.5; P < .01). CONCLUSIONS: Control of viral load with highly active antiretroviral therapy appears to prevent the progression of HIV-associated renal disease and improve survival rates in infected children.
Assuntos
Nefropatia Associada a AIDS/epidemiologia , Nefropatia Associada a AIDS/etiologia , HIV-1 , Proteinúria/epidemiologia , Proteinúria/etiologia , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Prevalência , Estudos Retrospectivos , Fatores de RiscoRESUMO
El presente artículo revisa el conocimiento actual sobe la patogénesis, significado clínico y opciones terapéuticas en las alteraciones lipídicas que ocurren en niños con enfermedades renales. el perfil lipídico anormal (dislipidemia) tiene una alta prevalencia en niños con síndrome nefrótico, insuficiencia renal crónica y después del transplante renal y, es importante, conocer los difirentes tipos de lipoproteínas y su metabolismo. La patogénesis de estas dislipidemias es multifactorial, inclluyendo un aumento en la síntesis hepática de lípidos y disminución del catabolismo plasmático de lipoproteínas. La dislipidemia severa ha sido propuesta como un factor de riesgo de ateroesclerosis y progresión de la enfermedad renal. De allí que el desarrollo de protocolos de evaluación y tratamiento de la hiperlipidemia (HL) dislipidemia ha surgido como esencial. Sin embargo los beneficios y riesgos del tratamiento con drogas hipolipidemiantes no están establecidos en niños. En esta revisión se dan pautas sobre la evaluación manejo de la HL en niños con enfermedad renal