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BACKGROUND: Continuous kidney replacement therapy (CKRT) has recently become the preferred kidney replacement modality for children with acute kidney injury (AKI). We hypothesise that CKRT technical parameters and treatment settings in addition to the clinical characteristics of patients may influence the circuit lifetime in children. METHODS: The study involved children included in the EurAKId registry (NCT02960867), who underwent CKRT treatment. We analysed patient characteristics and CKRT parameters. The primary end point was mean circuit lifetime (MCL). Secondary end points were number of elective circuit changes and occurrence of dialysis-related complications. RESULTS: The analysis was composed of 247 children who underwent 37,562 h of CKRT (median 78, IQR 37-165 h per patient). A total of 1357 circuits were utilised (3, IQR 2-6 per patient). MCL was longer in regional citrate anticoagulation (RCA), compared to heparin (HA) and no anticoagulation (NA) (42, IQR 32-58 h; 24, IQR 14-34 h; 18, IQR 12-24 h, respectively, p < 0.001). RCA was associated with longer MCL regardless of the patient's age or dialyser surface. In multivariate analysis, MCL correlated with dialyser surface area (beta = 0.14, p = 0.016), left internal jugular vein vascular access site (beta = -0.37, p = 0.027), and the use of HA (beta = -0.14, p = 0.038) or NA (beta = -0.37, p < 0.001) vs. RCA. RCA was associated with the highest ratio of elective circuit changes and the lowest incidence of complications. CONCLUSION: Anticoagulation modality, dialyser surface, and vascular access site influence MCL. RCA should be considered when choosing first-line anticoagulation for CKRT in children. Further efforts should focus on developing guidelines and clinical practice recommendations for paediatric CKRT.
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Background: Despite significant cardiovascular (CV) morbidity in children on dialysis and after kidney transplantation, data on the evolution of CV damage in children with chronic kidney disease (CKD) approaching kidney replacement therapy (KRT) is unknown. Methods: The burden, progression, and predictors of CV damage before KRT onset were explored in two prospective multicenter cohorts from Europe and Canada: Cardiovascular Comorbidity in Children with CKD (4C) and Haemodiafiltration, Heart and Height (3H) studies, conducted from 2009-19 and 2013-16, respectively. CV damage and risk factors were evaluated (i) cross sectionally at KRT-start (n = 248), and (ii) longitudinally over the 2-years preceding KRT start (n = 157; 331 patient-visits). Longitudinal analyses with mixed-effects models estimated associations of modifiable CV risk factors with change in carotid intima-media thickness (cIMT) standard deviation score (SDS), pulse wave velocity (PWV-SDS), left ventricular (LV) mass and systolic dysfunction. Findings: 248 patients, age 14.3 (12.2, 16.2) years were evaluated at median 35 (28-114) days before KRT start. Elevated cIMT-SDS and PWV-SDS were present in 43% and 25%, and LV hypertrophy and systolic dysfunction in 49% and 33%. Aortic stiffness and LV hypertrophy significantly increased, especially in the year before KRT start (adjusted odds ratio, OR 0.33, P = 0.002 and OR 0.54, P = 0.01, respectively). 79% of children had >3 modifiable CV risk factors at KRT onset. Diastolic BP and BMI were strongly associated with a linear increase in all CV measures. After controlling for CV risk factors, the time to KRT onset no longer predicted the burden of CV damage. Interpretation: This comprehensive CV evaluation shows the progressive accrual of modifiable risk factors and a high burden of CV damage in the years preceding KRT onset. CV damage in the pre-KRT period is preventable. Funding: Supported by EU4Health Programme (101085068) and Kidney Research UK (RP39/2013).
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BACKGROUND: Dyslipidemia is an important and modifiable risk factor for CVD in children with CKD. METHODS: In a cross-sectional study of baseline serum lipid levels in a large prospective cohort study of children with stage 3-5 (predialysis) CKD, frequencies of abnormal lipid levels and types of dyslipidemia were analyzed in the entire cohort and in subpopulations defined by fasting status or by the presence of nephrotic range proteinuria. Associated clinical and laboratory characteristics were determined by multivariable linear regression analysis. RESULTS: A total of 681 patients aged 12.2 ± 3.3 years with a mean eGFR of 26.9 ± 11.6 ml/min/1.73 m2 were included. Kidney diagnosis was classified as CAKUT in 69%, glomerulopathy in 8.4%, and other disorders in 22.6% of patients. Nephrotic range proteinuria (defined by a urinary albumin/creatinine ratio > 1.1 g/g) was present in 26.9%. Dyslipidemia was found in 71.8%, and high triglyceride (TG) levels were the most common abnormality (54.7%). Fasting status (38.9%) had no effect on dyslipidemia status. Except for a significant increase in TG in more advanced CKD, lipid levels and frequencies of dyslipidemia were not significantly different between CKD stages. Hypertriglyceridemia was associated with younger age, lower eGFR, shorter duration of CKD, higher body mass index (BMI-SDS), lower serum albumin, and higher diastolic blood pressure. CONCLUSIONS: Dyslipidemia involving all lipid fractions, but mainly TG, is present in the majority of patients with CKD irrespective of CKD stage or fasting status and is significantly associated with other cardiovascular risk factors.
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Doenças Cardiovasculares , Dislipidemias , Taxa de Filtração Glomerular , Insuficiência Renal Crônica , Humanos , Masculino , Dislipidemias/epidemiologia , Dislipidemias/sangue , Feminino , Criança , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Estudos Transversais , Adolescente , Estudos Prospectivos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Fatores de Risco , Comorbidade , Lipídeos/sangue , Proteinúria/epidemiologia , Proteinúria/etiologia , Triglicerídeos/sangueRESUMO
BACKGROUND: One of the most common bacterial infections in childhood is urinary tract infection (UTI). Toll-like receptors (TLRs) contribute to immune response against UTI recognizing specific pathogenic agents. Our aim was to determine whether soluble TLR4 (sTLR4), soluble TLR5 (sTLR5) and interleukin 8 (IL-8) can be used as biomarkers to diagnose UTI. We also aimed to reveal the relationship between urine Heat Shock Protein 70 (uHSP70) and those biomarkers investigated in this study. METHODS: A total of 802 children from 37 centers participated in the study. The participants (n = 282) who did not meet the inclusion criteria were excluded from the study. The remaining 520 children, including 191 patients with UTI, 178 patients with non-UTI infections, 50 children with contaminated urine samples, 26 participants with asymptomatic bacteriuria and 75 healthy controls were included in the study. Urine and serum levels of sTLR4, sTLR5 and IL-8 were measured at presentation in all patients and after antibiotic treatment in patients with UTI. RESULTS: Urine sTLR4 was higher in the UTI group than in the other groups. UTI may be predicted using 1.28 ng/mL as cut-off for urine sTLR4 with 68% sensitivity and 65% specificity (AUC = 0.682). In the UTI group, urine sTLR4 levels were significantly higher in pyelonephritis than in cystitis (p < 0.0001). Post-treatment urine sTLR4 levels in the UTI group were significantly lower than pre-treatment values (p < 0.0001). CONCLUSIONS: Urine sTLR4 may be used as a useful biomarker in predicting UTI and subsequent pyelonephritis in children with UTI. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Pielonefrite , Infecções Urinárias , Criança , Humanos , Interleucina-8/urina , Receptor 4 Toll-Like , Infecções Urinárias/diagnóstico , Infecções Urinárias/urina , Pielonefrite/diagnóstico , BiomarcadoresRESUMO
OBJECTIVE: Immunoglobulin-A vasculitis (IgAV) is an inflammatory disease that affects small blood vessels. This study was performed to identify an association between protein tyrosine phosphatase non-receptor type 22 (PTPN22) + 788G > A (rs33996649), transforming growth factor-beta (TGF-ß) -509C > T (rs18004069), interleukin 1-beta (IL-1ß) -511C > T (rs16944), interleukin 5 (IL-5) -746C/T (rs2069812), and angiotensin-converting enzyme (ACE) I/D (rs4646994) gene polymorphisms, susceptibility to IgAV, as well as the mRNA levels of IL-1ß, IL-1ß, and TGF-ß. METHOD: A total of 53 patients with IgAV and 50 healthy controls were enrolled. PTPN22, TGF-ß, IL-1ß, ACE gene polymorphisms, ACE gene I/D polymorphisms, and mRNA expression levels were analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, allele-specific PCR, and real-time PCR with TaqMan kits, respectively. RESULTS: PTPN22, TGF-ß, IL-1ß, IL-5, and ACE variants showed no genotype or allele differences between patients with IgAV and controls. Increased levels of IL-1ß and TGF-ß mRNA expressions were observed in patients with IgAV (p < 0.001). Patients with the IL-1ß AG genotype showed significantly increased amounts of arthritis than patients with non-AG (p = 0.004). Age at disease onset was found to be significantly different in patients with IgAV according to the presence of TGF-ß TT genotype (p = 0.047). CONCLUSION: Polymorphisms in PTPN22, TGF-ß, IL-5, IL-1ß, and ACE genes are unlikely to confer susceptibility to IgAV. However, the presence of the AG genotype of IL-1ß is associated with susceptibility to IgAV-related arthritis. This is the first study to report a significant increase in serum mRNA levels of IL-1ß and TGF-ß in IgAV patients, supporting a susceptibility to IgAV in childhood.
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Artrite , Vasculite por IgA , Criança , Humanos , Interleucina-5/genética , Vasculite por IgA/genética , Fator de Crescimento Transformador beta/genética , Peptidil Dipeptidase A/genética , Polimorfismo Genético/genética , Genótipo , Reação em Cadeia da Polimerase em Tempo Real , RNA Mensageiro/genética , Expressão Gênica , Predisposição Genética para Doença , Frequência do Gene/genética , Estudos de Casos e Controles , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
BACKGROUND: Kidney transplantation is the predominant treatment option in patients with end-stage renal disease. The aim of this study was to evaluate the effect of the presence of a psychiatric disorder on the quality of life in children and adolescents after kidney transplantation. METHODS: A total of 43 patients aged 6 to 18 years were included in the study. All participants and their parents were asked to complete the Pediatric Quality of Life Inventory (PedsQL), and families only, the Strengths and Challenges Questionnaire. Psychiatric symptoms and disorders of the patients were evaluated according to the Schedule for Mood Disorders and Schizophrenia for School-Age Children/Now and Lifetime Turkish Version. Patients were divided into 2 groups according to psychiatric symptoms and disorders. RESULTS: The most common psychiatric disorder was attention deficit and hyperactivity disorder (26%). The questionnaires filled out by the patients revealed a lower Total PedsQL Score (P = .003), PedsQL Physical Functionality Score (P = .019), and PedsQL Social Functioning Score (P = .016) in patients with psychiatric disorders. When the parents filled out the questionnaires, the Total PedsQL Score was similar in both groups. The PedsQL Emotional Functionality Score (P = .001) and PedsQL School Functionality Score (P = .004) were significantly lower in patients with psychiatric disorders. The Strengths and Difficulties Questionnaire revealed significantly higher total (P = .014) and hyperactivity/inattention subscale scores (P = .001) in those with a psychiatric disorder. CONCLUSIONS: Psychiatric disorders in kidney transplant patients adversely affect the quality of life.
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Transtorno do Deficit de Atenção com Hiperatividade , Falência Renal Crônica , Transplante de Rim , Humanos , Criança , Adolescente , Qualidade de Vida/psicologia , Transplante de Rim/efeitos adversos , Bem-Estar Psicológico , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), systemic immune-inflammation index (SII = N × P/L), and neutrophil percentage-albumin ratio (NPAR) have become accepted markers of inflammation in recent years. These indices are used as indicators of disease activity, mortality, and morbidity in many diseases. This study evaluated the relationship between inflammatory indices and graft function in pediatric kidney transplant recipients. METHODS: Medical records of pediatric patients who underwent kidney transplantation at Ege University between 1995 and 2020 were reviewed retrospectively. Demographic, clinical, and laboratory data were recorded during the third month, first year, and fifth year of transplantation and at the last visit. RESULTS: The median age of the 119 patients (60 boys/59 girls) at the time of transplantation was 154 months, and the median follow-up period was 101 months. According to Spearman correlation analysis, patients' final creatinine levels were positively correlated with NLR (r = 0.319), PLR (r = 0.219), SII (r = 0.214), and NPAR (r = 0.347) of the last visit; final estimate glomerular filtration rate levels were negatively correlated with NLR (P = .010, r = -0.250) and NPAR (P = .004, r = -0.277). The median NPAR of the patients with chronic allograft dysfunction at the last visit was found to be statistically significantly higher than without (P = .032). CONCLUSION: NLR, PLR, SII, and NPAR values are correlated with creatinine levels after 5 years of kidney transplantation. The NPAR and final creatinine levels had the highest correlation coefficient among these inflammatory markers. These results suggest that inflammatory markers, especially NPAR, may be a candidate to be an indicator of ongoing inflammation in the graft.
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Transplante de Rim , Masculino , Feminino , Humanos , Criança , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Creatinina , Inflamação , Linfócitos , Neutrófilos , AlbuminasRESUMO
BACKGROUND: The negative effects of pretransplant obesity and post-transplant body mass index (BMI) increase on graft survival have been reported in recent years. The aim of this study is to evaluate the effects of BMI changes on post-transplant graft function, lipid profile, and blood pressure. METHODS: The study included 133 pediatric patients transplanted between 1994 and 2019 in Ege University. BMI Z-scores (BMIZs) were calculated according to age and sex before and after transplantation using the World Health Organization criteria. Patients with BMIZs >+1 standard deviation (SD) were defined as overweight, and those with BMIZs >+2 SD were defined as obese: Group 1: Obese or overweight before transplantation; Group 2: Thin or normal weight before and 2 years after transplantation; and Group 3: Thin or normal weight before transplantation and obese or overweight 2 years after transplantation. RESULTS: At the time of transplantation 8% of the patients were overweight, and 1% were obese. Overweight and obesity statistically significantly increased (31.6%) 2 years after renal transplantation (P = .001). Obese and overweight patients have lower high-density lipoprotein levels and were younger at the time of transplantation. Graft functions, lipid levels, and blood glucose levels of the groups were similar (P > .05). The only significant difference between the groups was that Group 1 patients were younger than Group 2. CONCLUSIONS: Obesity develops at a significant rate in pediatric patients after renal transplantation. In this study, we could not demonstrate negative effects of obesity and being overweight in terms of post-transplant graft function, lipid profile, blood glucose, and blood pressure.
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Transplante de Rim , Humanos , Criança , Transplante de Rim/efeitos adversos , Sobrepeso , Índice de Massa Corporal , Glicemia , Obesidade , Lipídeos , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: The accuracy of conventional urinalysis in diagnosing urinary tract infection (UTI) in children is limited, leading to unnecessary antibiotic exposure in a large fraction of patients. Urinary heat shock protein 70 (uHSP70) is a novel marker of acute urinary tract inflammation. We explored the added value of uHSP70 in discriminating UTI from other infections and conditions confused with UTI. METHODS: A total of 802 children from 37 pediatric centers in seven countries participated in the study. Patients diagnosed with UTI (n = 191), non-UTI infections (n = 178), contaminated urine samples (n = 50), asymptomatic bacteriuria (n = 26), and healthy controls (n = 75) were enrolled. Urine and serum levels of HSP70 were measured at presentation in all patients and after resolution of the infection in patients with confirmed UTI. RESULTS: Urinary (u)HSP70 was selectively elevated in children with UTI as compared to all other conditions (p < 0.0001). uHSP70 predicted UTI with 89% sensitivity and 82% specificity (AUC = 0.934). Among the 265 patients with suspected UTI, the uHSP70 > 48 ng/mL criterion identified the 172 children with subsequently confirmed UTI with 90% sensitivity and 82% specificity (AUC = 0.862), exceeding the individual diagnostic accuracy of leukocyturia, nitrite, and leukocyte esterase positivity. uHSP70 had completely normalized by the end of antibiotic therapy in the UTI patients. Serum HSP70 was not predictive. CONCLUSIONS: Urine HSP70 is a novel non-invasive marker of UTI that improves the diagnostic accuracy of conventional urinalysis. We estimate that rapid urine HSP70 screening could spare empiric antibiotic administration in up to 80% of children with suspected UTI. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Infecções Urinárias , Sistema Urinário , Humanos , Criança , Infecções Urinárias/tratamento farmacológico , Urinálise , Antibacterianos/uso terapêutico , Proteínas de Choque Térmico HSP70 , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: The "HDF-Heart-Height" study showed that haemodiafiltration (HDF) is associated with improved growth compared to conventional haemodialysis (HD). We report a post-hoc analysis of this study assessing the effect of extracorporeal dialysis therapies on nutritional indices. METHODS: 107 children were included in the baseline cross-sectional analysis, of whom 79 (43 HD, 36 HDF) completed the 12-month follow-up. Height (Ht), optimal 'dry' weight (Wt), and body mass index (BMI) standard deviations scores (SDS), waist-to-hip ratio, des-acyl ghrelin (DAG), adiponectin, leptin, insulin-like growth factor-1 (IGF-1)-SDS and insulin were measured. RESULTS: The levels of nutritional indices were comparable between HDF and HD patients at baseline and 12-month. On univariable analyses Wt-SDS positively correlated with leptin and IGF-1-SDS, and negatively with DAG, while Ht-SDS of the overall cohort positively correlated with IGF1-SDS and inversely with DAG and adiponectin. On multivariable analyses, higher 12-month Ht-SDS was inversely associated with baseline DAG (beta = -0.13 per 500 higher; 95%CI -0.22, -0.04; P = .004). Higher Wt-SDS at 12-month was positively associated with HDF modality (beta = 0.47 vs HD; 95%CI 0.12-0.83; P = .01) and inversely with baseline DAG (beta = -0.18 per 500 higher; 95%CI -0.32, -0.05; P = .006). Growth Hormone (GH) treated patients receiving HDF had higher annualized increase in Ht SDS compared to those on HD. CONCLUSIONS: In children on HD and HDF both Wt- and Ht-SDS independently correlated with lower baseline levels of the anorexygenic hormone DAG. HDF may attenuate the resistance to GH, but further studies are required to examine the mechanisms linking HDF to improved growth.
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Hemodiafiltração , Falência Renal Crônica , Humanos , Criança , Hemodiafiltração/efeitos adversos , Fator de Crescimento Insulin-Like I , Leptina , Estudos Transversais , Adiponectina , Diálise Renal/efeitos adversos , Peso Corporal , Falência Renal Crônica/terapia , Falência Renal Crônica/etiologiaRESUMO
INTRODUCTION: We searched for risk factors of cardiovascular assessment among children on dialysis. METHODS: This is a cross-sectional study of cardiovascular assessment of all patients on dialysis at Ege University Children's Hospital. Pediatric patients between the ages of 6 and 21 who were on HD and peritoneal dialysis treatment were included in the study. Cardiovascular evaluation included left ventricular mass index (LVMI), pulse wave velocity (PWV), and carotid intima-media thickness (cIMT) measurements. RESULTS: Nineteen patients were included in this study. The LDL had a correlation with the cIMT z-score, but not to PWVz-score. Binary Logistic regression analysis found that only LDL was significantly associated to increased cIMT. CONCLUSION: This study reports an association between high LDL and high BP increased cIMT on dialyzed children. Strategies to reduce LDL and BP in dialysis patients may prevent vasculopathy and long-term cardiovascular complications.
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Doenças Cardiovasculares , Diálise Renal , Adolescente , Criança , Humanos , Adulto Jovem , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/epidemiologia , Espessura Intima-Media Carotídea , Estudos Transversais , Lipoproteínas LDL , Análise de Onda de Pulso , Diálise Renal/efeitos adversos , Fatores de RiscoRESUMO
BACKGROUND: Acute kidney injury (AKI), particularly that requiring dialysis, is a severe complication in hospitalized children that is associated with high morbidity and mortality. A prospective European AKI registry (EurAKId registry, NCT02960867) was created to describe the epidemiology and outcomes of paediatric patients treated with acute dialysis. METHODS: Children were recruited who were between 0 and 18 years of age and were treated both in and outside the paediatric intensive care unit (PICU) with peritoneal dialysis (PD), haemodialysis (HD) or continuous kidney replacement therapy (CKRT) for AKI or metabolic derangement, fluid overload (FO), sepsis or respiratory distress. Five age groups and 12 categories of primary diseases were defined. RESULTS: Data on 340 patients were analysed, of whom 86% received dialysis for AKI and 14% for reasons other than AKI. Boys accounted for 60% of the patients. Illness severity was greater in children with cardiac and haematologic diseases than those with kidney diseases. Most patients received dialysis in the PICU (84%). The most frequently used dialysis modality was CKRT (64%), followed by PD (14%) and HD (14%). The overall survival rate was 65%. Survival was significantly lower in children with three comorbidities than in children with no comorbidities (41% and 83%; P < 0.001). CONCLUSIONS: The EurAKId registry is the first prospective registry considering paediatric acute kidney replacement therapies (KRTs) in both critical and non-critical care settings, focusing on the three dialysis modalities in Europe. The clinical indications for KRT have expanded; our population was characterized by critically ill patients, primarily boys, who frequently received dialysis in the PICU with CKRT.
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Injúria Renal Aguda , Terapia de Substituição Renal , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Criança , Estado Terminal , Feminino , Humanos , Masculino , Morbidade , Sistema de Registros , Diálise Renal , Terapia de Substituição Renal/efeitos adversosRESUMO
BACKGROUND: Patients on dialysis have a high burden of bone-related comorbidities, including fractures. We report a post hoc analysis of the prospective cohort study HDF, Hearts and Heights (3H) to determine the prevalence and risk factors for chronic kidney disease-related bone disease in children on hemodiafiltration (HDF) and conventional hemodialysis (HD). METHODS: The baseline cross-sectional analysis included 144 children, of which 103 (61 HD, 42 HDF) completed 12-month follow-up. Circulating biomarkers of bone formation and resorption, inflammatory markers, fibroblast growth factor-23, and klotho were measured. RESULTS: Inflammatory markers interleukin-6, tumor necrosis factor-α, and high-sensitivity C-reactive protein were lower in HDF than in HD cohorts at baseline and at 12 months (P < .001). Concentrations of bone formation (bone-specific alkaline phosphatase) and resorption (tartrate-resistant acid phosphatase 5b) markers were comparable between cohorts at baseline, but after 12-months the bone-specific alkaline phosphatase/tartrate-resistant acid phosphatase 5b ratio increased in HDF (P = .004) and was unchanged in HD (P = .44). On adjusted analysis, the bone-specific alkaline phosphatase/tartrate-resistant acid phosphatase 5b ratio was 2.66-fold lower (95% confidence interval, -3.91 to -1.41; P < .0001) in HD compared with HDF. Fibroblast growth factor-23 was comparable between groups at baseline (P = .52) but increased in HD (P < .0001) and remained unchanged in HDF (P = .34) at 12 months. Klotho levels were similar between groups and unchanged during follow-up. The fibroblast growth factor-23/klotho ratio was 3.86-fold higher (95% confidence interval, 2.15-6.93; P < .0001) after 12 months of HD compared with HDF. CONCLUSION: Children on HDF have an attenuated inflammatory profile, increased bone formation, and lower fibroblast growth factor-23/klotho ratios compared with those on HD. Long-term studies are required to determine the effects of an improved bone biomarker profile on fracture risk and cardiovascular health.
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BACKGROUND: Hypertension is prevalent in children on dialysis and associated with cardiovascular disease. We studied the blood pressure (BP) trends and the evolution of BP over 1 year in children on conventional hemodialysis (HD) vs. hemodiafiltration (HDF). METHODS: This is a post hoc analysis of the "3H - HDF-Hearts-Height" dataset, a multicenter, parallel-arm observational study. Seventy-eight children on HD and 55 on HDF who had three 24-h ambulatory BP monitoring (ABPM) measures over 1 year were included. Mean arterial pressure (MAP) was calculated and hypertension defined as 24-h MAP standard deviation score (SDS) ≥95th percentile. RESULTS: Poor agreement between pre-dialysis systolic BP-SDS and 24-h MAP was found (mean difference - 0.6; 95% limits of agreement -4.9-3.8). At baseline, 82% on HD and 44% on HDF were hypertensive, with uncontrolled hypertension in 88% vs. 25% respectively; p < 0.001. At 12 months, children on HDF had consistently lower MAP-SDS compared to those on HD (p < 0.001). Over 1-year follow-up, the HD group had mean MAP-SDS increase of +0.98 (95%CI 0.77-1.20; p < 0.0001), whereas the HDF group had a non-significant increase of +0.15 (95%CI -0.10-0.40; p = 0.23). Significant predictors of MAP-SDS were dialysis modality (ß = +0.83 [95%CI +0.51 - +1.15] HD vs. HDF, p < 0.0001) and higher inter-dialytic-weight-gain (IDWG)% (ß = 0.13 [95%CI 0.06-0.19]; p = 0.0003). CONCLUSIONS: Children on HD had a significant and sustained increase in BP over 1 year compared to a stable BP in those on HDF, despite an equivalent dialysis dose. Higher IDWG% was associated with higher 24-h MAP-SDS in both groups.
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Hemodiafiltração , Falência Renal Crônica , Pressão Sanguínea , Criança , Humanos , Hipertensão/terapia , Falência Renal Crônica/terapia , Diálise Renal/efeitos adversos , Aumento de PesoRESUMO
BACKGROUND: Uraemic cardiac remodelling is associated with vitamin D and Klotho deficiency, elevated fibroblast growth factor 23 (FGF23) and activation of the renin-angiotensin system (RAS). The cardioprotective properties of active vitamin D analogues in this setting are unclear. METHODS: In rats with 5/6 nephrectomy (5/6Nx) treated with calcitriol, the cardiac phenotype and local RAS activation were investigated compared with controls. A nested case-control study was performed within the Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) study, including children with chronic kidney disease (CKD) Stages 3-5 [estimated glomerular filtration rate (eGFR) 25 mL/min/1.73 m2] treated with and without active vitamin D. Echocardiograms, plasma FGF23 and soluble Klotho (sKlotho) were assessed at baseline and after 9 months. RESULTS: In rats with 5/6Nx, left ventricular (LV) hypertrophy, LV fibrosis and upregulated cardiac RAS were dose-dependently attenuated by calcitriol. Calcitriol further stimulated FGF23 synthesis in bone but not in the heart, and normalized suppressed renal Klotho expression. In the 4C study cohort, treatment over a mean period of 9 months with active vitamin D was associated with increased FGF23 and phosphate and decreased sKlotho and eGFR compared with vitamin D naïve controls, whereas LV mass index did not differ between groups. CONCLUSIONS: Active vitamin D ameliorates cardiac remodelling and normalizes renal Klotho expression in 5/6Nx rats but does not improve the cardiac phenotype in children with CKD Stages 3-5. This discrepancy may be due to further enhancement of circulating FGF23 and faster progression of CKD associated with reduced sKlotho and higher serum phosphate in vitamin D-treated patients.
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Calcitriol/farmacologia , Hipertrofia Ventricular Esquerda/prevenção & controle , Insuficiência Renal Crônica/fisiopatologia , Uremia/complicações , Vitaminas/farmacologia , Animais , Estudos de Casos e Controles , Criança , Feminino , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/metabolismo , Taxa de Filtração Glomerular , Glucuronidase/metabolismo , Humanos , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/metabolismo , Hipertrofia Ventricular Esquerda/patologia , Proteínas Klotho , Masculino , Ratos , Ratos Sprague-Dawley , Sistema Renina-AngiotensinaRESUMO
The uremic toxins indoxyl sulfate (IS) and p-cresyl sulfate (pCS) accumulate in patients with chronic kidney disease (CKD) as a consequence of altered gut microbiota metabolism and a decline in renal excretion. Despite of solid experimental evidence for nephrotoxic effects, the impact of uremic toxins on the progression of CKD has not been investigated in representative patient cohorts. In this analysis, IS and pCS serum concentrations were measured in 604 pediatric participants (mean eGFR of 27 ± 11 ml/min/1.73m2) at enrolment into the prospective Cardiovascular Comorbidity in Children with CKD study. Associations with progression of CKD were analyzed by Kaplan-Meier analyses and Cox proportional hazard models. During a median follow up time of 2.2 years (IQR 4.3-0.8 years), the composite renal survival endpoint, defined as 50% loss of eGFR, or eGFR <10ml/min/1.73m2 or start of renal replacement therapy, was reached by 360 patients (60%). Median survival time was shorter in patients with IS and pCS levels in the highest versus lowest quartile for both IS (1.5 years, 95%CI [1.1,2.0] versus 6.0 years, 95%CI [5.0,8.4]) and pCS (1.8 years, 95%CI [1.5,2.8] versus 4.4 years, 95%CI [3.4,6.0]). Multivariable Cox regression disclosed a significant association of IS, but not pCS, with renal survival, which was independent of other risk factors including baseline eGFR, proteinuria and blood pressure. In this exploratory analysis we provide the first data showing a significant association of IS, but not pCS serum concentrations with the progression of CKD in children, independent of other known risk factors. In the absence of comorbidities, which interfere with serum levels of uremic toxins, such as diabetes, obesity and metabolic syndrome, these results highlight the important role of uremic toxins and accentuate the unmet need of effective elimination strategies to lower the uremic toxin burden and abate progression of CKD.
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Biomarcadores/sangue , Indicã/sangue , Insuficiência Renal Crônica/sangue , Adolescente , Criança , Cresóis/sangue , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Modelos de Riscos Proporcionais , Estudos Prospectivos , Insuficiência Renal Crônica/mortalidade , Ésteres do Ácido Sulfúrico/sangue , Análise de SobrevidaRESUMO
INTRODUCTION: In this study,we investigated the presence of cytomegalovirus (CMV) infection in kidney transplanted children and its effect on kidney dysfunction. MATERIAL AND METHODS: One hundred thirty-five pediatric renal transplant patients were included in this study. The presence of CMV infection, CMV risk status, and other clinical features of the patients were evaluated retrospectively. RESULTS: Fifty-three percent of all patients and 68.8% of patients with CMV were male. The mean age was 12 years in all patients and CMV groups. According to the CMV risk classification, 40.9% of the patients with CMV infection/disease were in the high-risk group (CMV D+R-). In CMV risk groups, the presence of CMV infection/disease was similar. Cold ischemia time, male sex (patients and donors), deceased donor, higher HLA-mismatches, and cumulative antithymocyte globulin dose were found as risk factors for CMV infection/disease. Acute rejection/graft failure was observed in 27% of all patients. CMV infection has no effect on rejection/graft failure and survival. DISCUSSION: The frequency and risk factors of CMV in renal transplant children in our study were consistent with the literature. CONCLUSIONS: CMV infection was found in one-fifth of our patients and the majority (71.9%) of them developed infection in the first 6 months. In one-third of our patients acute rejection/graft failure was observed. There was no effect of CMV infection on rejection/graft failure and survival in pediatric patients with proper and effective treatment.
Assuntos
Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/imunologia , Hospedeiro Imunocomprometido , Transplante de Rim , Complicações Pós-Operatórias/virologia , Antivirais/uso terapêutico , Criança , Citomegalovirus/imunologia , Infecções por Citomegalovirus/tratamento farmacológico , Feminino , Rejeição de Enxerto/virologia , Humanos , Masculino , Complicações Pós-Operatórias/imunologia , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
Rapidly progressive glomerulonephritis (RPGN) is rare syndrome in children, characterized by clinical features of glomerulonephritis and rapid loss of renal function, and is associated with crescentic glomerulonephritis. Primary membranous nephropathy (MN) is an immune-complex-mediated cause of the adult nephrotic syndrome but occurs less frequently in children. RPGN is rarely observed in adults with primary MN. In this article, we report a case of MN, which developed during long-term follow-up of previously treated RPGN. Our case may be the first to demonstrate primary MN and crescentic glomerulonephritis in a child. We would like to underline the importance of not dropping the long-term follow-up of cases with primary RPGN (not accompanied by other glomerulonephritis and vasculitis symptoms) who had improved with treatment.
Assuntos
Glomerulonefrite Membranosa/patologia , Glomerulonefrite/patologia , Glomérulos Renais/patologia , Corticosteroides/uso terapêutico , Progressão da Doença , Glomerulonefrite/tratamento farmacológico , Glomerulonefrite/fisiopatologia , Glomerulonefrite Membranosa/tratamento farmacológico , Glomerulonefrite Membranosa/fisiopatologia , Humanos , Imunossupressores/uso terapêutico , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/fisiopatologia , Masculino , Indução de Remissão , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Cardiovascular disease is the leading cause of death in children with chronic kidney disease (CKD). Serum levels of gut-derived uremic toxins increase with deterioration of kidney function and are associated with cardiac comorbidities in adult CKD patients. METHODS: Indoxyl sulfate (IS) and p-cresyl sulfate (pCS) were measured by high-performance liquid chromatography in serum of children participating in the Cardiovascular Comorbidity in Children with CKD (4C) Study. Results were correlated with measurements of the carotid intima-media thickness (cIMT), central pulse wave velocity (PWV), and left ventricular mass index (LVMI) in children aged 6-17 years with initial eGFR of 10-60 ml/min per 1.73 m2. RESULTS: The median serum levels of total IS and of pCS, measured in 609 patients, were 5.3 µmol/l (8.7) and 17.0 µmol/l (21.6), respectively. In a multivariable regression model, IS and pCS showed significant positive associations with urea and negative associations with eGFR and uric acid. Furthermore, positive associations of pCS with age, serum albumin, and non-Mediterranean residency and a negative association with glomerular disease were observed. By multivariable regression analysis, only IS was significantly associated with a higher cIMT SDS at baseline and progression of PWV SDS within 12 months, independent of other risk factors. CONCLUSIONS: Serum levels of gut-derived uremic toxins IS and pCS correlated inversely with eGFR in children. Only IS was significantly associated with surrogate markers of cardiovascular disease in this large pediatric CKD cohort.
Assuntos
Indicã/sangue , Insuficiência Renal Crônica/sangue , Adolescente , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Criança , Cresóis/sangue , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Fenótipo , Insuficiência Renal Crônica/complicações , Ésteres do Ácido Sulfúrico/sangueRESUMO
INTRODUCTION: and Aim. End-stage renal disease owing to structural urologic anomalies is frequent in the pediatric population. Impaired bladder function is thought to have a negative effect on graft function and survival. The aim of this study was to present our single-center experience and long-term follow-up results in pediatric patients who underwent renal transplantation for urologic reasons and to compare graft survival among patients who underwent transplantation for nonurologic reasons. METHOD: The paper records of renal transplanted children (<18 years of age) held by Ege University Medical Faculty between 1998 and 2018 were evaluated retrospectively. Patients with normal bladder function who underwent transplantation for urologic reasons were defined as group A, whereas patients who had impaired bladder function and underwent transplantation for urologic reasons were defined as group B; a control group was defined as group C. RESULTS: Eighty-three patients were included in the study. The creatinine values of the patients at their last visit were no different between groups (P = .930). One-, 5-, and 10-year graft survival rates were 97%, 89%, and 74%, respectively, in group A; 100% for all years in group B; and 97%, 94%, and 80%, respectively, in group C. There was no statistically significant difference in terms of graft survival between groups (P = .351). CONCLUSION: Children with end-stage renal disease owing to urologic abnormalities may be good candidates for kidney transplantation with a favorable prognosis for graft function and survival.