RESUMO
BACKGROUND AND AIMS: Mulibrey nanism (MUL) is a multiorgan disease caused by recessive mutations in the TRIM37 gene. Chronic heart failure and hepatopathy are major determinants of prognosis in MUL patients, which prompted us to study liver biochemistry and pathology in a national cohort of MUL patients. METHODS: Clinical, laboratory and imaging data were collected in a cross-sectional survey and retrospectively from hospital records. Liver histology and immunohistochemistry for 10 biomarkers were assessed. RESULTS: Twenty-one MUL patients (age 1-51 years) with tumour suspicion showed moderate congestion, steatosis and fibrosis in liver biopsies and marginally elevated levels of serum GGT, AST, ALT and AST to platelet ratio index (APRI) in 20%-66%. Similarly, GGT, AST, ALT and APRI levels were moderately elevated in 12%-69% of 17 MUL patients prior to pericardiectomy. In a cross-sectional evaluation of 36 MUL outpatients, GGT, total bilirubin and galactose half-life (Gal½) correlated with age (r = 0.45, p = .017; r = 0.512, p = .007; r = 0.44, p = .03 respectively). The frequency of clearly abnormal serum values of 15 parameters analysed, however, was low even in patients with signs of restrictive cardiomyopathy. Transient elastography (TE) of the liver revealed elevated levels in 50% of patients with signs of heart failure and TE levels correlated with several biochemistry parameters. Biomarkers of fibrosis, sinusoidal capillarization and hepatocyte metaplasia showed increased expression in autopsy liver samples from 15 MUL patients. CONCLUSION: Liver disease in MUL patients was characterized by sinusoidal dilatation, steatosis and fibrosis with individual progression to cirrhosis and moderate association of histology with cardiac function, liver biochemistry and elastography.
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Técnicas de Imagem por Elasticidade , Nanismo de Mulibrey , Proteínas com Motivo Tripartido , Ubiquitina-Proteína Ligases , Adolescente , Adulto , Biomarcadores , Criança , Pré-Escolar , Estudos Transversais , Humanos , Lactente , Pessoa de Meia-Idade , Nanismo de Mulibrey/genética , Nanismo de Mulibrey/patologia , Mutação , Estudos Retrospectivos , Proteínas com Motivo Tripartido/genética , Ubiquitina-Proteína Ligases/genética , Adulto JovemRESUMO
INTRODUCTION: Low physical activity is a well-recognized problem in pediatric solid organ transplant recipients; however, little is known about the differences between transplant groups. Physical performance testing was performed in a cohort of pediatric kidney, liver, and heart transplant recipients. METHODS: Fifty-one patients (54.9% boys), including 17 liver, 20 kidney, 2 combined liver-kidney, and 12 heart transplant recipients, were tested at the median age of 11.5 (7.5-14.9) years. The results were compared with a control group, which consisted of 425 healthy schoolchildren. The physical performance test included six different tests of endurance, strength, flexibility, and speed. RESULTS: The transplant recipients performed worse on most tests when compared with the control subjects (leg-lift test 42.0 vs. 44.9 repetitions, p = .002; repeated squatting 21.6 vs. 23.9 repetitions, p < .001; sit-up test 9 vs. 17 vs. 9 repetitions, p < .001, back extension 20 vs. 35 repetitions, p < .001; and shuttle run test 26.5 vs. 23.7 seconds, p < .001). None of the test results differed statistically significantly between the transplant groups. CONCLUSION: The physical performance of pediatric solid organ transplant recipients is lower than that of their healthy peers but do not differ between different transplant groups. More systematic rehabilitation programs and follow-up are needed.
Assuntos
Transplante de Órgãos , Desempenho Físico Funcional , Transplantados , Adolescente , Estudos de Casos e Controles , Criança , Feminino , Finlândia , Transplante de Coração , Humanos , Transplante de Rim , Transplante de Fígado , MasculinoRESUMO
BACKGROUND: Unexplained graft fibrosis and inflammation are common after pediatric liver transplantation (LT). OBJECTIVE: We investigated the graft expression of fibrogenic genes and correlated the findings with transplant histopathology and outcome. METHODS: Liver biopsies from 29 recipients were obtained at a median of 13.1 (IQR: 5.0-18.4) years after pediatric LT. Control samples were from six liver-healthy subjects. Hepatic expression of 40 fibrosis-related genes was correlated to histological findings: normal histology, fibrosis with no inflammation, and fibrosis with inflammation. Liver function was evaluated after a subsequent follow-up of 9.0 years (IQR: 8.0-9.4). RESULTS: Patients with fibrosis and no inflammation had significantly increased gene expression of profibrotic TGF-ß3 (1.17 vs. 1.02 p = .005), CTGF (1.64 vs. 0.66 p = .014), PDGF-α (1.79 vs. 0.98 p = .049), PDGF -ß (0.99 vs. 0.76 p = .006), integrin-subunit-ß1 (1.19 vs. 1.02 p = .045), α-SMA (1.12 vs. 0.58 p = .013), type I collagen (0.82 vs. 0.53 p = .005) and antifibrotic decorin (1.15 vs. 0.99 p = .045) compared to patients with normal histology. mRNA expression of VEGF A (0.84 vs. 1.06 p = .049) was lower. Only a few of the studied genes were upregulated in patients with both fibrosis and inflammation. The gene expression levels showed no association with later graft outcome. CONCLUSIONS: Altered hepatic expression of fibrosis-related genes is associated with graft fibrosis without concurrent inflammation.
Assuntos
Transplante de Fígado , Aloenxertos/patologia , Criança , Fibrose , Humanos , Cirrose Hepática/genética , Cirrose Hepática/patologiaRESUMO
BACKGROUND: Data on adult sexual functioning after kidney transplantation (KTx) during childhood or adolescence are scarce. AIM: To assess the long-term sexual and psychosocial quality of life after pediatric KTx. METHODS: 29 young men (median age 27.1 years) were examined 18.7 years (median) after KTx. 56 age-matched healthy men (median age 30.0 years) served as controls. OUTCOME: We studied the influence of sociodemographics, previous renal replacement therapy, current reproductive hormonal serum levels, testicular size, and data on several validated mental and physical questionnaires on participants' Derogatis Interview for Sexual Functioning self-report scores. RESULTS: The KTx recipients had significantly poorer sexual functioning than their healthy peers. KTx men had less frequent sexual activity with a partner (P = .03) and poorer orgasms (P = .002) than the controls but no erectile dysfunction (P = .5). CLINICAL IMPLICATIONS: Depressive symptoms, relationship status, and longer dialysis duration predicted poor adult sexual functioning in KTx recipients, whereas age at transplantation or at the time of the study did not. STRENGTHS & LIMITATIONS: This study contributes extended follow-up data to the very scarce literature on adult sexual functioning in pediatric KTx recipients. Relatively small population and low participation rate limit the comprehensive data interpretation in a population-based cohort of male KTx recipients. CONCLUSION: Sexual functioning is often impaired in young men after pediatric KTx, emphasizing the need for long-term monitoring of sexual health and sexuality as important dimensions of quality of life. Tainio J, Jahnukainen T, Jalanko H, et al. Male Sexual Function After Pediatric Kidney Transplantation-A Cross-sectional Nationwide Study. J Sex Med 2020;17:2104-2107.
Assuntos
Transplante de Rim , Adolescente , Adulto , Criança , Estudos Transversais , Humanos , Transplante de Rim/efeitos adversos , Masculino , Orgasmo , Qualidade de Vida , Comportamento SexualRESUMO
Over the past 30 years, there has been an improvement in both patient and graft survival after pediatric renal transplantation (RTX). Despite this success, these patients still carry an elevated risk for untimely death, partly through premature aging of the vasculature. The aim of this study was thus to investigate the long-term outcome of individuals with RTX in childhood, as well as to explore the cardiovascular health of these adults more than a decade later. We studied 131 individuals who had undergone a RTX between the years 1979 and 2005. Furthermore, left ventricular hypertrophy (LVH), coronary artery calcifications (CAC), and related metabolic factors were investigated in a cross-sectional study including 52 individuals as part of the initial cohort. The mortality rate (n = 131) was 12.2%. The median estimated graft survival was 17.5 years (95% CI 13.6-21.3), being significantly better in children transplanted below the age of 5 years (18.6 vs. 14.3 years, P < 0.01) compared with older ones. CAC were found in 9.8% and LVH in 13% of the patients. Those with cardiac calcifications had longer dialysis vintage and higher values of parathyroid hormone (PTH) during dialysis. Left ventricular mass correlated positively with systolic blood pressure, PTH, and phosphate measured at the time of the study.
Assuntos
Doenças Cardiovasculares/epidemiologia , Sobrevivência de Enxerto , Falência Renal Crônica , Transplante de Rim , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Estudos Transversais , Humanos , Hipertrofia Ventricular Esquerda , Incidência , Falência Renal Crônica/cirurgia , Diálise RenalRESUMO
OBJECTIVES: The aim of the study was to examine the frequency of rickets and bone fractures and to assess areal bone mineral density (aBMD) in childhood among patients with biliary atresia (BA). METHODS: We gathered data on all patients diagnosed with BA in Finland that survived to ≥1 year of age between 1 January 2000 to 30 June 2018. Data on gestational age, birth weight, postsurgical medications, and history of rickets and bone fractures were collected retrospectively. Serum levels of 25-hydroxyvitamin D [25(OH)D] postportoenterostomy (PE) were collected. Plain radiographs and dual energy X-ray absorptiometry (DXA) measurements of study subjects were reviewed. RESULTS: Out of 49 patients, 7 (14%) were diagnosed with rickets during infancy. Clearance of jaundice [odds ratio 0.055, 95% confidence interval [CI] 0.00266-0.393; Pâ<â0.01] was a protective factor against rickets. Sufficient 25(OH)D levels were reached 3 months post-PE. Eleven (22%) patients suffered at least one bone fracture (range 1-9) during childhood and adolescence. In DXA measurements, median lumbar spine aBMD anthropometrically adjusted z-scores were as follows: in native liver survivors 0.8 (interquartile range [IQR] -1.9 to 1.4) at 5 and -0.3 (IQR -1.3 to 0.8) at 10 years and for liver transplanted patients 0.4 (IQR -0.2 to 1.1) at 5 and 0.6 (IQR -0.1 to 1.3) at 10 years. CONCLUSIONS: BA patients have an increased risk for rickets and bone fractures compared with the normal population. Most BA patients have aBMD within normal range between 5 and 10 years of age irrespective of liver transplantation status.
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Atresia Biliar , Densidade Óssea , Absorciometria de Fóton , Adolescente , Atresia Biliar/complicações , Atresia Biliar/cirurgia , Criança , Finlândia/epidemiologia , Humanos , Lactente , Estudos RetrospectivosRESUMO
Congenital nephrotic syndrome (CNS) was primarily considered one disease entity. Hence, one treatment protocol was proposed in the beginning to all CNS patients. Today, with the help of gene diagnostics, we know that CNS is a heterogeneous group of disorders and therefore, different treatment protocols are needed. The most important gene defects causing CNS are NPHS1, NPHS2, WT1, LAMB2, and PLCE1. Before active treatment, all infants with CNS died. It was stated already in the mid-1980s that intensive medical therapy followed by kidney transplantation (KTx) should be the choice of treatment for infants with severe CNS. In Finland, early aggressive treatment protocol was adopted from the USA and further developed for treatment of children with the Finnish type of CNS. The aim of this review is to state reasons for "early aggressive treatment" including daily albumin infusions, intensified nutrition, and timely bilateral nephrectomy followed by KTx at the age of 1-2 years.
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Transplante de Rim , Nefrectomia , Síndrome Nefrótica/terapia , Apoio Nutricional/métodos , Albumina Sérica Humana/administração & dosagem , Humanos , Lactente , Infusões Intravenosas , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/genética , Síndrome Nefrótica/mortalidade , Índice de Gravidade de Doença , Análise de Sobrevida , Tempo para o Tratamento , Resultado do TratamentoRESUMO
BACKGROUND: The prevalence of malignancies after pediatric solid organ transplantation was evaluated in a nationwide study. METHODS: All patients who had undergone kidney, liver, or heart transplantation during childhood between the years 1982 and 2015 in Finland were identified. The inclusion criteria were age under 16 years at transplantation and age over 18 years at the last follow-up day. A total of 233 (137 kidney, 53 liver, and 43 heart) transplant recipients were enrolled. Controls (n = 1157) matched by the year of birth, gender, and hometown were identified using the Population Register Center registry. The cancer diagnoses were searched using the Finnish Cancer Registry. RESULTS: Altogether 26 individuals diagnosed with cancer were found, including 18 transplant recipients. Cancer was diagnosed at a median of 12.0 (IQR 7.8-17.8) years after the transplantation. The transplant recipients' risk for cancer was significantly higher when compared with the controls (HR 14.7; 95% CI 6.4-33.9). There was no difference for different graft types. Sixty-one percent of cancers among the transplant recipients were diagnosed at age older than 18 years. CONCLUSION: The risk for cancer is significantly higher among young adults having undergone solid organ transplantation during childhood in comparison with population controls. Careful follow-up and attention to prevent cancers throughout adulthood are warranted.
Assuntos
Terapia de Imunossupressão/efeitos adversos , Neoplasias/epidemiologia , Transplantados/estatística & dados numéricos , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Finlândia/epidemiologia , Transplante de Coração/efeitos adversos , Transplante de Coração/estatística & dados numéricos , Humanos , Transplante de Rim/efeitos adversos , Transplante de Rim/estatística & dados numéricos , Transplante de Fígado/efeitos adversos , Transplante de Fígado/estatística & dados numéricos , Masculino , Neoplasias/etiologia , Prevalência , Sistema de Registros , Medição de Risco , Adulto JovemRESUMO
BACKGROUND: In Henoch-Schönlein nephritis (HSN), a risk factor for unfavorable outcome is prolonged proteinuria, but the value of renal biopsies in prognosis assessment is debatable. METHODS: We evaluated serial renal biopsies from 26 HSN patients. Follow-up biopsy occurred at median 2.1 years after diagnostic biopsy. Patients formed two groups at the follow-up biopsy: patients without proteinuria (group I; n = 11) and with proteinuria (group II; n = 15). Biopsies underwent evaluation according to three classifications: International Study of Kidney Disease in Children (ISKDC), Oxford (MEST-C), and semiquantitative classification (SQC) including an activity and chronicity score. Analysis also included expression of pro-fibrotic (alpha-smooth muscle actin and vimentin) and inflammatory (P-selectin glycoprotein ligand-1) molecules in the diagnostic biopsy specimens. Definition of unfavorable outcome was active renal disease or reduced renal function at last follow-up. RESULTS: Between the biopsies, SQC chronicity score increased in 22 (85%) patients, whereas activity score and ISKDC grade decreased in 21 (81%) and 17 (65%), respectively. Of the MEST-C parameters, endocapillary proliferation (from 83 to 13%; p < 0.001) and crescents (from 63 to 25%; p = 0.022) showed significant reduction, and segmental glomerulosclerosis (from 38 to 79%; p = 0.006) significant increment. These changes occurred similarly in groups I and II. Expression of the pro-fibrotic and inflammatory molecules showed no clinically significant differences between groups I and II. None in group I and five (33%) patients in group II had unfavorable outcome (p = 0.053). CONCLUSIONS: Our results suggest that follow-up biopsies provide limited additional information to clinical symptoms in HSN outcome prediction.
Assuntos
Vasculite por IgA/patologia , Nefrite/patologia , Adolescente , Biópsia , Estudos de Casos e Controles , Criança , Feminino , Taxa de Filtração Glomerular , Humanos , Vasculite por IgA/complicações , Masculino , Nefrite/etiologia , Proteinúria/etiologia , Estudos RetrospectivosRESUMO
BACKGROUND: Hemolytic uremic syndrome (HUS) is a multisystemic disease. In a nationwide study, we characterized the incidence, clinical course, and prognosis of HUS caused by Shiga toxin (Stx)-producing Escherichia coli (STEC) strains with emphasis on risk factors, disease severity, and long-term outcome. METHODS: The data on pediatric HUS patients from 2000 to 2016 were collected from the medical records. STEC isolates from fecal cultures of HUS and non-HUS patients were collected from the same time period and characterized by whole genome sequencing analysis. RESULTS: Fifty-eight out of 262 culture-positive cases developed verified (n = 58, 22%) STEC-HUS. Another 29 cases had probable STEC-HUS, the annual incidence of STEC-HUS being 0.5 per 100,000 children. Eleven different serogroups were detected, O157 being the most common (n = 37, 66%). Age under 3 years (OR 2.4), stx2 (OR 9.7), and stx2a (OR 16.6) were found to be risk factors for HUS. Fifty-five patients (63%) needed dialysis. Twenty-nine patients (33%) developed major neurological symptoms. Complete renal recovery was observed in 57 patients after a median 4.0 years of follow-up. Age under 3 years, leukocyte count over 20 × 109/L, and need for dialysis were predictive factors for poor renal outcome. CONCLUSIONS: Age under 3 years, stx2, and stx2a were risk factors for HUS in STEC-positive children. However, serogroup or stx types did not predict the renal outcome or major CNS symptoms.
Assuntos
Síndrome Hemolítico-Urêmica/epidemiologia , Adolescente , Fatores Etários , Criança , Pré-Escolar , Creatinina/sangue , Feminino , Síndrome Hemolítico-Urêmica/microbiologia , Síndrome Hemolítico-Urêmica/terapia , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Diálise Renal/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Escherichia coli Shiga Toxigênica/isolamento & purificaçãoRESUMO
It has been proposed that the liver protects the kidney in CLKT. However, few studies have examined long-term renal function after CLKT and contrasted renal function of CLKT patients to KT patients beyond one year after transplantation. We studied long-term renal function of CLKT patients and compared renal function of CLKT patients to KT patients between one and five years after transplantation. Patients who underwent CLKT between 1993 and 2011 were included (n = 34; 11 children and 23 adults). Ninety-six (27 children and 69 adults) KT patients were selected as controls. GFR was estimated (eGFR) and measured (mGFR) with 51 Cr-EDTA clearance. Mean mGFR was 63 at one and 70 at ten years after pediatric CLKT. Mean eGFR was 75 at one and 50 at ten years after adult CLKT. Difference in mean mGFR between pediatric CLKT and KT patients was 8 (95% CI -7 to 23) and 11 (95% CI -4 to 26) at one and five years after transplantation, respectively. Difference in mean eGFR between adult CLKT and KT patients was 8 (95% CI -5 to 20) and 1 (95% CI -10 to 12) at one and five years after transplantation, respectively. Longitudinal changes in GFRs were somewhat similar in CLKT and KT patients in both age-groups but pediatric CLKT patients had on average higher GFRs than pediatric KT patients. In long-term follow-up, renal function remains stable in pediatric CLKT patients but declines in adult CLKT patients.
Assuntos
Doença Hepática Terminal/cirurgia , Falência Renal Crônica/cirurgia , Testes de Função Renal , Transplante de Rim/métodos , Transplante de Fígado/métodos , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Ácido Edético , Doença Hepática Terminal/complicações , Feminino , Finlândia , Taxa de Filtração Glomerular , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Terapia de Imunossupressão , Incidência , Falência Renal Crônica/complicações , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: BKPyV is an important cause of premature graft failure after KT. Most clinical studies describe BKPyV infection in adult KT patients. We studied the prevalence of post-transplant BKPyV viremia, serology, and graft function in pediatric KT recipients. METHODS: Forty-six pediatric patients transplanted between 2009 and 2014 were followed up for BKPyV DNAemia by plasma PCR for median 2.3 (range: 1-6) years. BKPyV-specific antibodies were retrospectively analyzed using virus-like particle ELISA. GFR was measured annually by 51 Cr-EDTA clearance, and serum samples were screened for DSAs by Luminex assay. RESULTS: BKPyV viremia was demonstrated in nine patients at a median of 6 months post-KT. Early BKPyV viremia at 3 months post-KT associated with decreased concomitant GFR and tendency for decreased subsequent graft function. Three of nine patients with BKPyV viremia developed DSA, all against class II antigens. PyVAN developed to four patients and responded to judicious reduction in IS. One graft was lost later due to ABMR. BKPyV-IgG was found in 18 of 31 patients (58%) tested at transplantation, and seven recipients seroconverted after transplantation with a significant increase in IgG levels with IgM. Finally, BKPyV-IgG was detectable in 31 of 40 patients (78%) at the end of the study. CONCLUSIONS: Post-transplant BKPyV viremia in pediatric KT patients may alter graft function and contribute to progression of chronic allograft injury. BKPyV-IgG predicts past exposure. Low or absent BKPyV-specific antibody levels were seen pretransplant in 42% of tested patients, but were not predictive of prolonged replication or poor outcome.
Assuntos
Anticorpos Antivirais/sangue , Vírus BK , Transplante de Rim , Infecções por Polyomavirus/etiologia , Complicações Pós-Operatórias , Infecções Tumorais por Vírus/etiologia , Viremia/etiologia , Adolescente , Formação de Anticorpos , Vírus BK/imunologia , Vírus BK/isolamento & purificação , Biomarcadores/sangue , Criança , Pré-Escolar , Feminino , Finlândia , Seguimentos , Sobrevivência de Enxerto/imunologia , Sobrevivência de Enxerto/fisiologia , Humanos , Lactente , Masculino , Avaliação de Resultados em Cuidados de Saúde , Infecções por Polyomavirus/diagnóstico , Infecções por Polyomavirus/epidemiologia , Infecções por Polyomavirus/imunologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/imunologia , Prevalência , Estudos Retrospectivos , Infecções Tumorais por Vírus/diagnóstico , Infecções Tumorais por Vírus/epidemiologia , Infecções Tumorais por Vírus/imunologia , Viremia/diagnóstico , Viremia/epidemiologia , Viremia/imunologiaRESUMO
Chronic diseases are known to cause premature aging and frailty. Data about telomere length and telomere length-regulating proteins after pediatric KTx are scarce. Leukocyte telomere length and gene expression level of eight telomere-binding proteins were analyzed in 20 KTx recipients, eight childhood NBL survivors, and nine healthy controls. The influence of key clinical parameters on telomere length and on regulators of telomere length was evaluated. The telomere length in the KTx recipients tended to be shorter (0.53 AU) than in the healthy controls (0.64 AU) but longer than in the NBL survivors (0.38 AU). There was no significant difference in telomere length between the NBL survivors and the KTx recipients (P = .110). The gene expression level of telomere length-preserving protein RPA1 was significantly higher in the KTx recipients than among the NBL survivors or healthy controls, while the expression of TRF2 and the tumor suppressor gene p16 was significantly higher in the KTX recipients when compared to the controls. TRF2 and TIN2 correlated significantly with hsCRP; additionally, TRF2 showed significant correlation with plasma creatinine and eGFR. KTx recipients have near to normal telomere length, but they have significantly higher gene expression levels of telomere regulatory proteins compared with healthy controls, suggesting activation of mechanisms preserving telomere length among KTx recipients. Our results suggest that declined graft function and consequent inflammatory response may have influence on telomerase activity.
Assuntos
Sobreviventes de Câncer , Transplante de Rim , Encurtamento do Telômero , Proteínas de Ligação a Telômeros/metabolismo , Adolescente , Adulto , Biomarcadores/metabolismo , Estudos de Casos e Controles , Estudos Transversais , Humanos , Masculino , Adulto JovemRESUMO
BKPyV is widely recognized in KTRs, but little is known about rates of primary and secondary JCPyV exposure in pediatric KTRs. We evaluated JCPyV exposure in pediatric KTRs using antibody responses in the first 12 months post-transplant. Of 46 children transplanted between 2009 and 2014, 6 lacked any samples for serologic testing, leaving 40 KTRs for study. JCPyV-specific IgG and IgM antibodies were measured using a normalized VLP ELISA. Significant JCPyV exposure was defined as IgG seroconversion, increasing IgG levels of >0.5 nOD units, or IgM detection. Of 40 recipients (median age 3.2 years), 11 (27.5%) were seropositive, 20 (50%) seronegative for JCPyV-IgG, while 9 (22.5%) had no specimen at the time of transplantation, but were confirmed as seronegative in post-transplant samples. Of 29 (72.5%) at risk, JCPyV-IgG seroconversion occurred in 15/29 (51.7%) including JCPyV-IgM in 6 patients (20.7%). Two patients (6.9%) developed only JCPyV-IgM. Among JCPyV-IgG-positive KTRs, six (12.5%) had significant IgG increases. Altogether 23 of 40 patients (57.5%) had serological evidence of primary or secondary JCPyV exposure. In these patients, kidney function tended to be lower during the 2 years of follow-up, but only one patient lost the graft due to JCPyV nephropathy. Thus, JCPyV exposure is common in pediatric KTR and may present serologically as primary or secondary infection. Although only one case of JC-PyVAN occurred, a trend toward lower renal function was seen. Dedicated studies of larger cohorts are warranted to define impact of JCPyV in pediatric KTR.
Assuntos
Anticorpos Antivirais/sangue , Vírus JC/imunologia , Transplante de Rim , Adolescente , Formação de Anticorpos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos RetrospectivosRESUMO
We addressed growth of biliary atresia (BA) patients living with native livers between ages 0-6 and effects of post-surgical corticosteroid treatment on growth. Growth charts of 28 BA patients born in Finland between 1987 and 2017 were retrospectively evaluated. Dosage and length of corticosteroid treatment and hydrocortisone substitution were reviewed. At birth, BA patients were shorter (median height - 0.6 (interquartile range (IQR) - 1.3 to - 0.1) SDS, n = 28, P < 0.001) than general population. Height remained stable during early childhood (median height - 0.6 (IQR - 1.4 to 0.1) SDS for girls and - 0.4 (IQR - 1.6 to 0.2) SDS for boys at 6 years of age). Patients were of normal height adjusted weight at 6 years with a median age and sex-adjusted body mass index (ISO-BMI) of 20.9 (IQR 19.3 to 25.0) for girls and 22.1 (IQR 20.7 to 25.6) for boys. Higher (≥ 50 mg/kg) cumulative post-portoenterostomy prednisolone dosage resulted in 0.18 SDS lower height per treatment week (ß - 0.18, SE 0.04, P < 0.001) compared to lower dosage (< 50 mg/kg).Conclusion: BA patients grow normally during early childhood. As high postoperative corticosteroid dosage has a short-term negative effect on height, very high dosages should be avoided. What Is Known: ⢠Growth of biliary atresia patients has mostly been shown to be within normal limits ⢠Corticosteroids may decrease growth rate What Is New: ⢠Biliary atresia patients surviving with their native livers are shorter than general population and their mid-parental target height at birth ⢠A high (> 50 mg/kg) cumulative prednisolone dosage has a negative transitory impact on height gain after portoenterostomy.
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Atresia Biliar/tratamento farmacológico , Estatura/efeitos dos fármacos , Glucocorticoides/farmacologia , Portoenterostomia Hepática , Atresia Biliar/fisiopatologia , Atresia Biliar/cirurgia , Criança , Pré-Escolar , Terapia Combinada , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Glucocorticoides/uso terapêutico , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: Although liver disease is a major complication of parenteral nutrition (PN) for intestinal failure (IF), its pathogenesis remains unclear. We investigated potential molecular mechanisms of liver injury in pediatric onset IF. METHODS: Liver expression of canalicular phospholipid (ABCB4), bile acid (ABCB11), and sterol (ABCG5/8) transporters, their upstream regulators LXR and FXR as well as pro-inflammatory cytokines interleukin-6 (IL6) and tumor necrosis factor (TNF) were investigated among patients with IF [age median 3.8 (IQR 1.2 to 11)] in relation to biochemical and histologic liver injury, PN, serum plant sterols, fibroblast growth factor 19, and α-tocopherol. RESULTS: Patients receiving PN currently (n = 18) showed more advanced liver injury than patients after weaning off PN (n = 30). Histologic portal inflammation strongly segregated PN-dependent (44%) from weaned off patients (3%, P = 0.001) and coupled with progression of cholestasis and liver fibrosis. Patients with portal inflammation demonstrated markedly induced liver RNA expression of IL6 and TNF, repression of FXR and its canalicular bile transporter target gene RNA expression, including ABCB4 and ABCB11 as well as decreased protein expression of ABCB11 and ABCB4. Furthermore, upregulation of LXR and ABCG5/8 RNA expression was suppressed in patients with portal inflammation. Current PN, increased serum levels of plant sterols stigmasterol, avenasterol, and sitosterol along with serum citrulline, a marker of enterocyte mass, predicted portal inflammation. CONCLUSIONS: In pediatric onset IF, current PN delivery synergistically with intestinal compromise promote liver inflammation, which associates with progression of biochemical and histologic liver injury, while reducing expression of canalicular bile transporters.
Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Enteropatias/complicações , Hepatopatias/etiologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Membro 11 da Subfamília B de Transportadores de Cassetes de Ligação de ATP/metabolismo , Membro 5 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Membro 8 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Biomarcadores/metabolismo , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos Transversais , Regulação para Baixo , Feminino , Hepatite/diagnóstico , Hepatite/etiologia , Hepatite/metabolismo , Humanos , Imuno-Histoquímica , Lactente , Enteropatias/terapia , Lipoproteínas/metabolismo , Hepatopatias/diagnóstico , Hepatopatias/metabolismo , Masculino , Nutrição Parenteral/efeitos adversos , Fatores de Risco , Regulação para CimaRESUMO
Cancer after liver transplantation (LT) constitutes a threat also for young recipients, but cancer risk factors are usually absent in children and large studies on the cancer risk profile in young LT recipients are scarce. Data of patients younger than 30 years who underwent LT during the period 1982-2013 in the Nordic countries were linked with respective national cancer registries to calculate standardized incidence ratios (SIRs). A total of 37 cancer cases were observed in 923 patients with 7846 person-years of follow-up. The SIR for all cancer types, compared with the matched general population, was 9.8 (12.4 for males and 7.8 for females). Cumulative incidence of cancer adjusted for the competing risk of death was 2% at 10 years, 6% at 20 years, and 22% at 25 years after LT. Non-Hodgkin lymphoma was the most common cancer type (n = 14) followed by colorectal (n = 4) and hepatocellular cancer (n = 4). Age was a significant risk factor for cancer, and the absolute risk of most cancers (except for lymphoma) increased considerably in young adults older than 20 years. The cancer risk pattern is different in pediatric and young LT patients compared with adult recipients. The striking increase in cancer incidence in young adulthood after the second decade of life deserves further consideration in transition programs.
Assuntos
Transplante de Fígado/efeitos adversos , Neoplasias/epidemiologia , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Neoplasias/diagnóstico , Sistema de Registros , Fatores de Risco , Países Escandinavos e Nórdicos/epidemiologia , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Data about health-related quality of life (HRQOL) in adult recipients after pediatric kidney transplantation (KTx) are scarce. In this nationwide questionnaire-based study, HRQOL and social status in young adult men having undergone KTx during childhood (n = 29) were studied and compared to age- and gender-matched healthy controls (n = 56) and survivors of childhood acute lymphoblastic leukemia (n = 52) comprising controls with another chronic disease of childhood. Altogether 41% of the KTx recipients, 50% of the leukemia survivors and 80% of the healthy controls lived in a permanent relationship. When compared with leukemia survivors, the KTx recipients reported significantly more bodily pain and worse general health (RAND-36). Older age at time of study, longer duration of dialysis, multiple transplantations and diminished graft function correlated with lower scores. The KTx recipients had a significantly higher mean Beck Depression Inventory (BDI) score than the leukemia survivors (P = 0.000) or the healthy controls (P = 0.006). BDI scores were highest in patients who lived without a partner or children had lower educational level or were unemployed. KTx recipients had significantly lower HRQOL scores than their healthy and controls with childhood chronic disease. Early detection of psychosocial problems and poor physical functioning among these patients is warranted.
Assuntos
Transplante de Rim/psicologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/psicologia , Qualidade de Vida , Sobreviventes/psicologia , Adulto , Fatores Etários , Criança , Estudos Transversais , Finlândia , Humanos , Transplante de Rim/métodos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Valores de Referência , Estudos Retrospectivos , Medição de Risco , Fatores Sexuais , Perfil de Impacto da Doença , Estatísticas não Paramétricas , Adulto JovemRESUMO
We related hepatic gene and serum expression of matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) to liver histology in pediatric LT recipients. Liver biopsies and serum samples were obtained from 52 patients 10.6 years post-LT and age-matched controls for analyses of MMPs and TIMPs. Patients with fibrosis had significantly higher hepatic gene expression of MMP-2, MMP-9, MMP-14, TIMP-1, and TIMP-2 than patients without. Expression of these genes correlated with graft Metavir fibrosis stage (r = 0.494-0.684, P ≤ 0.006 for all). Gene expression of MMP-1, MMP-3, MMP-8, TIMP-3, and TIMP-4 was undetectable in both patients and controls. Portal inflammation and cytokeratin 7 correlated positively with gene expression of TIMP-1. Gene expression of MMP-2, MMP-9, and TIMP-2 correlated negatively with the time of low-dose cortisone usage (r = -0.448 to -0.422, P < 0.05 for all). Serum concentrations of MMP-8 and TIMP-1 were significantly increased and MMP-9 decreased among patients compared with controls, but no correlations to graft histology or gene expression were observed. Hepatic gene expression of certain MMPs and TIMPs is increased in stable pediatric LT recipients displaying graft fibrosis, but this did not reflect to their serum concentrations. Increased hepatic gene expression of TIMP-1 correlated with graft fibrosis stage, inflammation, and chronic cholestasis.
Assuntos
Transplante de Fígado , Fígado/enzimologia , Metaloproteinases da Matriz/sangue , Inibidores Teciduais de Metaloproteinases/sangue , Adolescente , Adulto , Criança , Estudos Transversais , Feminino , Fibrose , Expressão Gênica , Humanos , Terapia de Imunossupressão , Queratina-7/metabolismo , Fígado/patologia , Masculino , Adulto JovemRESUMO
OBJECTIVES: The aim of the study was to evaluate health-related quality of life (HRQoL) and parental distress in a national cohort of children with biliary atresia (BA) with their native livers in relation to BA complications and HRQoL of normal population controls. METHODS: We invited all Finnish children with BA surviving with their native livers at age 2 to 18 years to participate in 2009 and in 2014. Parents filled the Pediatric Quality of Life Inventory (PedsQL) proxy questionnaire, a survey of their child's health and evaluated parental distress on a visual-analog scale from 0 to 7. Overall participation rates were 80% (12/15) for the longitudinal and 83% (20/24) for the cross-sectional assessment. A control population of 324 children matched for age and sex was randomly picked, and 108 (33%) participated. RESULTS: Overall, patients and controls had comparable HRQoL. Patients reported significantly lower scores for school functioning (Pâ=â0.004) as depicted by missing school or day care due to hospital visits. Eighty-five percent of parents reported extreme worry (7.0) when hearing their child's BA diagnosis. At 6 years after diagnosis, parents reported significantly less worry: median score 3.8 (interquartile range 3.0-5.4, Pâ<â0.001 for difference). Parents of patients with optimal health were less worried than parents whose children's health was suboptimal: median worry score 3.3 (3.0-4.8) versus 5.3 (3.8-5.9), Pâ=â0.05. CONCLUSIONS: BA patients' HRQoL was comparable to matched peers in general but reduced by missing school days due to frequent hospital visits. At diagnosis, parents experienced considerable worry that diminished over the years after successful portoenterostomy, especially if the child's health was optimal.