RESUMO
BACKGROUND: Children with chronic kidney disease are frequently born small for gestational age (SGA) and prone to disproportionately short stature. It is unclear how SGA affects growth after kidney transplantation (KTx). METHODS: Linear growth (height, sitting height, and leg length) was prospectively investigated in a cohort of 322 pediatric KTx recipients, with a mean follow-up of 4.9 years. Sitting height index (ratio of sitting height to total body height) was used to assess body proportions. Predictors of growth outcome in KTx patients with (n = 94) and without (n = 228) an SGA history were evaluated by the use of linear mixed-effects models. RESULTS: Mean z-scores for all linear body dimensions were lower in SGA compared with non-SGA patients (p < 0.001). SGA patients presented with higher target height deficit and degree of body disproportion (p < 0.001). The latter was mainly due to reduced leg growth during childhood. Pubertal trunk growth was diminished in SGA patients, and the pubertal growth spurt of legs was delayed in both groups, resulting in further impairment of adult height, which was more frequently reduced in SGA than in non-SGA patients (50 % vs 18 %, p < 0.001). Use of growth hormone treatment in the pre-transplant period, preemptive KTx, transplant function, and control of metabolic acidosis were the only potentially modifiable correlates of post-transplant growth in SGA groups. By contrast, living related KTx, steroid exposure, and degree of anemia proved to be correlates in non-SGA only. CONCLUSIONS: In children born SGA, growth outcome after KTx is significantly more impaired and affected by different clinical parameters compared with non-SGA patients.
Assuntos
Transtornos do Crescimento/etiologia , Transplante de Rim/métodos , Insuficiência Renal Crônica/cirurgia , Adolescente , Envelhecimento , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Crescimento , Humanos , Lactente , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Perna (Membro)/crescimento & desenvolvimento , Modelos Lineares , Masculino , Estudos Prospectivos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/patologia , Maturidade Sexual , Tórax/crescimento & desenvolvimentoRESUMO
Acute antibody-mediated rejection is a diagnostic challenge in renal transplantation medicine. However, it is an important diagnosis to make, since chronic antibody-mediated rejection (CAMR) is the main cause of long-term graft loss. Antibody-mediated rejection is diagnosed by detecting donor-specific antibodies (DSAs) in the blood in combination with observing typical histomorphological signs in kidney biopsy, as described in the Banff classification. Therapy is based on the removal of DSAs by administering intravenous immunoglobulins (IVIGs), plasmapheresis, or immunoadsorption. Reoccurrence of antibodies is diminished by the use of rituximab, increased immunosuppression, and in some cases additional experimental substances. A combination of these techniques has been shown to be successful in the majority of cases of acute and chronic antibody-mediated rejection. Routine DSA monitoring is warranted for early detection of antibody-mediated rejection.
Assuntos
Anticorpos/imunologia , Rejeição de Enxerto/imunologia , Transplante de Rim , Doença Aguda , Criança , Doença Crônica , Rejeição de Enxerto/patologia , Antígenos HLA/imunologia , HumanosRESUMO
The mammalian target of the rapamycin (mTOR) inhibitors sirolimus and everolimus are increasingly being used in pediatric kidney transplantation in different combinations and doses. Several studies have shown beneficial effects of using mTOR inhibitors in children after pediatric renal transplantation. A switch to a low-dose calcineurin inhibitor (CNI) and mTOR inhibitor has been proven to stabilize the glomerular filtration rate. Additionally, de novo studies using a low-dose CNI and an mTOR inhibitor have shown good graft survival and a low number of rejections. Side effects of mTOR inhibitors, such as hyperlipidemia, wound healing problems, and proteinuria, mainly occur if high doses are given and if treatment is not combined with a CNI. Lower doses of mTOR inhibitors do not result in growth impairment or reduced testosterone levels. Treatment with mTOR inhibitors is also associated with a lower number of viral infections, especially cytomegalovirus. Due to their antiproliferative effect, mTOR inhibitors could theoretically reduce the risk of post-transplant lymphoproliferative disease. mTOR inhibitors, especially in combination with low-dose CNIs, can safely be used in children after kidney transplantation as de novo therapy or for conversion from CNI- and mycophenolate mofetil-based regimens.
Assuntos
Imunossupressores/uso terapêutico , Transplante de Rim , Serina-Treonina Quinases TOR/antagonistas & inibidores , Animais , Inibidores de Calcineurina/uso terapêutico , Criança , Infecções por Citomegalovirus/prevenção & controle , Aprovação de Drogas , Everolimo , Hormônios Esteroides Gonadais/sangue , Rejeição de Enxerto/prevenção & controle , Humanos , Transplante de Rim/efeitos adversos , Transtornos Linfoproliferativos/prevenção & controle , Sirolimo/efeitos adversos , Sirolimo/análogos & derivados , Sirolimo/uso terapêutico , Cicatrização/efeitos dos fármacosRESUMO
BACKGROUND: The aim of this study was to analyze the neurological involvement and outcome in pediatric patients with hemolytic uremic syndrome (HUS) during the 2011 epidemic caused by Escherichia coli O104:H4. METHODS: Clinical data and data from magnetic resonance imaging (MRI) scans and electroencephalography (EEG) during the acute phase of the disease and during follow-up at 3 and 6 months were analyzed in 50 patients. Twenty-five of these patients underwent neuropsychological testing (WISC IV) during follow-up. RESULTS: Neurological involvement (stupor or coma, seizures, visual disturbances, paresis, myocloni) was initially observed in 14/50 (28%) patients. One patient died. EEG abnormalities were more frequent in patients with neurological involvement than in those without (12/14 vs. 13/25, respectively). Cranial MRI scans were analyzed in nine patients with neurological involvement, of whom five showed abnormal findings. At the 3- and 6-month follow-ups, EEG abnormalities were found in 14/40 (35%) and 7/36 (19%) patients, respectively, whereas 28/42 (67%) and 17/39 (44%) patients, respectively, complained about on-going reduced performance. Neuropsychological testing showed a slightly lower global intelligence quotient in patients with neurological involvement versus those without (113.4 ± 2.8 vs. 119.4 ± 1.8, respectively). CONCLUSIONS: Neurological involvement was frequent in our cohort. Accordingly, the incidence of pathological EEG findings was high, even in patients without clinical signs of neurological involvement. Nevertheless, major neurological sequelae were rare, and neuropsychological outcome was favorable after 6 months.
Assuntos
Doenças do Sistema Nervoso Central/epidemiologia , Doenças do Sistema Nervoso Central/microbiologia , Infecções por Escherichia coli/complicações , Síndrome Hemolítico-Urêmica/complicações , Adolescente , Doenças do Sistema Nervoso Central/fisiopatologia , Criança , Pré-Escolar , Eletroencefalografia , Feminino , Síndrome Hemolítico-Urêmica/microbiologia , História Antiga , Humanos , Imageamento por Ressonância Magnética , MasculinoRESUMO
Protocol biopsies (PB) are seldom performed after pediatric kidney transplantation (KTx), and factors influencing PB results have not previously been investigated. We performed PB in 79 children six months after KTx and evaluated the results using Banff 2007 criteria. Complications such as bleeding or infections were not detected. The influence of different variables on PB results was evaluated by covariance analysis. Children treated with a low-dose calcineurin inhibitor (CNI) together with an mTOR inhibitor exhibited decreased subclinical rejection (0% vs. 19%, p = 0.001) and decreased interstitial fibrosis and tubular atrophy (IF/TA) (15% vs. 42%, p = 0.013) compared with patients treated with a conventional regimen consisting of normal-dose CNI and mycophenolate mofetil. Children with IF/TA had a lower GFR four wk after Tx (83 ± 22 vs. 62 ± 20 mL/min/1.73 m(2) , p = 0.001). Cold ischemia time, living-related donors, pre-emptive KTx, and donor age did not influence PB results. Treatment with low-dose CNI and mTOR inhibitor and high GFR directly after Tx are the main factors associated with less inflammation and fibrosis in PB and might therefore lead to better long-term graft function.
Assuntos
Ciclosporina/administração & dosagem , Rejeição de Enxerto/patologia , Imunossupressores/administração & dosagem , Transplante de Rim , Rim/patologia , Tacrolimo/administração & dosagem , Adolescente , Biópsia , Criança , Pré-Escolar , Ciclosporina/uso terapêutico , Relação Dose-Resposta a Droga , Esquema de Medicação , Quimioterapia Combinada , Everolimo , Feminino , Fibrose/etiologia , Fibrose/patologia , Fibrose/prevenção & controle , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Humanos , Imunossupressores/uso terapêutico , Rim/fisiologia , Masculino , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapêutico , Cuidados Pós-Operatórios , Complicações Pós-Operatórias/patologia , Complicações Pós-Operatórias/prevenção & controle , Prednisolona/uso terapêutico , Sirolimo/análogos & derivados , Sirolimo/uso terapêutico , Tacrolimo/uso terapêutico , Resultado do TratamentoRESUMO
Concerns have been raised that mammalian target of rapamycin inhibitors in pediatric transplant recipients might interfere with longitudinal bone growth by inhibition of growth factor signaling and growth plate chondrocyte proliferation. We therefore undertook a prospective nested, case-control study on longitudinal growth over 2 years in steroid-free pediatric renal transplant recipients. Fourteen patients on a steroid-free maintenance immunosuppressive regimen consisting of low-dose everolimus (EVR) in conjunction with low-dose cyclosporine (CsA) were compared to a matched cohort of 14 steroid-free patients on a standard dose mycophenolate mofetil (MMF) regimen in conjunction with a standard dose calcineurin inhibitor (CNI). The mean change in height standard deviation (SD) score in the first study year was 0.31 ± 0.71 SD score in the EVR group compared to 0.31 ± 0.64 SD score in the MMF group (P = 0.20). For the entire study period of 2 years, the change in height SD score in the EVR group was 0.43 ± 0.81 SDS compared to 0.75 ± 0.85 SDS in the MMF group (P = 0.32). The percentage of prepubertal patients experiencing catch-up growth, defined as an increase in height SD score ≥0.5 in 2 years, was similar in the EVR group (5/8, 65%) and the MMF group (6/8, 75%; P = 1.00). Longitudinal growth over 2 years in steroid-free pediatric patients on low-dose EVR and CsA is not different to that of a matched steroid-free control group on an immunosuppressive regimen with standard-dose CNI and MMF. Hence, low-dose EVR does not appear to negatively impact short-term growth in pediatric renal transplant recipients.
Assuntos
Estatura/efeitos dos fármacos , Ciclosporina/administração & dosagem , Imunossupressores/administração & dosagem , Ácido Micofenólico/análogos & derivados , Sirolimo/análogos & derivados , Adolescente , Desenvolvimento Ósseo/efeitos dos fármacos , Estudos de Casos e Controles , Criança , Everolimo , Feminino , Humanos , Transplante de Rim , Masculino , Ácido Micofenólico/administração & dosagem , Prednisolona/administração & dosagem , Estudos Prospectivos , Sirolimo/administração & dosagemRESUMO
BACKGROUND: No adequate statistical model has been established to estimate future glomerular filtration rate (GFR) in children after kidney transplantation (KTX). Equations based on simple linear regression analysis as used in adults are not established in children. METHODS: An optimal prognostic model of GFR was generated for 63 children at 3-7 years after KTX. The main regression model for prediction of the log-transformed GFR (logGFR) included the mean monthly change of GFR in the period 3-24 months after KTX (∆GFR), the baseline GFR at 3 months (bGFR), and an intercept. Additionally, we investigated if the inclusion of cofactors leads to more precise predictions. The model was validated by leave-one-out cross-validation for years 3-7 after KTX. Prognostic quality was determined with the mean squared error (MSE) and mean absolute error (MAE). Results were compared with the simple linear regression model used in adults. RESULTS: The following statistical model was calculated for every prognosis year (i = 3, , 7):[Formula: see text] [Formula: see text] Comparison of the new statistical model and the simple linear model for adults led to relevantly lower MSEs and MAEs for the new model (year 7: New model: MSE 0.1, MAE 0.3/adult model: MSE 1069, MAE 18). The benefit of inclusion of cofactors was not relevant. CONCLUSIONS: This statistical model is able to predict long-term graft function in children with very high precision.
Assuntos
Taxa de Filtração Glomerular , Sobrevivência de Enxerto , Transplante de Rim , Rim/fisiopatologia , Rim/cirurgia , Modelos Estatísticos , Adulto , Fatores Etários , Criança , Pré-Escolar , Feminino , Humanos , Transplante de Rim/efeitos adversos , Modelos Lineares , Masculino , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: In May and June 2011 the largest known outbreak of hemolytic uremic syndrome (HUS) occurred in northern Germany. Because, quite unusually, a large number of adults was affected and the causative Escherichia coli strain, serotype O104:H4, showed an atypical virulence factor pattern, it was speculated that this outbreak was associated with an aggressive course and an unfavorable prognosis also in children. METHODS: Retrospective analysis of medical records of 90 children and comparison to previous outbreak and sporadic case series. RESULTS: Median age was unusually high (11.5 years) compared with that in historical series. Only 1 patient (1.1%) died in the acute phase. Most patients (67/90 [74%]) received supportive care only. Renal replacement therapy was required in 64 of 90 (71%) of the children. Neurological complications, mainly seizures and altered mental stage, were present in 23 of 90 (26%) patients. Ten patients received plasmapheresis, 6 eculizumab, and 7 a combination of both. After a median follow-up of 4 months, renal function normalized in 85 of 90 (94%) patients, whereas 3 patients had chronic kidney disease stage 3 or 4, and 1 patient (1.1%) still requires dialysis. Complete neurological recovery occurred in 18 of 23 patients. Mild to moderate and major residual neurological changes were present in 3 patients and 1 patient, respectively, although all patients were still improving. CONCLUSIONS: E. coli O104:H4 caused the largest HUS outbreak in children reported in detail to date and most patients received supportive treatment only. Initial morbidity, as well as short-term outcome, due to this pathogen, is comparable to previous pediatric series of Shiga toxin-producing E. coli HUS.
Assuntos
Surtos de Doenças , Síndrome Hemolítico-Urêmica/epidemiologia , Escherichia coli Shiga Toxigênica/classificação , Escherichia coli Shiga Toxigênica/isolamento & purificação , Adolescente , Criança , Pré-Escolar , Feminino , Alemanha/epidemiologia , Humanos , Lactente , Masculino , Terapia de Substituição Renal/métodos , Estudos Retrospectivos , Escherichia coli Shiga Toxigênica/genética , Resultado do TratamentoRESUMO
BACKGROUND: To date, no study has described the pre-transplant and transplant risk factors for end-organ damage based on arterial hypertension in children after kidney transplantation (KTX). METHODS: A retrospective chart review was performed of 206 children with KTX between 1991 and 2007. Patients<120 cm were excluded as no validated percentiles for 24-h ambulant blood pressure monitoring (ABPM) exist. Complete data sets were available for 116 patients. Data were recorded at 12, 24 and 36 months post- KTX. We analysed the influence of donor age, age at transplantation, pre-emptive transplantation, living or deceased transplantation and glomerular filtration rate (GFR) on the presence of end-organ damage, ABPM, ABPM standard deviation score and the numbers of anti-hypertensives used. RESULTS: Lower donor age and the decade of transplantation were associated with less detection of end-organ damage (P=0.001). A lower need for anti-hypertensive medication (P=0.001) was detected in children who received organs from living donors and from deceased donors with a donor age<35 years and who were transplanted pre-emptively. Low recipient age was the only factor associated with lower ABPM (P=0.001). In our study, the type of immunosuppressive regimen and the GFR had no influence on the blood pressure. CONCLUSIONS: It may be speculated that the risk of arterial hypertension and associated end-organ damage in children after KTX could be reduced by using organs from young donors with an advantage for living related and pre-emptive donation.
Assuntos
Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto , Hipertensão/prevenção & controle , Falência Renal Crônica/cirurgia , Transplante de Rim/mortalidade , Doadores Vivos , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Feminino , Seguimentos , Alemanha/epidemiologia , Taxa de Filtração Glomerular , Rejeição de Enxerto/etiologia , Humanos , Imunossupressores/uso terapêutico , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Adulto JovemRESUMO
PURPOSE OF REVIEW: The use of everolimus has recently emerged for solid-organ transplantation in children. This review gives an overview of the relevant studies and clinical trials involving the immunosuppressive effects of everolimus in child organ transplant. RECENT FINDINGS: The use of everolimus in pediatric organ transplantation is associated with a decrease in calcineurin inhibitor-related toxicity, better renal function, a low number of acute rejections, and an acceptable side-effect profile. Particularly, the use of everolimus reduces the incidence of virus infection and the risk of posttransplant lymphoproliferative disease. SUMMARY: Everolimus is an effective agent with several advantages for pediatric solid-organ transplantation. Future prospective, randomized controlled trials will have to be performed in order to validate the findings of these pilot trials.
Assuntos
Imunossupressores/uso terapêutico , Transplante de Órgãos/métodos , Sirolimo/análogos & derivados , Criança , Everolimo , Humanos , Pediatria/métodos , Sirolimo/uso terapêutico , Imunologia de TransplantesRESUMO
Regional citrate anticoagulation (RCA) has been considered to be a standard component of pediatric apheresis therapy for more than a decade. However, data on dosing recommendations and evaluations of the effectiveness and safety of anticoagulation are rarely found in published reports. The aim of this retrospective analysis was to present our single-center experience with RCA in pediatric apheresis therapy with the aim of developing an operating procedure. Five children aged 7-14 years underwent a total of 72 (range 3-44) therapeutic apheresis sessions with RCA in the form of immunoadsorption therapy (2 patients), low-density lipoprotein (LDL)-apheresis (1 patient), and plasmapheresis (two patients). A 3% citrate solution was used. Citrate flow was started at 4.0% of the blood flow velocity and was adapted to match post-filter ionized calcium levels ≤ 0.30 mmol/l. Once the patient's ionized calcium fell to <1.05 mmol/l, an intravenous 10% calcium gluconate solution was administered. Twenty pediatric apheresis patients who received standard heparinization, matched for age, body surface area, processed plasma volume, and blood flow velocity, were enrolled in the study as a comparison group. No side effects were experienced in 72 apheresis session. The 3% citrate solution had to be reduced gradually during the apheresis session and was infused at a mean of 2.8-3.8% of the blood flow rate. Serum bicarbonate levels before and after the apheresis session with RCA [23.9 (range 18.9-30.1) vs. 26.3 (20.2-33.0) mmol/l, respectively] were significantly different (p=0.013). All patients required intravenous calcium substitution to maintain serum calcium levels within the physiological range. Due to the administration of the 3% citrate solution and calcium, all patients significantly gained weight during the procedure, with a median weight gain of 2.5% (p<0.001). The extra fluid load caused problems in patients with kidney failure. Our regimen with RCA is safe, feasible, and effective in pediatric therapeutic apheresis therapy. For RCA in apheresis, we recommend (1) a citrate (3%) flow of 3.3% of the blood flow, (2) prophylactic intravenous calcium substitution from the beginning, and (3) a more highly concentrated citrate solution in the case of oliguric patients.
Assuntos
Anticoagulantes/administração & dosagem , Bicarbonatos/sangue , Remoção de Componentes Sanguíneos/métodos , Líquidos Corporais/metabolismo , Cálcio/administração & dosagem , Citratos/administração & dosagem , Adolescente , Anticoagulantes/efeitos adversos , Cálcio/efeitos adversos , Criança , Citratos/efeitos adversos , Feminino , Humanos , Masculino , Estudos RetrospectivosRESUMO
The mineral and bone disorder of chronic kidney disease remains a challenging complication in pediatric end-stage renal disease. Here, we assessed symptoms, risk factors and management of this disorder in 890 children and adolescents from 24 countries reported to the International Pediatric Peritoneal Dialysis Network Registry. Signs of this disease were most common in North American patients. The prevalence of hyperphosphatemia increased with age from 6% in young infants to 81% in adolescents. Serum parathyroid hormone (PTH) was outside the guideline targets in the majority of patients and associated with low calcium, high phosphorus, acidosis, dialysis vintage and female gender. Serum calcium was associated with dialytic calcium exposure, serum phosphorus with low residual renal function and pubertal status. PTH levels were highest in Latin America and lowest in Europe. Vitamin D and its active analogs were most frequently administered in Europe; calcium-free phosphate binders and cinacalcet in North America. Clinical and radiological symptoms markedly increased when PTH exceeded 300 pg/ml, the risk of hypercalcemia increased with levels below 100 pg/ml, and time-averaged PTH concentrations above 500 pg/ml were associated with impaired longitudinal growth. Hence, the symptoms and management of the mineral and bone disorder of chronic kidney disease in children on peritoneal dialysis showed substantial regional variation. Our findings support a PTH target range of 100-300 pg/ml in the pediatric age group.
Assuntos
Hiperfosfatemia/tratamento farmacológico , Hiperfosfatemia/etiologia , Hipocalcemia/tratamento farmacológico , Hipocalcemia/etiologia , Falência Renal Crônica/complicações , Diálise Peritoneal , Adolescente , Cálcio/sangue , Criança , Pré-Escolar , Cinacalcete , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Humanos , Hiperfosfatemia/epidemiologia , Hipocalcemia/epidemiologia , Lactente , Falência Renal Crônica/sangue , América Latina/epidemiologia , Masculino , Naftalenos/uso terapêutico , América do Norte/epidemiologia , Hormônio Paratireóideo/sangue , Proteínas de Ligação a Fosfato/uso terapêutico , Fósforo/sangue , Estudos Prospectivos , Sistema de Registros , Vitamina D/uso terapêutico , Adulto JovemRESUMO
BACKGROUND: Hyperphosphataemia in patients with chronic kidney disease (CKD) is associated with mineral and bone disorder and increased cardiovascular mortality. Despite phosphate binders (PB), nutrition counselling and dialysis therapy, the prevalence of hyperphosphataemia remains unacceptably high. It was hypothesized that an inadequate relation of PB dose to meal inorganic phosphorus (iP) content may be an important factor for failure of phosphate management. METHODS: The innovative 'Phosphate Education Program' (PEP) bases on patient empowerment to eye-estimate meal iP content by newly defined 'Phosphate Units' (PU; 1 PU per 100 mg phosphorus) and self-adjust PB dosage to dietary iP intake by an individually prescribed PB/PU ratio (PB pills per PU). In a prospective study, 16 children (aged 4-17 years) with CKD and their parents were trained with the PEP concept and followed up for 24 weeks for changes in serum electrolyte levels, dietary behaviour and PB dose. RESULTS: Within 6 weeks after PEP training, the percentage of children with serum phosphate (PO) >1.78 mmol/l dropped from 63% (10/16) to 31% (5/16). Mean serum PO level decreased from 1.94 ± 0.23 at baseline to 1.68 ± 0.30 (SD) mmol/l in Week 7-12 (P = 0.02) and to 1.78 ± 0.36 (SD) mmol/l in Week 19-24 (P = 0.2), whereas serum calcium [2.66 ± 0.3 vs 2.60 ± 0.23 (SD) mmol/l in Weeks 7-12 (P = 0.45) and 2.66 ± 0.23 (SD) mmol/l in Week 19-24 (P = 0.21)] and serum potassium [4.69 ± 0.48 vs 4.58 ± 0.68 (SD) mmol/l in Week 7-12 (P = 0.40) and 4.65 ± 0.49 (SD) mmol/l in Week 19-24 (P = 0.73)] remained unchanged. The mean daily PB dose rose from 6.3 ± 2.9 to 8.2 ± 5.4 (SD) pills during observation period with an increased meal-to-meal variability (P = 0.04). Dietary iP intake was not affected by PEP concept. CONCLUSION: The empowerment of children with CKD and their parents to self-adjust PB dose to eye-estimated meal iP content significantly improved management of hyperphosphataemia without reducing dietary iP intake.
Assuntos
Hiperfosfatemia/tratamento farmacológico , Nefropatias/tratamento farmacológico , Fosfatos/metabolismo , Adolescente , Criança , Pré-Escolar , Doença Crônica , Comportamento Alimentar , Seguimentos , Humanos , Hiperfosfatemia/sangue , Adesão à Medicação , Satisfação do Paciente , Fosfatos/administração & dosagem , Estudos ProspectivosRESUMO
Recent years has seen an increasing use of regional citrate anticoagulation in pediatric dialysis. Several approaches have been described for monitoring anticoagulation in the extracorporeal circuit, such as serum citrate levels, post-filter ionized calcium (iCa), and activated coagulation time (ACT). However, no standard recommendations have yet been established for applying any of these parameters, especially for iCa. The objective of this retrospective analysis was to establish adequate coagulation management using post-filter iCa values. Normal values for ACTester-based ACT were established using a group of 64 children who were divided into two subgroups, with one subgroup comprising children without chronic kidney disease or coagulation disorder (age 1.2-17.5 years, median 9.7 years) and one consisting of 32 uremic patients (age 0.6-17.5 years, median 13.7 years). In a second group of 13 patients (aged 7-17 years), all of whom were undergoing high-flux dialysis (HD) with regional citrate anticoagulation (RCA), we assessed 73 post-filter blood samples for ionized calcium and ACT. A receiver operating characteristic graph was used to identify the iCa threshold needed to achieve adequate anticoagulation. Normal values for ACT were 90 s [2 standard deviations (SD) 72-109] in healthy children and 94 s (2 SD 75-113) in the uremic children. There was no statistically significant difference between the groups. In the children undergoing HD with RCA, the post-filter iCa level correlated with ACT (r = -0.94, p < 0.001). A post-filter iCa level of < or = 0.30 mmol/l reliably predicted an ACT >120 s. Our citrate protocol [citrate 3% rate (ml/h) approximately blood flow rate (ml/min) x 2] meets the established criteria with a high sensitivity. Based on these results, we conclude that the post-filter iCa level can be reliably used for the management of extracorporeal anticoagulation with citrate in pediatric HD. We recommend the application of our citrate prescription protocol in the setting of pediatric intermittent hemodialysis.
Assuntos
Anticoagulantes/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Cálcio/sangue , Ácido Cítrico/uso terapêutico , Monitoramento de Medicamentos/métodos , Falência Renal Crônica/sangue , Diálise Renal/métodos , Adolescente , Criança , Pré-Escolar , Feminino , Filtração , Humanos , Lactente , Recém-Nascido , Íons , Falência Renal Crônica/terapia , Masculino , Valor Preditivo dos Testes , Curva ROC , Valores de Referência , Estudos Retrospectivos , Uremia/sangue , Tempo de Coagulação do Sangue TotalRESUMO
Childhood hemolytic uremic syndrome (HUS) is most often caused by enterohemorrhagic Escherichia coli (EHEC). Due to severe hemolysis, red blood cell (RBC) transfusions are often necessary, and anemia is aggravated by low erythropoietin (EPO) levels caused by acute renal failure. In a single center, prospective study, we randomized ten children with EHEC-positive HUS into two therapeutic groups: one receiving EPO treatment (median age 2 years, age range 1-3 years) and the other receiving standard therapy (median age 2 years, age range 1-6 years). Red blood cell transfusions were performed when the hemoglobin level (Hb) fell below 5 mg/dl. The number of RBC transfusions was compared in both groups. The Hb level at admission was comparable between both groups (6.4 vs. 8.1 mg/dl, P > 0.05, t-test). However, children in the EPO group required a significantly lower mean number of RBCs than those in the non-EPO group (0.2 vs. 1.4, P < 0.04, t-test). Based on these results, we suggest that the early administration of EPO at the time of hemolytic anemia and beginning renal failure may attenuate renal anemia in children with EHEC-induced HUS and thereby reduce the number of RBC transfusions required. The results of this pilot study will have to be confirmed in a larger multicenter trial.
Assuntos
Anemia Hemolítica/terapia , Transfusão de Eritrócitos/estatística & dados numéricos , Eritropoetina/uso terapêutico , Síndrome Hemolítico-Urêmica/tratamento farmacológico , Anemia Hemolítica/sangue , Anemia Hemolítica/etiologia , Criança , Pré-Escolar , Síndrome Hemolítico-Urêmica/sangue , Síndrome Hemolítico-Urêmica/complicações , Humanos , Lactente , Projetos Piloto , Estudos Prospectivos , Proteínas RecombinantesAssuntos
Transplante de Rim , Seleção de Pacientes , Alocação de Recursos/métodos , Doadores de Tecidos/classificação , Obtenção de Tecidos e Órgãos/organização & administração , Adolescente , Adulto , Europa (Continente) , Feminino , Antígenos HLA/imunologia , Humanos , Modelos Logísticos , Masculino , Fatores de Tempo , Doadores de Tecidos/estatística & dados numéricos , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Listas de Espera , Adulto JovemRESUMO
It has been shown in adult kidney transplant recipients that a conversion from MMF to EC-MPS significantly reduced the GI related symptom burden. No such study exists on children with GI problems while receiving MMF therapy. Ten paediatric kidney transplant recipients (mean age 14.5 yr, s.d. 4.5) receiving triple immunosuppression (Cyclosporin A or Tacrolimus + MMF + Prednisolone) with severe GI symptoms were converted to an equimolar dose of EC-MPS. The GSRS was completed before and at four wk after the switch, and GFR was determined for a mean period of six months. Values were compared by the paired t-test. Mean GSRS improved significantly after the switch to EC-MPS in all but one patient, from 2.1 (s.d. 0.9) to 1.1 (s.d. 0.6). The differences could be found in all four subscales. Graft function did not change after conversion to EC-MPS. In children with moderate or severe GI symptoms while receiving MMF, conversion to EC-MPS led to significantly reduced GI symptoms.
Assuntos
Imunossupressores/uso terapêutico , Transplante de Rim/métodos , Ácido Micofenólico/análogos & derivados , Adolescente , Criança , Ciclosporina/administração & dosagem , Feminino , Gastroenteropatias/imunologia , Gastroenteropatias/patologia , Taxa de Filtração Glomerular , Humanos , Imunossupressores/farmacologia , Transplante de Rim/instrumentação , Masculino , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/química , Prednisolona/administração & dosagem , Comprimidos com Revestimento Entérico , Tacrolimo/administração & dosagemRESUMO
BACKGROUND: Cold ischemia and reperfusion during renal transplantation result in release of reactive oxygen species. The aim of this study is to examine whether cold storage induced cell injury can be ameliorated by adding flavonoids directly to preservation solutions. METHODS: Cultured renal tubular epithelial cells (LLC-PK1) were stored in University of Wisconsin (UW) or Euro-Collins (EC) solution at 4 degrees C for 20 hours. Preservation solutions were supplemented with various flavonoids. After rewarming, structural and metabolic cell integrity was measured by lactate dehydrogenase (LDH) release and MTT-test, and lipid peroxidation was assessed from generation of thiobarbituric acid-reactive substances (TBARS). RESULTS: Twenty hours of cold storage resulted in a substantial loss of cell viability in both preservation solutions (in EC: LDH release 92.4+/-2.7%; MTT-test 0.5+/-0.7%). Addition of luteolin, quercetin, kempferol, fisetin, myricetin, morin, catechin, and silibinin significantly reduced cell injury (for luteolin in EC: LDH release 2.4+/-1.6%; MTT-test 110.3+/-10.4%, P<0.01; TBARS-production (related to cold stored control cells) 8.9+/-2.6%). No cytoprotection was found for apigenin, naringenin, and rutin. Protective potency of flavonoids depends on number of hydroxyl-substituents and lipophilicity of the diphenylpyran compounds. CONCLUSION: Cold storage induced injury of renal tubular cells was substantially ameliorated by adding selected flavonoids directly to preservation solutions.
Assuntos
Crioprotetores , Flavonoides , Túbulos Renais Proximais/citologia , Soluções para Preservação de Órgãos , Preservação de Órgãos/métodos , Adenosina , Alopurinol , Animais , Sobrevivência Celular/efeitos dos fármacos , Temperatura Baixa , Crioprotetores/administração & dosagem , Flavonoides/administração & dosagem , Flavonoides/química , Glutationa , Soluções Hipertônicas , Técnicas In Vitro , Insulina , Transplante de Rim , Túbulos Renais Proximais/metabolismo , L-Lactato Desidrogenase/metabolismo , Células LLC-PK1 , Peroxidação de Lipídeos/efeitos dos fármacos , Luteolina/administração & dosagem , Estrutura Molecular , Quercetina/administração & dosagem , Rafinose , Traumatismo por Reperfusão/prevenção & controle , SuínosAssuntos
Trato Gastrointestinal/efeitos dos fármacos , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/toxicidade , Adulto , Área Sob a Curva , Criança , Rejeição de Enxerto , Humanos , Sistema Imunitário , Imunossupressores/uso terapêutico , Adesão à Medicação , Ácido Micofenólico/economia , Ácido Micofenólico/uso terapêutico , Transplante de Órgãos , Ensaios Clínicos Controlados Aleatórios como Assunto , Risco , Comprimidos com Revestimento EntéricoRESUMO
BACKGROUND: Thrombotic microangiopathy (TMA) in renal transplants (rTx-TMA) is a serious complication and is usually either recurrent TMA (RecTMA) due to humoral rejection (HR-TMA) or due to calcineurin inhibitor toxicity (CNI-TMA). Although the triggers are known, our knowledge about the thrombogenic transcriptome changes in the microvessels is rudimentary. METHODS: We examined the expression of several prothrombotic and antithrombotic genes in 25 biopsies with rTx-TMA (6 RecTMA, 9 HR-TMA, and 10 CNI-TMA) and 8 controls. RNA from microdissected glomeruli of paraffin-embedded tissue was isolated and mRNA transcripts were quantified with real-time polymerase chain reaction after preamplification. Results were correlated with clinicopathologic parameters. RESULTS: Glomerular mRNA expression of KLF2, KLF4, and tPA was lower and that of PAI-1 was higher in rTx-TMA than in the controls. Glomerular mRNA expression of KLF2 and KLF4 correlated with that of tPA and inversely with that of PAI-1 in rTx-TMA. The mRNA expression of complement regulators CD46 and CD59 were higher in rTx-TMA than in the controls. Only in HR-TMA were glomerular ADAMTS13 and CD55 down-regulated. CONCLUSIONS: The glomerular capillary bed seems to contribute to all subtypes of rTx-TMA by down-regulation of the endothelial transcription factors KLF2 and KLF4, indicating dedifferentiation with subsequent up-regulation of PAI-1 and down-regulation of tPA, resulting in inhibition of local fibrinolysis. Decreased glomerular expression of ADAMTS13 and CD55 could be an additional pathway toward microthrombosis exclusively in HR-TMA.