RESUMO
BACKGROUND: Post infectious glomerulonephritis is the most common glomerulopathy in children, occurring several weeks after nephritogenic streptococcal throat or skin infection. Reports of acute glomerulonephritis (AGN) occurring during active bacterial pneumonia in children are rare. The aim of this study was to evaluate the incidence of AGN concurrent with bacterial pneumonia in children. METHODS: We reviewed records of all children admitted with a diagnosis of pneumonia to the pediatric department in a single tertiary medical center between January 2015 and April 2023. Patients with bacterial pneumonia and concurrent glomerulonephritis were included. RESULTS: Eleven (0.98%) of 1,123 patients with bacterial pneumonia had concurrent AGN. All were males with a median age of 2.7 years (range 1-13). Mean time from bacterial pneumonia onset to acute glomerulonephritis symptoms was 2.7 ± 1.5 days. Five (45%) patients had evidence of pneumococcal infection. Hypertension was found in 10 (91%) patients. Mean trough eGFR was 43.5 ± 21.4 ml/min/1.73 m2 (range 11-73). Ten patients (91%) had low C3 levels. Median urinary protein-to-creatinine ratio was 2.5 mg/mg (IQR 2.15-14.75). All patients fully recovered. Microscopic hematuria was the last finding to normalize after a median of 29.5 days (IQR 17.25-38). CONCLUSION: AGN during bacterial pneumonia may be more frequent than previously recognized. Kidney prognosis was excellent in all patients. Prospective studies are needed to evaluate the impact of this condition.
Assuntos
Glomerulonefrite , Pneumonia Bacteriana , Criança , Masculino , Humanos , Lactente , Pré-Escolar , Adolescente , Feminino , Glomerulonefrite/complicações , Glomerulonefrite/diagnóstico , Glomerulonefrite/epidemiologia , Rim , Doença Aguda , Pneumonia Bacteriana/complicações , Pneumonia Bacteriana/diagnóstico , Pneumonia Bacteriana/epidemiologia , Testes de Função RenalRESUMO
BACKGROUND: Post-transplantation immunosuppressive therapy reduces the risk of graft rejection but raises the risk of infection and malignancy. A biomarker of the level of immunosuppression can be helpful in monitoring immunosuppressive therapy. Inverse correlation between Torque teno virus (TTV) from the Anelloviridae (AV) family load and immune competence was described in previous studies. The aim of this study was to analyze the association between AV family viruses' kinetics and the risk for graft rejection in the first year after kidney transplantation in children. METHODS: The titers of three genera (TTV, TTMDV, and TTMV) from the AV family were monitored by real-time PCR in consecutive samples from children before and after kidney transplantation. RESULTS: Twenty-one children who underwent kidney transplantation were enrolled. Five out of 21 patients experienced acute graft rejection within a year from transplantation. We found that in patients who experienced graft rejection, the median titers of TTV and total AV titers at 5-6 months post-transplantation were lower than in those who did not. Using a threshold determined by ROC analysis, significant differences in TTV and total AV load were found between patients who had or did not have graft rejection (p = 0.002 and 0.004, respectively). No association was found between the dominance of any AV genus titer and the likelihood of rejection. CONCLUSION: This pilot study suggests that children after kidney transplantation with low TTV and total AV titers 5-6 months post-transplantation are at increased risk for graft rejection within a year after transplantation. A higher resolution version of the Graphical abstract is available as Supplementary information.
Assuntos
Anelloviridae , Transplante de Rim , Torque teno virus , Criança , DNA Viral , Rejeição de Enxerto , Humanos , Transplante de Rim/efeitos adversos , Projetos Piloto , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Torque teno virus/genética , Carga ViralRESUMO
BACKGROUND: Acid-base balance is maintained by kidney excretion of titratable acids and bicarbonate reabsorption. Metabolic alkalosis is uncommon in dialysis-treated patients. The aim of this retrospective study was to assess the rate of metabolic alkalosis in pediatric patients treated with peritoneal dialysis. METHODS: Medical records of children treated with peritoneal dialysis in Shaare Zedek Medical Center from January 2000 to June 2021 were reviewed and compared with young adults currently treated with peritoneal dialysis. Demographic, clinical, and peritoneal dialysis characteristics were extracted from the medical records. RESULTS: Thirty chronic peritoneal dialysis patients were included in our study, seven under 2 years, 13 between 2 and 18 years, and 10 adults. 90.3% of the measurements in infants showed metabolic alkalosis compared to 32.3% in the 2-18-year group and none in the adult group. Higher size-adjusted daily exchange volume, lack of urine output, and high lactate-containing dialysate were associated with metabolic alkalosis. Alkalosis was not explained by vomiting, diuretic therapy, or carbonate-containing medications. High transport membrane, low dietary protein, and malnutrition, all previously reported explanations for metabolic alkalosis, were not found in our study. CONCLUSIONS: Metabolic alkalosis is common in infants treated with peritoneal dialysis as opposed to older children and adults. High lactate-containing dialysate is a possible explanation. Higher size-adjusted daily dialysate exchange volume, which may reflect higher bicarbonate absorption, is another independent predictor of alkalosis. Acid-base status should be closely followed in infants, and using a dialysis solution with lower bicarbonate or lactate level should be considered. A higher resolution version of the graphical abstract is available as Supplementary Information.
Assuntos
Alcalose , Diálise Peritoneal , Adolescente , Alcalose/etiologia , Bicarbonatos , Criança , Soluções para Diálise , Humanos , Lactente , Ácido Láctico , Diálise Peritoneal/efeitos adversos , Diálise Renal , Estudos RetrospectivosRESUMO
BACKGROUND: Genetic kidney diseases contribute a significant portion of kidney diseases in children and young adults. Nephrogenetics is a rapidly evolving subspecialty; however, in the clinical setting, increased use of genetic testing poses implementation challenges. Consequently, we established a national nephrogenetics clinic to apply a multidisciplinary model. METHODS: Patients were referred from different pediatric or adult nephrology units across the country if their primary nephrologist suspected an undiagnosed genetic kidney disease. We determined the diagnostic rate and observed the effect of diagnosis on medical care. We also discuss the requirements of a nephrogenetics clinic in terms of logistics, recommended indications for referral, and building a multidisciplinary team. RESULTS: Over 24 months, genetic evaluation was completed for a total of 74 unrelated probands, with an age range of 10 days to 72 years. The most common phenotypes included congenital anomalies of the kidneys and urinary tract, nephrotic syndrome or unexplained proteinuria, nephrocalcinosis/nephrolithiasis, tubulopathies, and unexplained kidney failure. Over 80% of patients were referred due to clinical suspicion of an undetermined underlying genetic diagnosis. A molecular diagnosis was reached in 42/74 probands, yielding a diagnostic rate of 57%. Of these, over 71% of diagnoses were made via next generation sequencing (gene panel or exome sequencing). CONCLUSIONS: We identified a substantial fraction of genetic kidney etiologies among previously undiagnosed individuals which influenced subsequent clinical management. Our results support that nephrogenetics, a rapidly evolving field, may benefit from well-defined multidisciplinary co-management administered by a designated team of nephrologist, geneticist, and bioinformatician. A higher resolution version of the Graphical abstract is available as Supplementary information.
Assuntos
Testes Genéticos , Nefropatias , Criança , Humanos , Nefropatias/genética , Fenótipo , Encaminhamento e Consulta , Sequenciamento do Exoma/métodosRESUMO
AIM: Blood culture contamination (BCC) can cause unnecessary hospitalisations and inappropriate use of antibiotics. The aim of this study was to find risk factors associated with BCCs in children and to compare contamination rates between open and closed blood culture collection systems. METHODS: Data were prospectively collected regarding blood cultures obtained in the paediatric emergency department from February 26, 2020, to September 30, 2020, based on the method of drawing blood reported by the obtaining physician. A comparison between contaminated and non-contaminated blood cultures was performed. We also compared the composition of the contaminations in the study period to the same period in 2019. RESULTS: A total of 512 blood cultures were included, 33 (6.4%) of which were contaminated. The only parameter that was associated with an increased rate of contamination by 2.34 fold (95% CI 1.1-4.99, P = 0.028) was obtaining blood through an 'open' system, using a syringe connected to a needle in order to draw blood from an open ended needle. The proportion of contaminations originating from oral flora decreased in the study period by 44.7% as compared to the same period in the previous year (13% vs. 23.5%, P = 0.056). CONCLUSIONS: 'Open system' method, which is commonly used in paediatric emergency departments for blood culture obtainment, was associated with an increase in BCC. Adherence to blood cultures obtainment guidelines, even at the price of two different blood tests, is important in order to reduce BCC rates in children.
Assuntos
Hemocultura , Coleta de Amostras Sanguíneas , Antibacterianos , Hemocultura/métodos , Coleta de Amostras Sanguíneas/métodos , Criança , Serviço Hospitalar de Emergência , Contaminação de Equipamentos , HumanosRESUMO
PURPOSE: The etiology of calcium-oxalate kidney stone formation remains elusive. Biallelic mutations in HOGA1 are responsible for primary hyperoxaluria type 3 and result in oxalate overproduction and kidney stone disease. Our previous study showed that carriers of HOGA1 mutations have elevated urinary levels of oxalate precursors. In this study we explored the possibility that mutations in HOGA1 confer a dominant phenotype in the form of kidney stone disease or hyperoxaluria. MATERIALS AND METHODS: An observational analytic case control study was designed to determine the prevalence of pathogenic HOGA1 mutations among adults with calcium-oxalate kidney stone disease. Given the high prevalence of HOGA1 mutations among Ashkenazi Jews, this group was evaluated separately. Carrier frequency of any of the 52 reported pathogenic mutations was compared to data derived from gnomAD for the corresponding ethnic group. Sanger sequencing of HOGA1 gene was performed on DNA samples from the following groups: 60 Ashkenazi Jews and 86 nonAshkenazi calcium-oxalate stone formers, 150 subjects with low and 150 with high urinary oxalate levels. RESULTS: The carrier prevalence of pathogenic mutations among the Ashkenazi Jews was 1.7% compared to 2.8% in the corresponding control group (p=0.9 OR=0.6 95% CI 0.01-3.51). We did not detect any mutation among the nonAshkenazi study group. No correlation was detected between hyperoxaluria and HOGA1 variants. CONCLUSIONS: This study shows that mutations in HOGA1 do not confer a dominant phenotype in the form of calcium-oxalate kidney stone disease or hyperoxaluria.
Assuntos
Oxalato de Cálcio , Hiperoxalúria/genética , Cálculos Renais/genética , Mutação , Oxo-Ácido-Liases/genética , Fenótipo , Adulto , Idoso , Oxalato de Cálcio/análise , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Cálculos Renais/química , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Beta-2 microglobulin (ß2mG) is a low-molecular-weight protein that is almost exclusively eliminated through the kidneys. It is freely filtered in the glomeruli and almost completely reabsorbed and degraded in the proximal tubules. Normal urinary ß2mG levels are very low (between 0.04 and 0.22 mg/L). No reference values are known in infants and young children. METHODS: Urinary ß2mG levels were measured in 103 healthy term neonates during the first week of life by nephelometric technology. RESULTS: The average level of urinary ß2mG was 0.65 mg/L (95% confidence interval between 0 and 10.8 mg/L). There was a minor difference between male and female neonates but it did not reach statistical significance. There was no effect of the gestational week, birth weight, or weight loss in the first week of life, on urinary ß2mG levels. CONCLUSIONS: First-week urinary ß2mG levels in healthy term infants were higher than adult levels. Incomplete maturation of kidney tubules in neonates could be a possible explanation. These can now be used in clinical practice and further studies that assess the degree of proximal tubular function in health and disease. Graphical abstract.
Assuntos
Urinálise , Microglobulina beta-2 , Creatinina , Feminino , Humanos , Recém-Nascido , Rim , Glomérulos Renais , Túbulos Renais , Masculino , Valores de Referência , Microglobulina beta-2/urinaRESUMO
BACKGROUND: Systemic oxalosis is a severe complication seen in primary hyperoxaluria type I patients with kidney failure. Deposition of insoluble calcium oxalate crystals in multiple organs leads to significant morbidity and mortality. METHODS: We describe a retrospective cohort of 11 patients with systemic oxalosis treated at our dialysis unit from 1982 to 1998 (group 1) and 2007-2019 (group 2). Clinical and demographic data were collected from medical records. Imaging studies were only available for patients in group 2 (n = 5). RESULTS: Median age at dialysis initiation was 6.1 months (IQR 4-21.6), 64% were male. Dialysis modality was mostly peritoneal dialysis in group 1 and daily hemodialysis in group 2. Bone disease was the first manifestation of systemic oxalosis, starting with the appearance of sclerotic bands (mean 166 days, range 1-235), followed by pathological fractures in long bones (mean 200.4 days, range 173-235 days). Advanced disease was characterized by vertebral fractures with resulting kyphosis, worsening splenomegaly, and adynamic bone disease. Two patients developed pulmonary hypertension, 4 and 8 months prior to their death. Four of 11 patients developed hypothyroidism 0-60 months after dialysis initiation. Only one patient survived after a successful liver-kidney transplantation. Four patients died after liver or liver-kidney transplantation. CONCLUSIONS: This is the first comprehensive description of the natural history of pediatric systemic oxalosis. We hope that our findings will provide basis for a quantitative severity score in future, larger studies.
Assuntos
Doenças Ósseas , Hiperoxalúria Primária , Hiperoxalúria , Falência Renal Crônica , Criança , Estudos de Coortes , Humanos , Hiperoxalúria/complicações , Hiperoxalúria Primária/complicações , Hiperoxalúria Primária/terapia , Falência Renal Crônica/etiologia , Falência Renal Crônica/terapia , Masculino , Diálise Renal/efeitos adversos , Estudos RetrospectivosRESUMO
INTRODUCTION: Approximately a third of men worldwide and over 90% of Israeli men are circumcised. The procedure carries a low rate of complication, mainly including surgical and infectious complications. Urinary tract obstruction (UTO) is a rare complication of circumcision. AIMS: The aim of this study was to define the incidence of UTO following circumcision in the last 20 years and describe the characteristics of the affected babies. METHODS: Study participants were identified from a list consisting of all male babies aged 7-30 days treated at the Shaare Zedek Medical Center during the years 2000-2020. Files of patients with serum creatinine ≥ 1 mg/dl were reviewed. Clinical and laboratory data were collected from patients' records. RESULTS: Ten babies with acute kidney injury due to UTO after circumcision were identified. Average age at admission was 10.1 days (8-13). Only two babies had an uncomplicated postnatal course. The main findings on physical examination were distended abdomen, abdominal wall discoloration and leg edema. Average creatinine on admission was 1.76 mg/dl (1.0-3.28). Additional findings were hyperkalemia 6.2 mEq/L (4.5-7.6) and hyponatremia 125 mEq/L (118-134). All hospitalized patients developed post-obstructive diuresis. Kidney function and laboratory abnormalities completely resolved in all of our patients. There was no evidence of kidney damage in six children with long-term follow up. CONCLUSIONS: UTO with acute kidney injury is a rare severe complication of circumcision. Prompt identification and proper treatment can result in complete resolution of kidney function.
Assuntos
Injúria Renal Aguda , Circuncisão Masculina , Sistema Urinário , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Criança , Hospitalização , Humanos , Incidência , Lactente , MasculinoRESUMO
Urinary tract infections can cause renal damage if not treated promptly. The aim of this study was to examine if prior urine cultures can predict antibiotic susceptibility profile in a subsequent culture, in children with recurrent urinary tract infections. The medical records of all children with at least two episodes of urinary tract infection between 1999-2015 that occurred 2 weeks to 1 year apart were reviewed. Pathogen identity and antibiogram were compared between the two cultures for every patient. One hundred sixty-one cases of recurrent urinary tract infections were identified. Seventy-seven (48%) pairs of cultures grew the same pathogen. However, of these, 31 had an altered biogram. In 53% of the culture pairs, the pathogen in the second culture had a similar or better antibiotic susceptibility profile. We found no statistically significant correlation between the elapsed time between the two cultures and the probability of similar susceptibility profile between them. There was no correlation between antibiogram change and any of the demographic characteristics, including a history of renal transplantation and taking antibiotic prophylactic treatment.Conclusions: Antibiotic susceptibility profile of the pathogen in a prior urinary tract infection did not predict antibiotic susceptibility profile in a subsequent urinary tract infection in our study.What is Known:⢠Children with urinary tract infections often have recurrent infections.⢠Clinicians often use prior urine cultures to choose empirical antibiotic treatment in subsequent infections.What is New:⢠In only 50% of the cases, a subsequent urinary tract infection grows the same pathogen as the 1st urinary tract infection.⢠Even in cultures with the same pathogen growth, antibiogram is often different.
Assuntos
Testes de Sensibilidade Microbiana , Infecções Urinárias/microbiologia , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Recidiva , Estudos Retrospectivos , Fatores de Tempo , Urinálise/métodos , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/urinaRESUMO
Icodextrin is a starch-derived glucose polymer used in peritoneal dialysis dialysate to treat volume overload by increasing ultrafiltration in patients with end-stage renal disease. Reported adverse reactions to icodextrin are mild and rare and mainly consist of skin rash that resolves spontaneously after discontinuation of treatment. We describe a young patient with extreme eosinophilia that appeared with the use of icodextrin, disappeared after its discontinuation, and reappeared after a rechallenge with the drug. The eosinophilia was not associated with peritonitis, was asymptomatic, and fully resolved after discontinuation of the drug. Severe eosinophilia can potentially cause tissue damage in several organs, which would indicate that blood eosinophil count is recommended in routine complete blood counts while icodextrin peritoneal dialysis is being administered.
Assuntos
Soluções para Diálise/efeitos adversos , Eosinofilia/induzido quimicamente , Icodextrina/efeitos adversos , Falência Renal Crônica/terapia , Síndrome Nefrótica/complicações , Líquido Ascítico/citologia , Doenças Assintomáticas , Pré-Escolar , Diagnóstico Diferencial , Soluções para Diálise/química , Eosinofilia/sangue , Humanos , Falência Renal Crônica/etiologia , Masculino , Diálise Peritoneal/efeitos adversos , Diálise Peritoneal/métodos , Peritonite/diagnósticoRESUMO
Tuberous sclerosis complex (TSC) is an autosomal dominantly inherited disorder with variable expressivity associated with hamartomatous tumors, abnormalities of the skin, and neurologic problems including seizures, intellectual disability, and autism. TSC is caused by pathogenic variants in either TSC1 or TSC2. In general, TSC2 pathogenic variants are associated with a more severe phenotype than TSC1 pathogenic variants. Here, we report a pathogenic TSC2 variant, c.1864C>T, p.(Arg622Trp), associated with a mild phenotype, with most carriers meeting fewer than two major clinical diagnostic criteria for TSC. This finding has significant implications for counseling patients regarding prognosis. More patient data are required before changing the surveillance recommendations for patients with the reported variant. However, consideration should be given to tailoring surveillance recommendations for all pathogenic TSC1 and TSC2 variants with documented milder clinical sequelae. © 2017 Wiley Periodicals, Inc.
Assuntos
Alelos , Estudos de Associação Genética , Mutação , Fenótipo , Esclerose Tuberosa/diagnóstico , Esclerose Tuberosa/genética , Proteínas Supressoras de Tumor/genética , Substituição de Aminoácidos , Encéfalo/patologia , Criança , Pré-Escolar , Feminino , Genótipo , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Linhagem , Rabdomioma/diagnóstico , Rabdomioma/genética , Rabdomioma/cirurgia , Índice de Gravidade de Doença , Proteína 2 do Complexo Esclerose TuberosaRESUMO
BACKGROUND: Hypernatremic dehydration is a common and potentially life-threatening condition in children. There is currently no consensus as to the optimal strategy for fluid management. OBJECTIVES: To describe the relationship between the type, route and rate of fluids administered and the rate of decline in serum sodium (Na+) concentration. METHODS: We reviewed the medical records of all children under the age of 2 years who were hospitalized with hypernatremic dehydration (serum Na+ ≥ 155 mEq/L) in Shaare Zedek Medical Center during the period 2001-2010. Collected data of 62 subjects included initial and subsequent serum Na+ levels, and rate and Na+ concentration of all intravenous and oral fluids administered until the serum Na+ reached ≤ 150 mEq/L. RESULTS: Median initial serum Na+ was 159.5 mEq/L (IQR 157-163, maximal value 170). The median rate of decline in serum Na+ until serum Na+ reached 150 mEq/L was 0.65 mEq/L/hr (IQR 0.45-0.95). Forty-two children received hypotonic oral fluids which accounted for approximately one-quarter of all fluids they received. There was no significant difference in the rate of decline in serum Na+ between those who consumed oral fluids and those who did not. Neither was there a correlation between the rate of IV fluids, receipt of oral fluids or the degree of dehydration, with the rate of decline in serum Na+. No child experienced an apparent short-term adverse outcome. CONCLUSIONS: A cumulative rate of 5.9 mI/kg/hr of IV fluid administration may reduce the serum Na+ by an acceptable rate (0.65 mEq/L/hr). Fluid therapy comprising up to 25% hypotonic oral fluids and 75% IV fluids high in Na+ concentration was not associated with any short-term adverse outcome in our patient population.
Assuntos
Desidratação/terapia , Hidratação/métodos , Hipernatremia/terapia , Sódio/sangue , Administração Intravenosa , Administração Oral , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Israel , Masculino , Estudos Retrospectivos , Sódio/administração & dosagemRESUMO
Primary hyperoxalurias (PH) comprise a group of three distinct metabolic diseases caused by derangement of glyoxylate metabolism in the liver. Recent years have seen advances in several aspects of PH research. This paper reviews current knowledge of the genetic and biochemical basis of PH, the specific epidemiology and clinical presentation of each type, and therapeutic approaches in different disease stages. Potential future specific therapies are discussed.
Assuntos
Predisposição Genética para Doença , Testes Genéticos/métodos , Hiperoxalúria Primária , Nefrolitíase/etiologia , Terapia de Substituição Renal/métodos , Humanos , Hiperoxalúria Primária/diagnóstico , Hiperoxalúria Primária/genética , Hiperoxalúria Primária/terapia , Mutação/genética , Nefrolitíase/diagnóstico , Oxalatos/metabolismo , Transaminases/genéticaRESUMO
BACKGROUND: Infections are an important cause of morbidity and mortality in solid organ transplant recipients. Neutrophils play a crucial role in the initial host defense against bacterial pathogens. Neutropenia is not uncommon after renal transplantation in adults; however, there are scarce published data in children. We conducted a historical cohort study to evaluate the incidence, clinical course, and management of severe neutropenia after renal transplantation in children. METHODS: In a single-center study, we collected clinical and laboratory data on all children (<20 years) who underwent renal transplantation from January 2005 to March 2014. All post-transplantation blood counts were reviewed; the lowest absolute neutrophil count was recorded and correlated with clinical information and other laboratory findings. RESULTS: Of the 72 patients studied, 46 (64%) had at least one episode of neutropenia [absolute neutrophil count (ANC) <1500/µl] during the study period, 16 of whom (22%) had severe neutropenia (ANC < 500/µl), 2-11 months (median, 3.5) after renal transplantation. Work-up for viral infection or malignancy was performed. Initial management included dose decrease and subsequent discontinuation of antimetabolite, stopping co-trimoxazole and valganciclovir. Bone marrow aspiration in four children revealed normal marrow cellularity in all cases, with myelocyte maturational arrest in two. Eight children (11%) were treated with granulocyte colony-stimulating factor (G-CSF) (5 mcg/kg/day) 1-4 doses (median, 2), with excellent response in all and no adverse effects. Eight children presented with fever during severe neutropenia, and were treated with empiric antibiotics. Mycophenolate/azathioprine were resumed in all patients unless contraindicated (pre-existing BK viremia -1, PTLD -1). Recurrence of neutropenia was seen in five patients, only one of whom required further treatment with G-CSF. Graft function was preserved during and after resolution of neutropenia. Post-transplant neutropenia in children is common, and mostly occurs in the first few months. Its etiology is probably primarily a result of the combination of immunosuppressive agents and prophylactic treatment of infections in the early post-transplant period. CONCLUSIONS: Decreasing immunosuppressive or antimicrobial medications carries the risk of acute rejection or infection. Off-label treatment with G-CSF may present a safe and effective alternative.
Assuntos
Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Hospedeiro Imunocomprometido , Transplante de Rim/efeitos adversos , Neutropenia/tratamento farmacológico , Neutropenia/epidemiologia , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Neutropenia/imunologiaRESUMO
An uncharacterized multisystemic mitochondrial cytopathy was diagnosed in two infants from consanguineous Palestinian kindred living in a single village. The most significant clinical findings were tubulopathy (hyperuricemia, metabolic alkalosis), pulmonary hypertension, and progressive renal failure in infancy (HUPRA syndrome). Analysis of the consanguineous pedigree suggested that the causative mutation is in the nuclear DNA. By using genome-wide SNP homozygosity analysis, we identified a homozygous identity-by-descent region on chromosome 19 and detected the pathogenic mutation c.1169A>G (p.Asp390Gly) in SARS2, encoding the mitochondrial seryl-tRNA synthetase. The same homozygous mutation was later identified in a third infant with HUPRA syndrome. The carrier rate of this mutation among inhabitants of this Palestinian isolate was found to be 1:15. The mature enzyme catalyzes the ligation of serine to two mitochondrial tRNA isoacceptors: tRNA(Ser)(AGY) and tRNA(Ser)(UCN). Analysis of amino acylation of the two target tRNAs, extracted from immortalized peripheral lymphocytes derived from two patients, revealed that the p.Asp390Gly mutation significantly impacts on the acylation of tRNA(Ser)(AGY) but probably not that of tRNA(Ser)(UCN). Marked decrease in the expression of the nonacylated transcript and the complete absence of the acylated tRNA(Ser)(AGY) suggest that this mutation leads to significant loss of function and that the uncharged transcripts undergo degradation.
Assuntos
Alcalose Respiratória/genética , Hipertensão Pulmonar/genética , Hiperuricemia/genética , Mitocôndrias/enzimologia , Mutação/genética , Insuficiência Renal/genética , Serina-tRNA Ligase/genética , Alcalose Respiratória/patologia , DNA Mitocondrial/genética , Feminino , Humanos , Hipertensão Pulmonar/patologia , Hiperuricemia/patologia , Lactente , Recém-Nascido , Masculino , Linhagem , Polimorfismo de Nucleotídeo Único , Aminoacil-RNA de Transferência/genética , Aminoacil-RNA de Transferência/metabolismo , Insuficiência Renal/patologia , SíndromeRESUMO
BACKGROUND: Central venous catheters are frequently used as access for hemodialysis (HD) in children. One of the known complications is central venous stenosis. Although this complication is not rare, it is often asymptomatic and therefore unacknowledged. Superior vena cava (SVC) stenosis is obviously suspected in the presence of upper body edema, but several other signs and symptoms are often unrecognized as being part of this syndrome. CASE-DIAGNOSIS/TREATMENT: We describe four patients with various manifestations of central venous stenosis and SVC syndrome. These sometimes life- or organ-threatening conditions include obstructive sleep apnea, unresolving stridor, increased intracranial pressure, increased intraocular pressure, right-sided pleural effusion, protein-losing enteropathy and lymphadenopathy. The temporal relationship of these complications associated with the use of central venous catheters and documentation of venous stenosis, together with their resolution after alleviation of high venous pressure, points to a causal role. We suggest pathophysiological mechanisms for the formation of each of these complications. CONCLUSIONS: In patients with occlusion of the SVC, various unexpected clinical entities can be caused by high central venous pressure. As often the etiology is not obvious, a high index of suspicion is needed as in some cases prompt alleviation of the high pressure is mandatory.
Assuntos
Cateterismo Venoso Central/efeitos adversos , Diálise Renal/efeitos adversos , Diálise Renal/instrumentação , Adolescente , Cateteres Venosos Centrais/efeitos adversos , Criança , Constrição Patológica/etiologia , Feminino , Humanos , Recém-Nascido , Necrose do Córtex Renal/complicações , Necrose do Córtex Renal/terapia , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Masculino , Estreitamento Uretral/complicações , Estreitamento Uretral/terapiaAssuntos
Hiperoxalúria Primária/complicações , Falência Renal Crônica/terapia , Diálise Renal , Úlcera Cutânea/etiologia , Criança , Humanos , Hiperoxalúria Primária/diagnóstico , Hiperoxalúria Primária/genética , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/etiologia , Masculino , Úlcera Cutânea/diagnóstico , Dedos do Pé , CicatrizaçãoRESUMO
Introduction: Prematurity is associated with incomplete nephrogenesis and an increased incidence of acute kidney injury, that may increase the risk of future kidney disease, including hypertension, proteinuria and reduced glomerular filtration rate. The aim of this study was to evaluate the risk of hypertension or proteinuria in adolescents born prematurely or small for gestational age, in a nationwide cohort. Methods: The study cohort included potential recruits examined in the Israel Defense Forces (IDF) medical facilities, between November 2005 and October 2018. Clinical and anthropometric data, including blood pressure (BP) measurement, were retrieved from the IDF medical files. Adolescents born between January 1993 and December 2000 had additional data on gestational age at birth, retrieved from the Israeli Ministry of Health database. Results: The study cohort included 513,802 participants, aged 17.3 ± 0.9 years, of whom 48,994 had gestational age data. Adolescents born as very preterm, as extremely preterm infants, those born with very low birthweight (VLBW), or with extremely low birthweight (ELBW) had higher incidence of hypertensive-range BP (55%, 47%, 19% and 12%, respectively). No significant association between birthweight (BW) adjusted to gestational age and hypertension was observed. Within the overweight and obese adolescents, those born with VLBW and ELBW, had further increased hypertensive-range BP rate. Proteinuria was diagnosed in 0.33% of the study cohort, with no significant difference between BW or gestational age categories. Conclusion: Adolescents born with VLBW or as significant preterm were associated with high BP and should be monitored for hypertension development and its potential complications.